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CASE REPORT article

Case report: individualized treatment of advanced breast cancer with the use of the patient-derived tumor-like cell cluster model.

Wenjie Xia

  • 1 General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
  • 2 Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
  • 3 Rehabilitation Medicine Center, Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China

Breast cancer is one of the most common tumors in women. Despite various treatments, the survival of patients with advanced breast cancer is still disappointing. Furthermore, finding an effective individualized treatment for different kinds of patients is a thorny problem. Patient-derived tumor-like cell clusters were reported to be used for personalized drug testing in cancer therapy and had a prediction accuracy of 93%. However, there is still a lack of case reports about its application in the individualized treatment of breast cancer patients. Here, we described four cases of individualized treatment for advanced breast cancer using the patient-derived tumor-like cell cluster model (PTC model). In these four cases, the PTC model showed a good predictive effect. The tumor size was reduced significantly or even disappeared completely through clinical, radiological, or pathological evaluation with the help of the PTC model for selecting an individualized therapy regimen. Furthermore, the drug sensitivity test results of the PTC model were consistent with pathological molecular typing and the actual clinical drug resistance of the patients. In summary, our case report first evaluated the application value of the PTC model in advanced breast cancer, and the PTC model might be used as an efficient tool for drug resistance screening and for selecting a better personalized treatment, although further study is needed to prove the validity and stability of the PTC model in drug screening.

Introduction

Breast cancer is one of the most common tumors, and its incidence rate ranks first in female malignant tumors ( 1 ). Despite various treatments, the survival of patients with advanced breast cancer is still disappointing, and the overall survival (OS) is approximately 31% ( 2 ). Because of the rapid progression of the tumor, it is of great importance to find an effective treatment in time ( 3 ). However, finding an effective individualized treatment for different kinds of patients is a thorny problem ( 4 , 5 ). Some articles reported that patient-derived tumor-like cell clusters could be used for personalized drug testing in cancer therapy and had a prediction accuracy of 93% ( 6 ). However, there is still a lack of case reports about its application in the individualized treatment of breast cancer patients. Here, we described four cases of individualized treatment for advanced breast cancer with the use of the patient-derived tumor-like cell cluster model (PTC model).

To identify the optimum therapy for individualized treatment, a personalized PTC drug testing system was conducted as described in a previous study ( 6 ). Thousands of PTCs were divided into a multiwell chip and were evaluated with different drugs, and it was confirmed that the gene expressions within different wells were highly correlated and PTC gene expressions were consistent with that of the original tumor ( 6 ). In clinical practice, the Response Evaluation Criteria in Solid Tumors (RECIST) is usually used to assess the efficacy of individualized treatment. The PTC model defined a similar method to assess drug efficacy: it first fixed the cutoff value of cell viability and then determined the effective concentrations of different drugs.

First, drug efficacy was assessed by measuring the area of all PTCs in each well. PTCs were photographed and evaluated on days 0 and 7. Only cell clusters with diameters greater than 40 μm when measured at both time points were used to estimate the total area. Moreover, cell viability after the addition of drug A was estimated by the following method:

where S represents the sum of the cluster area in each well, n represents the number of repetitions, and q0, q1 represent the time points (days 0 and 7) when the area is measured. The cell viability of the negative control (pNC) was calculated in the same way and served as a quality control. If pNC was less than 0.9, the PTC test was discarded because PTCs were possibly in the decline phase.

Second, the cutoff value of the PTC model was determined based on the RECIST criteria as described in a previous study ( 6 ). According to the RECIST criteria, the tumor efficacy was divided into two subgroups with 0.7 as the cutoff value, and partial response (PR) or complete response (CR) was regarded as effective, while progressive disease (PD) or stable disease (SD) as otherwise. Accordingly, the drug was regarded as effective if pA<0.7, and the drug was not effective if pA ≥0.7.

Lastly, the effective drug concentration (Ec) of drug A in the PTC model was determined according to its clinical efficacy ( 6 ). The clinical efficacy was assessed in 272 breast cancer patients admitted to Zhejiang Provincial People’s Hospital from 1 January 2014 to 31 December 2020 with neoadjuvant chemotherapy or palliative chemotherapy (details are provided in Supplementary Material Table S1 ). For any precise tumor treatment method, including the PTC model, its predicted drug efficacy rate should be consistent with the patient’s clinical response rate of this drug among patients. In our PTC model, the predicted efficacy rate was determined by the cutoff value of the cell viability and the drug’s Ec. Therefore, after fixing the 0.7 cutoff value, we determined the Ec of a drug as the concentration such that the effective rate in the PTC assay was closest to the overall response rate of this drug in clinical practice which was assessed in 272 breast cancer patients with neoadjuvant chemotherapy or advanced treatment ( Table S2 ). We used the PTC samples of 12 patients as the training cohorts to determine the Ec values of nine drugs. The Ec of all drugs used in this study was determined. Three replications were performed for each drug sample pair ( Figure S1 ).

Because some drugs are dependent on exposure time while others are not, the drug exposure time is uniformly set to 24 h to ensure adequate and uniform exposure time.

Case description

A 37-year-old Chinese woman who was in lactation presented with a red and swollen left-side breast. Examination revealed 20 * 15 cm redness and swelling in the left breast and 4 * 3 cm mass in the upper quadrant of the right breast ( Figure 1A ). Core needle biopsies were performed on bilateral breast masses and revealed invasive ductal carcinoma [immunohistochemistry: left—estrogen receptor (ER) (−), progesterone receptor (PR) (−), human epidermal growth factor receptor 2 (HER2) (1+), Ki67 (+35%); right—ER (−), PR (−), HER2 (1+), Ki67 (+30%)]. Furthermore, positron emission tomography/computed tomography (PET/CT) showed multiple lymph node metastases in the bilateral axilla, left clavicular area, and left upper mediastinum, and her final TNM stage was T4N3M1 ( Figure 2A ). Individualized treatment was screened with the use of the PTC model, and the drug sensitivity results are included in Figure 3 and Figure S2 (details are available in Supplementary Material Table S3 ). Finally, compared with the other treatments, the albumin paclitaxel (125 mg/m 2 ) plus carboplatin (AUC = 2) d1, 8, 1/21d regimen showed a higher killing rate of the tumor cells (47%) and was selected. After six cycles of chemotherapy, the tumor size was reduced obviously ( Figure 1B ), but the drop in platelet count was also significant. Thus, the regimen was adjusted to albumin paclitaxel (260 mg/m 2 , d1, 1/21d) plus capecitabine (150 mg BID, d1–14, 1/21d) for maintenance therapy based on previous drug sensitivity results with the PTC model. After 10 cycles of chemotherapy in total, PET/CT was performed again and indicated a significant reduction of tumor and lymph nodes ( Figure 2B ). Finally, to improve her quality of life, bilateral mastectomy and local rotation skin flap grafting were performed ( Figures 1C, D ). The final pathological results indicated a pathologic complete response (pCR) of the right side, with Miller–Payne (MP) grade 5, and MP grade 3 of the left side, with a residual tumor size of 2.5 * 2 cm. By now, the progression-free survival (PFS) has reached 20 months.

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Figure 1 Evaluation of the therapeutic effect after chemotherapy. (A) A frontal view of the patient first presenting with a red and swollen left-side breast; (B) a frontal view of the redness and swelling of the patient’s left breast decreasing obviously after six cycles of chemotherapy; (C) a frontal view of the patient completing 10 cycles of chemotherapy prior to a planned mastectomy; (D) a frontal view of the patient after bilateral mastectomy and local rotation skin flap grafting.

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Figure 2 PET/CT images evaluating the changes in breast masses and metastatic lymph nodes during treatment in case 1. (A) PET/CT images showing intense FDG uptake in the bilateral breast, bilateral axilla, left clavicular area, and left upper mediastinum at the time of initial diagnosis; (B) PET/CT images showing that areas of high FDG uptake in the breast and lymph nodes were significantly reduced after 10 cycles of chemotherapy.

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Figure 3 The drug sensitivity results of the PTC model for individualized treatment in case 1. (A) Comparison of trastuzumab before and after dosing; (B) comparison of epirubicin + cyclophosphamide before and after dosing; (C) comparison of vinorelbine + capecitabine before and after dosing; (D) comparison of albumin paclitaxel + capecitabine before and after dosing; (E) comparison of albumin paclitaxel + carboplatin before and after dosing; (F) negative control (NC) group.

A 50-year-old Chinese woman presented with a 3 * 2-cm right breast mass. Core needle biopsy indicated invasive ductal carcinoma [immunohistochemistry: ER (−), PR (−), HER2 (3+), Ki67 (+80%)]. In addition, PET/CT showed multiple bone metastases and right axillary lymph node metastasis, and the final stage was T2N1M1. The PTC model was used for drug sensitivity screening ( Figure 4 and Figure S3 ; details are available in Supplementary Material Table S4 ). The PTH (albumin paclitaxel 260 mg/m 2 d1, trastuzumab 8 mg/kg d1 followed by 6 mg/kg d1, and pertuzumab 840 mg d1 followed by 420 mg d1, 1/21d) regimen showed a better tumor cell killing rate of 70% and was finally selected. In addition, zoledronic acid was used to inhibit bone metastasis. After four cycles of chemotherapy, the tumor size was reduced obviously. Finally, right mastectomy and axillary lymph node dissection were performed, and the pathological results indicated a pCR of the tumor with MP grade 5. By now, the PFS has reached 18 months.

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Figure 4 The drug sensitivity results of the PTC model for individualized treatment in case 2. (A) Comparison of albumin paclitaxel + capecitabine + trastuzumab before and after dosing; (B) comparison of albumin paclitaxel + carboplatin + trastuzumab before and after dosing; (C) comparison of albumin paclitaxel + carboplatin before and after dosing; (D) comparison of pyrotinib + capecitabine before and after dosing; (E) comparison of epirubicin before and after dosing; (F) comparison of albumin paclitaxel + trastuzumab + pertuzumab before and after dosing; (G) negative control (NC) group.

A 37-year-old Chinese woman presented with a 2.5 * 1.5-cm left breast mass. Core needle biopsy indicated invasive ductal carcinoma [immunohistochemistry: ER (−), PR (−), HER2 (2+), Ki67 (+30%)]. Fluorescence in-situ hybridization (FISH) was performed and the result was negative. Thus, the EC * 4 (pharmorubicin 90 mg/m 2 plus cyclophosphamide 600 mg/m 2 d1, 1/21d)–T * 4 (docetaxel 100 mg/m 2 d1, 1/21d) regimen was used for neoadjuvant chemotherapy. After eight cycles of neoadjuvant chemotherapy, modified radical mastectomy was performed, and the pathological results revealed invasive ductal carcinoma [MP grade 3, immunohistochemistry: ER (−), PR (−), HER2 (2+), Ki67 (+20%)]. Then, FISH was performed again andthe result was still negative. However, 2 months later, thepatient was confirmed with chest wall metastases [immunohistochemistry: ER (−), PR (−), HER2 (2+), Ki67 (+10%)]. The PTC model was used for drug sensitivity screening ( Figure S4 ), and the results indicated that anti-HER2 therapy was effective. Then, FISH was performed the third time, and the result turned out to be positive. Finally, the PTH (albumin paclitaxel 260 mg/m 2 d1, trastuzumab 8 mg/kg d1 followed by 6 mg/kg d1, and pertuzumab 840 mg d1 followed by 420 mg d1, 1/21d) regimen was selected, and the chest wall metastases disappeared completely. By now, the PFS has reached 12 months.

A 56-year-old woman presented with a 3 * 2-cm right breastmass. A preoperative puncture was performed and showed invasive ductal carcinoma of the right breast (immunohistochemistry: ER (−), PR (−), HER2 (3+), Ki67 (+35%)] and negative axillary lymph node. All organs (including the lungs) showed no signs of metastasis during preoperative evaluation. Therefore, modified radical mastectomy and sentinel lymph node biopsy were performed, and the postoperative pathological report revealed invasive ductal carcinoma of the right breast [2.5 * 2.0 cm, immunohistochemistry: ER (−), PR (−), HER2 (3+), Ki67 (+70%)] and negative sentinel lymph node (0/5). One month later, CT showed multiple pulmonary nodules that had not been detected on preoperative CT and were considered metastatic ( Figure S5A ). Her final TNM stage was T2N0M1. Thus, the PTH (docetaxel 100 mg/m 2 d1, trastuzumab 8 mg/kg d1 followed by 6 mg/kg d1, and pertuzumab 840 mg d1 followed by 420 mg d1, 1/21d) regimen was selected according to the guidelines. However, pulmonary nodules gradually increased and became larger after four cycles of treatment ( Figure S5B ). PET/CT suggested multiple metastatic nodules in both lungs, the largest of which was approximately 9 * 7 mm ( Figure S6A ). Thus, we implemented a PTC drug sensitivity test to screen effective drugs for individualized treatment. All drugs selected for the PTC sensitivity test were selected according to the guidelines and the clinical experience of experienced physicians. Interestingly, the PTC sensitivity test results suggested that compared with chemotherapy combined with targeted therapy, the corresponding chemotherapy regimen alone had similar tumor cell lethality ( Figures S7 , S8 ). This finding also demonstrated that the treatment regimen previously used (the PTH regimen) was ineffective. In addition, the pulmonary nodules were punctured, and the histopathological diagnosis was consistent with lung metastasis from breast cancer [immunohistochemistry: ER (−), PR (−), HER2 (1+), Ki67 (+30%)]. This result suggested that the patient’s HER2 status had changed, being positive in the primary tumor and negative in the metastatic lung nodule. This was consistent with our test results and might explain why targeted therapy based on the PTC sensitivity test was ineffective. Finally, the NCb (vinorelbine 25 mg/m 2 , d1, 8, carboplatin AUC = 2, d1, 8, 1/21d) plus targeted therapy (trastuzumab 6 mg/kg d1, pertuzumab 420 mg d1, 1/21d) regimen was selected based on the PTC drug sensitivity screening results. After four cycles of treatment, the pulmonary nodules almost completely disappeared ( Figures S5C , S6B ). At present, the patient has achieved a PFS time of 14 months.

The leading causes of death in patients with advanced breast cancer are tumor metastasis and drug resistance ( 3 , 7 ). Increasing evidence has indicated that patient-derived tumor models could present human tumor biology and evaluate the potential clinical responses ( 8 – 10 ). Although patient-derived tumor xenografts (PDXs) were reported to be a precise measurement of drug screening, it was difficult to generate sufficient organoids for drug screening within 2 to 3 weeks from small tissue samples ( 6 , 9 , 11 ). To address the defects of previous technologies, the PTC model was emphasized, which could be a method of long-term maintenance and expansion of primary tumor cells in a Matrigel-free condition ( 6 , 12 ), and it was reported as a structural and functional unit which could recapitulate the original tumors according to genotype, phenotype, and drug response within 2 weeks ( 6 ). Furthermore, a previous study has demonstrated that the PTC model in breast cancer can express ER, PR, and HER2 status similar to those of the original tumor ( 6 ). To ensure the accuracy and stability of drug sensitivity, specific culture conditions and an accurate cutoff value of the PTC model were established ( 6 , 13 ). The consistency of PTC cell viability in different wells as well as the consistency between the predicted results of the PTC model and the patient’s clinical response has been demonstrated ( 6 ). Furthermore, the PTC model was proved to be a tool for personalized treatment selection which had a prediction accuracy of 93% ( 6 , 14 ).

Our case report first evaluated the application value of the PTC model in advanced breast cancer and filled in its lack of clinical validation in the individualized treatment of breast cancer. In these four cases of individualized treatment for advanced breast cancer, the PTC model showed a good predictive effect. The tumor size was reduced significantly or even disappeared completely through clinical, radiological, or pathological evaluation with the help of the PTC model for selecting an individualized therapy regimen. Patients who responded to the treatments were reported to have a better OS; thus, the PTC model, which was reported to increase the pCR rate, might have a certain effect on improving the OS ( 15 , 16 ). Furthermore, the drug sensitivity test results of the PTC model were consistent with pathological molecular typing and the actual clinical drug resistance of the patients. For example, the drug sensitivity results of the PTC model showed that anti-HER2 therapy was insensitive to the tumor in case 1, which was pathologically confirmed as triple negative breast cancer, while in case 3, the drug sensitivity results of the PTC model indicated that anti-HER2 therapy was effective to the patient whose first two FISH tests were negative. Finally, it was confirmed that her HER2 status was positive. Moreover, in case 4, the primary tumor was HER2 positive, but the PTC drug sensitivity test results suggested that lung metastases were insensitive to anti-HER2 therapy. The histopathological findings from the biopsy of pulmonary nodules in case 4 finally confirmed that the patient’s HER2 status had changed from positive in the primary tumor to negative in the lung metastasis, which was consistent with the PTC drug sensitivity test results. In addition, the results of the PTC sensitivity test confirmed that the previously used therapeutic regimen was ineffective, suggesting that it had high value in predicting the drug resistance of tumors. Therefore, the PTC model might be used for evaluating the efficacy of chemotherapy and targeted therapy and for estimating pathological molecular typing, and it demonstrated good value in guiding individualized treatment.

In summary, our case report first evaluated the application value of the PTC model in advanced breast cancer, and the PTC model might be used as an efficient tool for drug resistance screening and for selecting a better personalized treatment, although further study is needed to prove the validity and stability of the PTC model in drug screening.

Data availability statement

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving human participants were reviewed and approved by Ethics Committee of Zhejiang Provincial People’s Hospital. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

WJ and WZ conceived the study, collected and analyzed the data, and co-wrote the first draft. HJ and SF evaluated the histopathological findings, and edited the manuscript. JX and JW were directly involved in the treatment of the patient. All authors contributed to the article and approved the submitted version.

This study was supported by the Public Welfare Technology Application Research Project of Zhejiang Province under Grant No. LGF21H160030, Zhejiang Provincial Natural Science Foundation of China together with Zhejiang Society for Mathematical Medicine (No. LSY19F020002), and Medical and Health Science and Technology Project of Zhejiang Province (2021KY061 and 2023KY046).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2022.897984/full#supplementary-material

Supplementary Figure 1 | Drug efficacy concentration (Ec). The determination of Ec was based upon the efficacy rate (ER) closest to the overall response rate (OR).

Supplementary Figure 2 | The summary of fold changes of tumor cells before and after drug dosing in case 1. It indicating albumin paclitaxel+carboplatin regimen showed the highest tumor cells killing rate of 47% in the PTCs model, and anti-HER2 therapy was insensitive to triple negative breast cancer.

Supplementary Figure 3 | The summary of fold changes of tumor cells before and after drug dosing in case 2. Albumin paclitaxel+ trastuzumab+ pertuzumab regimen showing the highest tumor cells killing rate of 70% in the PTCs model.

Supplementary Figure 4 | The summary of fold changes of tumor cells before and after drug dosing in case 3. It indicating anti-HER2 therapy was effective of PTCs model in case 3.

Supplementary Figure 5 | Axial CT lung window demonstrating changes in pulmonary nodules during treatment in Case 4. (A) Axial CT lung window demonstrating multiple pulmonary nodules, which was considered pulmonary metastasis. (B) Axial CT lung window demonstrating pulmonary nodules were markedly enlarged after four cycles of PTH (docetaxel+trastuzumab+pertuzumab) treatment. (C) Axial CT lung window demonstrating that pulmonary nodules almost disappeared after four cycles of NCbPH (vinorelbine+carboplatin+trastuzumab+pertuzumab) treatment, which was based on CTC drug sensitivity test results.

Supplementary Figure 6 | PET/CT images evaluating changes in pulmonary nodules during treatment in Case 4. (A) PET CT image showing intense FDG uptake in bilateral pulmonary nodules after four cycles of PTH treatment. (B) PET CT image showing that the area of high FDG uptake in the lung was almost completely eliminated after four cycles of NCbPH treatment, which was based on CTC drug sensitivity test results.

Supplementary Figure 7 | PTCs drug sensitivity test results for individualized treatment in Case 4. (A) Comparison of trastuzumab before and after dosing; (B) Comparison of PTH(docetaxel+trastuzumab+pertuzumab) before and after dosing; (C) Comparison of albumin paclitaxel+PH (albumin paclitaxel+trastuzumab+pertuzumab) before and after dosing; (D) Comparison of NCb(vinorelbine+carboplatin) before and after dosing; (E) Comparison of NCbPH (vinorelbine +carboplatin +trastuzumab +pertuzumab) before and after dosing; (F) negative control(NC) group. The results indicating that tumor cells were insensitive to anti-HER-2 therapy and PTH regimen, and this was consistent with pathological molecular typing and previous clinical practice in which PTH regimen showed poor efficacy. NCbPH and NCb regimen showing a higher killing rate of tumor cells(61.7% and 60.3%).

Supplementary Figure 8 | Summary of the fold changes in PTCs before and after drug dosing in Case 4.

Supplementary Table 1 | Detailed patient information for evaluating the clinical efficacy.

Supplementary Table 2 | Summary of efficacy and concentrations of drugs used in this study.

Supplementary Table 3 | The detailed data of changes in the number of tumor cells before and after drug dosing in case 1.

Supplementary Table 4 | The detailed data of changes in the number of tumor cells before and after drug dosing in case 2.

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7. Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E, et al. Cell-of-Origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell. (2018) 173(2):291–304 e6. doi: 10.1016/j.cell.2018.03.022

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9. Stewart E, Federico SM, Chen X, Shelat AA, Bradley C, Gordon B, et al. Orthotopic patient-derived xenografts of paediatric solid tumours. Nature. (2017) 549(7670):96–100. doi: 10.1038/nature23647

10. Byrne AT, Alferez DG, Amant F, Annibali D, Arribas J, Biankin AV, et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat Rev Canc (2017) 17(4):254–68. doi: 10.1038/nrc.2016.140

11. Rossi G, Manfrin A, Lutolf MP. Progress and potential in organoid research. Nat Rev Genet (2018) 19(11):671–87. doi: 10.1038/s41576-018-0051-9

12. Ding RB, Chen P, Rajendran BK, Lyu X, Wang H, Bao J, et al. Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics. Nat Commun (2021) 12(1):3046. doi: 10.1038/s41467-021-23379-3

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Keywords: breast cancer, individualized treatment, patient-derived tumor model, drug testing, case report

Citation: Xia W, Chen W, Fang S, Wu J, Zhang J and Yuan H (2022) Case report: Individualized treatment of advanced breast cancer with the use of the patient-derived tumor-like cell cluster model. Front. Oncol. 12:897984. doi: 10.3389/fonc.2022.897984

Received: 16 March 2022; Accepted: 11 October 2022; Published: 31 October 2022.

Reviewed by:

Copyright © 2022 Xia, Chen, Fang, Wu, Zhang and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Hongjun Yuan, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Breast cancer patient experiences through a journey map: A qualitative study

Affiliations.

  • 1 Clinical Psychology and Psychobiology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain.
  • 2 Medical Oncology Department Hospital Universitario Central of Asturias, Oviedo, Spain.
  • 3 Social Psychology and Quantitative Psychology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain.
  • 4 Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain.
  • 5 Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain.
  • 6 Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
  • 7 Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain.
  • 8 Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
  • PMID: 34550996
  • PMCID: PMC8457460
  • DOI: 10.1371/journal.pone.0257680

Background: Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients' lives (physical, emotional, cognitive, social, and spiritual).

Objective: This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey.

Methods: This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach.

Results: The diagnosis and treatment of breast cancer entails a radical change in patients' day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the "new" day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey.

Conclusions: Comprehending patients' experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

Publication types

  • Research Support, Non-U.S. Gov't
  • Breast Neoplasms*
  • Cross-Sectional Studies
  • Neoplasm Recurrence, Local
  • Qualitative Research

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Pathophysiology

Normal physiology of the human breast.

Prior to sexual maturity, male and female breasts are structurally and functionally similar; they are both comprised of small immature nipples, fatty and fibrous tissue and several duct-like arrangements beneath the areola. 

When puberty is underway in males and females, this is where the major structural development occurs. Male breasts remain unchanged due to the lack of high levels of estrogen and progesterone. Females, on the other hand, have significant changes occur due to an assortment of hormones (estrogen, growth hormone, insulin-like growth factor-1, progesterone, and prolactin) (p.739) that cause the female breast to develop into a lactating system. 

  The mature female breast’s foundational unit is the lobe (each breast contains 15-20) a system of ducts which is comprised of and supported by Cooper ligaments. Each lobe is made up of 20-40 lobules (glands that produce milk). The lobules contain alveolar cells, which are complicated spaces lined with epithelial cells that secrete milk and sub-epithelial cells that contract, passing milk into the arrangement of ducts that leads to the nipple (p. 739). 

The lobes and lobules are enclosed and separated by muscle strands and adipose connective tissue which varies in amount depending on weight, genetics, endocrine factors and contributes to the diversity of breast size and shape.

case study of a patient with breast cancer

(Memorial Sloan Kettering Cancer Center)

During the reproductive years, breast tissue undergoes cyclic changes in response to hormonal changes of the menstrual cycle. After menopause, adipose deposits and connective tissue increases, glandular breast tissue becomes involuted, and breasts are reduced in size and form. Due to elevated aromatase (decreases circulating estrogen) there can be an  increase in white adipose tissue inflammation (p.740).

The function of the female breast is primarily to provide a source of nourishment for the newborn; however, breasts are also a source of pleasurable sexual sensation and in Western cultures have become a sexual symbol (p.741).

(McCance, K. L., & Heuther, S. E. (2019). Pathophysiology: The biological basis for disease in adults and children (8th ed., pp.739-741). St. Louis, MO: Mosby.)

Pathophysiology of Breast Cancer 

Except for skin cancer, breast cancer is the most common cancer in American women. Most breast cancer occurs in women older than 50 years. The major risk factors for breast cancer are classified as reproductive, such as nulliparity and pregnancy-associated breast cancer; familial, such as inherited gene syndromes; and environmental and lifestyle, such as hormonal factors and radiation exposure. Some examples of known carcinogenic agents with sufficient evidence in humans that contribute to the development of breast cancer are alcoholic beverages, diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen menopausal therapy, X-radiation and γ-radiation (Rote, 2019). Other important factors are delayed involution of the mammary gland and increased breast density.

Overall, lifetime risk of breast cancer is reduced in parous women compared to nulliparous women, but pregnancy must occur at a young age. The influence of pregnancy on the risk of cancer also depends on family history, lactation postpartum, and overall parity. Breast gland involution after pregnancy and lactation uses some of the same tissue remodeling pathways activated during wound healing. The presence of macrophages in the involuting mammary gland contributes to carcinogenesis. 

Most breast cancers are adenocarcinomas and first arise from the ductal/lobular epithelium as carcinoma in situ. Carcinoma in situ is an early-stage, noninvasive, proliferation of epithelial cells that is confined to the ducts and lobules, by the basement membrane. About 84% of all in situ disease is ductal carcinoma in situ (DCIS); the remainder is mostly lobular carcinoma in situ (LCIS) disease.  Ductal carcinoma in situ (DCIS) refers to a heterogenous group of proliferative lesions limited to ducts and lobules without invasion to the basement membrane. DCIS occurs predominantly in women but can also occur in men. DCIS has a wide spectrum of risk for invasive cancers. Preinvasive lesions do not invariably progress to invasive malignancy. Lobular carcinoma in situ (LCIS) originates from the terminal duct-lobular unit. Unlike DCIS, LCIS has a uniform appearance; thus, the lobular structure is preserved. The cells grow in non-cohesive clusters, typically because of a loss of the tumor-suppressive adhesion protein E-cadherin . Also, unlike DCIS, LCIS is found as an incidental lesion from a biopsy and not mammography, is more likely to be present bilaterally.

(Winslow, 2012)

Breast cancer is a heterogeneous disease with diverse, molecular, genetic, phenotypic, and pathologic changes. Tumor heterogeneity results from the genetic, epigenetic, and microenvironmental influences (selective pressure) that tumor cells undergo during cancer progression. Cellular subpopulations from different sections of the same tumor vary in many ways including growth rate, immunogenicity, ability to metastasize, and drug response, demonstrating significant heterogeneity. The biological attributes of a tumor as a whole are strongly influenced by its subpopulation of cells with cellular populations communicating through paracrine or contact-dependent signaling (juxtacrine) from ligands and mediated from components of the microenvironment such as blood vessels, immune cells, and fibroblasts. 

case study of a patient with breast cancer

Figure 1. Histological special types of breast cancer preferentially oestrogen receptor positive. (A) Tubular carcinoma, (B) cribriform carcinoma, (C) classic invasive lobular carcinoma, (D) pleomorphic invasive lobular carcinoma, (E) mucinous carcinoma, (F) neuroendocrine carcinoma, (G) micropapillary carcinoma, (H) papillary carcinoma, (I) low grade invasive ductal carcinoma with osteoclast-like giant cells. (Weigelt, Geyer, & Reis-Filho, 2010)

case study of a patient with breast cancer

Figure 2. Histological special types of breast cancer preferentially oestrogen receptor negative. (A) Adenoid cystic carcinoma, (B) secretory carcinoma, (C) acinic-cell carcinoma, (D) apocrine carcinoma, (E) medullary carcinoma, (F) metaplastic carcinoma with heterologous elements, (G) metaplastic carcinoma with squamous metaplasia, (H) metaplastic spindle cell carcinoma, (I) metaplastic matrix-producing carcinoma. (Weigelt, Geyer, & Reis-Filho, 2010)

Gene expression profiling studies have identified major subtypes classified as luminal A, luminal B, HER2+, basal-like, Claudin-low, and normal breast. These subtypes have different prognoses and responses to therapy. Tumors can be stratified with gene expression profiles such as Oncotype Dx, Prosigna, and MammaPrint on the basis of genetic profiles. This information helps personalize breast cancer treatment and determine which women need aggressive systemic treatment for high-risk cancers versus close surveillance for indolent tumors.

Many models of breast carcinogenesis have been suggested and the expanding themes include (1) gene addiction, (2) phenotype plasticity, (3) cancer stem cells, (4) hormonal outcomes affecting cell turnover of mammary epithelium, stem cells, extracellular matrix, and immune function. 

Cancer gene addiction includes oncogene addiction, whereby these driver genes play key roles in breast cancer development and progression. In non-oncogene addiction, these genes may not initiate cancer but play roles in cancer development and progression. Examples of key driver genes include HER2 and MYC, and examples of tumor-suppressor genes include TP53, BRCA1, and BRCA2. Once a founding tumor clone is established, genomic instability may assist through the establishment of other subclones and contribute to both tumor progression and therapy resistance. 

Phenotypic plasticity is exemplified by a distinctive phenotype called epithelial-to-mesenchymal transition (EMT) . EMT is involved in the generation of tissues and organs during embryogenesis, is essential for driving tissue plasticity during development, and is hijacked during cancer progression. The EMT-associated programming is involved in many cancer cell characteristics, including suppression of cell death or apoptosis and senescence. It is reactivated during wound healing and is resistant to chemotherapy and radiation therapy. Remodeling or reprogramming of the breast during post-pregnancy involution is important because it involves inflammatory and “wound healing-like” tissue reactions known as reactive stroma or inflammatory stroma . The reactive stroma releases various signals and interleukins that affect nearby carcinoma cells, inducing these cells to activate their previously silent EMT programs. The activation is typically reversible (i.e., plasticity), and those EMT programs may revert through mesenchymal-epithelial (MET) to the previous phenotypic state before the induction of the EMT program. Reactive stroma increases the risk for tumor invasion and may facilitate the transition of carcinoma in situ to invasive carcinoma. Activation of an EMT program during cancer development often requires signaling between cancer cells and neighboring stromal cells. In advanced primary carcinomas, cancer cells recruit a variety of cell types into the surrounding stroma. Overall, increasing evidence suggests that interactions of cancer cells with adjacent tumor-associated stromal cells induce malignant phenotypes.

case study of a patient with breast cancer

Figure 3. Putative EMT and MET in breast cancer progression. Normal epithelial cells undergo a series of transformational changes to become malignant tumor cells. Clonal proliferation of malignant cells gives rise to invasive carcinoma. Some of these cells undergo EMT and enter into the neighboring blood vessels or lymphatic vessels. These cells may remain in the circulation as circulating tumor cells or may extravasate at a distant site. The extravasated tumor cells form macrometastasis by a reverse mechanism known as MET. EMT, epithelial-mesenchymal transition; MET, mesenchymal-epithelial transition. (Liu, Gu, Shan, Geng, & Sang, 2016)

Using a mouse model of tumor heterogeneity, investigators demonstrated different clones within the heterogeneous population had distinct properties, such as the ability to dominate the primary tumor, or to contribute to metastatic populations, or to enter the lymphatic or vascular systems via vascular mimicry. 

case study of a patient with breast cancer

(Wagenblast et al., 2015)

Figure 4. Two adjacent sections of a mouse breast tumor. Tissue at left is stained so that normal blood vessels can be seen (brown arrow). Extending from these vessels are blood filled channels (green arrows). On the right, the tissue is stained for a fluorescent protein expressed by the tumor cells. Here it is seen that blood-filled channels are actually formed by tumor cells in a process known as vascular mimicry.  The team demonstrate that the tumor cells lining these channels help drive metastasis, the process by which tumors spread. (Ravindran, 2019)

Invasion by primary tumor cells typically involves the collective migration of large cohesive groups into adjacent tissue rather than the scattering of individual carcinoma cells. However, still unknown are the precise events occurring at the invasive stage. Dormant carcinoma cells called minimal residual disease (MRD) appear to perpetuate carcinogenesis and form the precursors of eventual metastatic relapse and, sometimes, rapid cancer recurrence. Dormant cells have exited the cell cycle and are not proliferating. Thus current treatments that preferentially kill proliferating cells render dormant cells intrinsically more resistant and may remain after initial chemotherapy, radiotherapy, and surgery. 

Emerging evidence supports three main prerequisites that must be met for metastatic colonization to succeed: the capacity to seed and maintain a population of tumor-initiating stem cells; the ability to create adaptive, organ-specific colonization programs; and the development of a supportive microenvironmental niche. Metastases may also occur early in the process of neoplastic transformation.

case study of a patient with breast cancer

Figure 5 . Extracellular matrix (ECM) changes in breast cancer progression and metastasis. The primary components of the ECM in normal mammary gland are significantly changed in breast cancer. A desmoplastic reaction is associated with breast cancer development, due to the increased production of fibrous ECM by activated fibroblasts and cancer cells. The increased collagen deposition and crosslinking by lysyl oxidase (LOX) enzymes, together with the increased production of fibronectin and other ECM components, stiffens the ECM, which in turn promotes tumor aggressiveness. The basement membrane surrounding the mammary gland epithelium is broken down by ECM remodeling enzymes like MMPs, heparanase and others. Matricellular proteins that promote cancer cell fitness such as tenascin C, periostin, osteopontin, SPARC and thrombospondin-1 are also upregulated. Breast cancer cells from the primary tumor, that include cells with the ability to establish metastatic colonies, enter the blood circulation, disseminate and can reach distant sites. While the vast majority of disseminated cancer cells are eliminated or undergo dormancy due to the adverse environment, few cancer cells are able to resist the selective pressure and establish a metastatic colony. These cells may rely on signals from the ECM such as type I collagen (collagen I), crosslinked by LOX. Tenascin C (TNC) and periostin (POSTN), which are crucial ECM proteins of the metastatic niche, promote stem/progenitor pathways and metastatic fitness in disseminated breast cancer cells. (Insua-Rodríguez & Oskarsson, 2016)

The first clinical manifestation of breast cancer is usually a small, painless lump in the breast. Other manifestations include palpable lymph nodes in the axillae, dimpling of the skin, nipple and skin retraction, nipple discharge, ulcerations, reddened skin, and bone pain associated with bony metastases. 

Treatment is based on the extent or stage of the cancer and includes surgery, radiation, chemotherapy, hormone therapy, and biologic therapy.

(Unless otherwise cited, all pathophysiology information was gathered from Danhausen, Phillippi, & McCance, 2019)

Nursing Case Study for Breast Cancer

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Natasha is a 32-year-old female African American patient arriving at the surgery oncology unit status post left breast mastectomy and lymph node excision. She arrives from the post-anesthesia unit (PACU) via hospital bed with her spouse, Angelica, at the bedside.  They explain that a self-exam revealed a lump, and, after mammography and biopsy, this surgery was the next step in cancer treatment, and they have an oncologist they trust. Natasha says, “I wonder how I will look later since I want reconstruction.”

What assessments and initial check-in activities should the nurse perform for this post-operative patient?

  • Airway patency, respiratory rate (RR), peripheral oxygen saturation (SpO2), heart rate (HR), blood pressure (BP), mental status, temperature, and the presence of pain, nausea, or vomiting are assessed upon arrival. Medication allergies, social questioning (i.e. living situation, religious affiliation), as well as education preference are also vital. An admission assessment MUST include an examination of the post-op dressing and any drains in place. This should be documented accordingly.
  • The hand-off should be thorough and may be standardized. Some institutions have implemented a formal checklist to provide a structure for the intrahospital transfer of surgical patients. Such instruments help to standardize processes thereby ensuring that clinicians have critical information when patient care is transferred to a new team. The nurse should also prepare to provide education based on surgeon AND oncologist guidance

What orders does the nurse expect to see in the chart?

  • Post-op medications, dressing change and/or drain management, strict I&O, no BP/stick on the operative side (rationale is to help prevent lymphedema – Blood pressure (BP) measurement with a cuff on the ipsilateral arm has been posed as a risk factor for the development of LE after-breast cancer therapy for years, regardless of the amount of lymph node excision.)
  • Parameters for calling the surgeon are also important. The nurse should also check for an oncology service consult.

After screening and assessing the patient, the nurse finds she is AAOx4 (awake, alert and oriented to date, place, person and situation). The PACU staff gave her ice due to dry mouth which she self-administers and tolerates well. She has a 20G IV in her right hand. She states her pain is 2 on a scale of 1-10 with 10 being the highest. Her wife asks when the patient can eat and about visiting hours. Natasha also asks about a bedside commode for urination and why she does not have a “pain medicine button”. Another call light goes off and the nurse’s clinical communicator (unit issued cell phone) rings.

The nurse heard in report about a Jackson-Pratt drain but there are no dressing change instructions, so she does not further assess the post-op dressing situation in order deal with everything going on at the moment. She then sits down to document this patient.

Medications ordered in electronic health record but not yet administered by PACU: Tramadol 50 mg q 6 hrs. Prn for mild to moderate pain. Oxycodone 5 mg PO q 4 hrs. Prn for moderate to severe pain (5-7 on 1-10 scale) Fentanyl 25 mcg IV q3hrs. Prn For breakthrough pain (no relieve from PO meds or greater than 8 on 1-10 scale) Lactated Ringers 125 mL/hr IV infusion, continuous x 2 liters Naloxone 0.4-2 mg IV/IM/SC; may repeat q2-3min PRN respiratory rate less than 6 bpm; not to exceed 10 mg

BP 110/70 SpO2 98% on Room Air HR 68bpm and regular Ht 157 cm RR 14 bpm Wt 53 kg Temp 36.°5C EBL 130mL CBC -WNL BMP Potassium – 5.4 mEq/L

What education should be conducted regarding post-op medications?

  • New post-op pain guidelines rely less on patient-controlled analgesia (aka “pain medicine button”) than in previous years. Most facilities will have an approved standing protocol (i.e., “Multimodal analgesia and Opioid Prescribing recommendation” guideline) or standing orders. The patient must be instructed on how to rate pain using facility-approved tools (aka “pain scales”). She should also report any medication-related side effects and reinforce there is a reversal medication in case of an opioid overdose.

What are some medical and/or non-medical concerns the nurse may have at this point? If there are any, should they be brought up to the surgeon?

  • The nurse may request an anti-emetic such as ondansetron 4 mg IV q 6 hrs prn nausea vomiting (N&V) since it is not uncommon post-op for the patient to have N&V. The rate of LR is a little high for such a small patient and could cause electrolyte imbalances. The nurse may also inquire about the oncologist being on the case and ask if the surgeon has discussed reconstruction with the patient yet. She may also want to ask about dressing change orders.

Natasha sleeps through the night with no complaints of pain. Lab comes to draw the ordered labs and the CNA takes vital signs. See below.

CBC HGB 7.2 g/dl HCT 21.6%

BMP Sodium 130 mEq/L Potassium 6.0 mEq/L BUN 5 mg/dL

BP 84/46 SpO2 91% on Room Air HR 109 RR 22 bpm

What should the nurse do FIRST? Is the nurse concerned about the AM labs? AM vital signs? Why or why not?

  • Check the dressing and drain for bleeding (assess the patient). The patient should also sit up and allow staff to check the bed for signs of bleeding. Reinforce the dressing as needed. Record output from the drain (or review documentation of all the night’s drain output). Labs and vital signs indicate she may be losing blood.

Check the dressing and drain for BLEEDING (assess the patient). The patient should also sit up and allow staff to check the bed for signs of bleeding. Reinforce the dressing as needed. Record output from the drain (or review documentation of all the night’s drain output). Labs and vital signs indicate she may be losing blood.

What orders does the nurse anticipate from the surgeon?

  • The nurse should expect an order to transfuse blood for this patient. Also, dressing reinforcement or change instructions are needed in the case of saturation)

How should the nurse address Natasha’s declaration? What alerts the nurse to a possible complication?

  • First, the complication is that “Kingdom Hall” is the site of worship for Jehovah’s Witnesses. They do not accept ANY blood product, not even in emergencies. It is vital the nurse determines the patient’s affiliation and religious exceptions for medical care before moving forward. Next, employ therapeutic communication to elicit more details about Natasha’s concerns. Say things like, “tell me why you think you’re not attractive?” She may discuss reconstruction options or ask the patient to write down specific questions about this option to ask the provider later. Ask about getting family in to provide support. Seek information to give the patient about support groups and other resources available (as appropriate, ie. prosthetics, special undergarments/accessories, etc)

The surgeon orders 1 unit packed red blood cells to be infused. The nurse then goes to the patient to ask about religious affiliation and to discuss the doctor’s order. After verifying that Natasha is not a practicing Jehovah’s Witness, the nurse proceeds to prepare the transfusion.

What is required to administer blood or blood products?

  • First, the patient’s CONSENT is required to give blood products. The nurse must also prepare to stay with the patient for at least the first 15 minutes of the transfusion taking a baseline set of V/S prior to infusion. Then, V/S per protocol (frequent). Education is also required. The patient should report feeling flushed, back or flank pain, shortness of breath, chest pain, chills, itching, hives. Normal saline ONLY for infusion setup and flushing: size IV 20g or higher. Always defer infusion time limits to “per policy” because this can differ vastly

How should the nurse respond to this question?

  • Planning for post-op cancer treatment should have begun prior to the surgery. Ask the patient if she has discussed plans with her oncologist. Refer to any specialist documentation to see if this is mentioned. Remind the patient of the specialist’s assessment and planning information. Reinforce that testing of the tissue may change the course of treatment as well. Provide education AS PER THE PATIENT’S STATED PREFERENCE and/or resources based on what the plan includes (ie. chemotherapy, radiation, further surgery. Continually assess and reassess patient understanding. Include family and/or support with the patient’s approval.

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Jon Haws

This nursing case study course is designed to help nursing students build critical thinking.  Each case study was written by experienced nurses with first hand knowledge of the “real-world” disease process.  To help you increase your nursing clinical judgement (critical thinking), each unfolding nursing case study includes answers laid out by Blooms Taxonomy  to help you see that you are progressing to clinical analysis.We encourage you to read the case study and really through the “critical thinking checks” as this is where the real learning occurs.  If you get tripped up by a specific question, no worries, just dig into an associated lesson on the topic and reinforce your understanding.  In the end, that is what nursing case studies are all about – growing in your clinical judgement.

Nursing Case Studies Introduction

Cardiac nursing case studies.

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Obstetrics Nursing Case Studies

Respiratory nursing case studies.

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Neuro Nursing Case Studies

Mental health nursing case studies.

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Metabolic/Endocrine Nursing Case Studies

Other nursing case studies.

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  • v.26(3); 2021

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A clinical case of diagnosis of breast cancer in patients with family history of BRCA mutations 1

Marzhan aitmagambetova.

1 West Kazakhstan Marat Ospanov Medical University, Kazakhstan

Gaziza Smagulova

Yerbol bekmukhambetov.

2 National Chamber of Health, Esil District, Kazakhstan

Oksana Zavalyonnaya

Anar tulyaeva.

The incidence of breast cancer is growing rapidly worldwide (1.7 million new cases and 600,000 deaths per year). Moreover, about 10% of breast cancer cases occur in young women under the age of 45. The aim of the study was to report a rare case of BRCA 1-mutated breast cancer in a young patient with multiple affected relatives. Breast cancer is due to a genetic predisposition with BRCA1 and BRCA2 representing a significant proportion of families with a very high risk of developing the disease over a lifetime of up to 50–80%.

Case presentation

In this paper we report a case of a 29-year-old woman with a confirmed diagnosis of left breast carcinoma.

Conclusions

Mutations of the BRCA1 gene were revealed in the patient, in two of her sisters, brother and brother’s daughter.

Introduction

Germline mutations in BRCA1 and BRCA2 genes account for genetic predisposition and increased risk of breast and ovarian cancers [ 1 ]. Most hereditary breast and ovarian cancers are due to highly penetrant germline BRCA mutations which are inherited in an autosomal dominant fashion. In these patients, there are frequently several generations of women affected with breast cancer (often premenopausal) and in some families’ ovarian cancer as well. In addition, other BRCA-associated malignancies, such as prostate, male breast, and pancreatic cancer may also be observed [ 2 ]. The Hereditary Breast and Ovarian Cancer (HBOC) syndrome is caused by loss-of-function mutations in the BRCA1 and BRCA2 genes and explains approximately 16% of inherited breast cancers [ 3 ]. Germline deleterious mutations in BRCA1 (17q11) and BRCA2 (13q12–q13) are associated with a substantially increased risk of breast cancer as compared with the general population, with a cumulative lifetime breast cancer risk of 46–60% in BRCA1 carriers and 43–55% in BRCA2 carriers [ 4 – 6 ]. These mutations have a prevalence of 5–10% in the general breast cancer population and up to 10–20% in those patients with triple-negative breast cancer (TNBC) [ 7 – 9 ], and they have been suggested to be responsible for approximately half of all hereditary breast and ovarian cancer cases [ 10 ]. Couch et al. 1996 reported a total of 254 BRCA1 mutations, 132 (52%) of which were unique. These represented mutations entered into a database established by the Breast Cancer Information Core (BIC). A total of 221 (87%) of all mutations or 107 (81%) of the unique mutations are small deletions, insertions, nonsense point mutations, splice variants, and regulatory mutations that result in truncation or absence of the BRCA1 protein. A total of 11 disease-associated missense mutations (5 unique) and 21 variants (19 unique) as yet unclassified as missense mutations or polymorphisms had been detected. Thirty-five independent benign polymorphisms had been described. The most common mutations were 185delAG (113705.0003) and 5382insC (113705.0018), which accounted for 30 (11.7%) and 26 (10.1%), respectively, of all the mutations [ 11 ]. Consistent with the role of BRCA1 and BRCA2 in DNA repair, germline mutations in these genes lead to impaired homologous repair of chromosomal double strand breaks, with at least a five-fold reduction in DNA double strand break repair [ 12 ]. This, subsequently, predisposes patients to chromosomal instability and leads to unique treatment opportunities, including sensitivity to DNA-damaging agents, ionizing radiation, and poly (ADP-ribose) polymerase (PARP) inhibitors [ 13 – 15 ]. Multiple studies have evaluated neoadjuvant chemotherapy in BRCA-mutated breast cancers, specifically focusing on pathologic complete response (pCR) rates, a known surrogate for clinical efficacy and outcome. A larger observational study evaluating pCR rates in BRCA1-positive breast cancer patients found high rates of pCR in patients receiving neoadjuvant cisplatin (pCR in 10 of 12 patients, 83%), substantially higher than pCR rates in BRCA1-mutated breast cancer patients treated with cyclophosphamide, methotrexate, and fluorouracil (CMF, 7%); doxorubicin and docetaxel (AT, 8%); or doxorubicin and cyclophosphamide with and without fluorouracil (FAC, 22%) [ 16 ]. Patients with invasive breast cancer caused by hereditary breast cancer syndromes constitute a unique patient population with individualized, rationally targeted systemic treatment options. The most common syndrome leading to an increased risk of breast cancer, BRCA-related breast cancer syndrome, involves harmful germline mutations in BRCA1 and BRCA2. These patients are particularly sensitive to DNA damaging agents such as platinum agents, as well as to PARP inhibitors, which, by blocking the formation of ADP-ribose polymers at the site of single-strand breaks, prevent recruitment of DNA damage repair [ 17 ]. Other unique therapies tested in BRCA-mutated invasive breast cancer patients include trabectin, given preclinical evidence suggesting specific activity against intact metastatic breast cancer with excisional nucleotide repair or homologous repair by recombination [ 18 ], and lurbinectin, which induces double-strand breaks resulting in activity against platinum-resistant tumors and cell lines deficient in homologous recombination [ 19 ].

We report a rare case of BRCA1-mutated breast cancer in a young patient with multiple affected relatives.

Patient A., 29 years old, Asian (Kazakh), housewife. Diagnosed with carcinoma of the left breast STIIIAT2N2M0. Condition after neoadjuvant chemotherapy (neo-PCT) + bilateral radical mastectomy + radiation therapy.

In September 2016, while breast-feeding the fourth child, she independently found a mass in the left breast. Ultrasonography of the mammary glands in one month revealed nodulation with size 26 × 22 × 17 mm. Further PET-CT ( Fig. 2 ) was performed and a conclusion was: Abnormal growth of metabolic activities observed in the lower part of the left breast and lymph nodes of the left axillary region compatible with malignant structure. Local examination at the time of diagnosis: In the left breast in the lower quadrant — a dense, inactive tumor with the size 3 × 3 cm and in the left axillary region lymph node 1 × 1 cm. Right breast and lymph nodes without pathology. Trepan biopsy of the left breast lump was performed. The result of histology was invasive ductal carcinoma of nonspecific type ( Fig. 1 ).

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PET-CT of the mammary glands

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The pedigree of patient under study

The result of IGH — RE-0B, RP — 2B, HER2Neo — negative, Ki 67 — 60%. The patient received 4 courses of neoadjuvant polichemotherapy (NPCh) with the FEC scheme (dexamethasone 12 mg I/V drip to 100 ml physiological saline solution on day 1, epirubicin 138 mg I/V drip to 100 ml physiological saline solution on day 1, fluorouracil 690 mg I/V drip on day 1, cyclophosphamide 690 mg I/V drip physiological saline solution on day 1). Then the patient received 12 courses of paclitaxel 110 mg I/V per 500 ml of physiological saline solution. After treatment, there was regression. Heredity is burdened. Her older sister died of ovarian cancer at the age of 43. Her father died of lung cancer at the age of 51. Pregnancy — 4; childbirth — 4; abortion — 0.

Considering the family history, the patient underwent medical genetic counseling with informed consent. Peripheral whole blood was taken in a volume of 10 ml. Extraction of DNA from 100 μl of peripheral blood was performed using a set of reagents “Proba-GS-Genetics” (NPO DNA-Tekhnologiya, Russia), according to the manufacturer’s instructions.

Genotyping was performed by real-time polymerase chain reaction (PCR) using the BRCA OncoGenetics kit (including 8 mutations in the BRCA1 genes (mutations 185delAG, 4153delA, 5382insC, 3819delGTAAA, 3875delGTCT, 300T> G (Cysdel-61Gly), 2080 BRCA2 (mutation 6174delT) according to the manufacturer’s instructions. PCR was performed using a DTprime detecting amplifier (NPO DNA-Tekhnologiya, Russia).

The study was carried out in a scientific molecular genetic laboratory at the Marat Ospanov West Kazakhstan Medical University. Conclusion: the study of the DNA sample revealed: heterozygous replacement in the BRCA1 gene mutation 5382incS. The patient after chemotherapy treatment had bilateral subcutaneous mastectomy with axillary lymph node dissection. The result of the final histology — fibrosis in both mammary glands, metastases of the axillary lymph nodes were revealed. Then, a postoperative course of radiation therapy on the linear accelerator “Trubeam” on the left breast and the zone of the regional lymph node was given SOD-46 Gr. when the ROD was 2.0 Gr. Considering the presence of a gene mutation (5382incS) in the patient and her family history, medical and genetic counseling of relatives (mother, brother, sisters and their adult children) was carried out, informed consent was obtained from all members of her family. 8 relatives were examined, in whom 3 mutations were identified. The analysis revealed a similar mutation 5382incS in her own older brother (42 years old) and her own daughter (17 years old), her own second older sister (37 years old). The eldest sister, J., 1975 year of birth. In October of 2015 she was diagnosed with carcinoma of the ovary STIIIT3N1M0. In November 2018 molecular genetic study of mutation of BRCA1 , BRCA2 genes was carried out. Conclusion: in the studied sample in exon 20 of the BRCA1 gene detected 5382incS mutation in a heterozygous state. Despite the treatment, the therapy was unsuccessful, the patient died on 28.11.2018 at the age of 43 years.

Native second eldest sister, A. born in 1981. Discovered BRCA1 mutation 5382incS. She was examined. According to mammography — BI-RADS M2-L2, breast ultrasound — the lump of the left breast, the size of 1.5–2 cm. A puncture of the mass was done, the result of cytology without atypia. Ultrasound of the pelvis — without pathology. The patient is under the supervision of oncologists.

Older brother (G.) born in 1976. BRCA1 mutation 5382 incS was detected. At the time of the medical examination he had no complaints. Tumor marker PSA — 0.3 ng\ml. MRI of the prostate — MRI picture is typical for nodulation of the right prostate. The patient is under observation.

Niece (brother’s daughter) — born in 2002, was similarly examined in January 2019. BRCA1 mutation 5382 insc was detected. According to ultrasound of the pelvis: no structural changes. Breast ultrasound — in the right breast of the upper outer quadrant hypoallergenic formation of 2.0 × 1.2 cm, similar to the left breast 2.9 × 1.9 cm. Fibroadenoma of both mammary glands. A puncture of the formation of mammary glands was performed. The result of cytology without atypia. The patient is under observation.

The pedigree was based on the interview of the patient under study; it is impossible to determine the genetic status of deceased ancestors ( Fig. 2 ).

In the presented case, the patient has luminal B type breast cancer. According to TCGA, breast cancer luminal B is characterized by a high TP53 mutation rate (29%) and a slightly lower mutation rate of the PIK3CA catalytic subunit alpha (29%). The main characteristics of genomic, clinical and proteomic subtypes are as follows: mRNA expression — lower ER cluster; high proliferation; DNA methylation — hypermethylated phenotype for a subset; protein expression — less estrogen signaling; high FOXM1 and MYC; reactive RPPA subtypes; DNA mutations — TP53 (32%); PIK3CA (32%); MAP3K1 (5%) [ 20 ].

Unlike sporadic cancers, up to 10% of all cancers are due to hereditary genetic defects. Hereditary cancer was first described by doctors-researchers A. Warthin and H. Lynch, who detected families predisposed to cancer, which, in turn, led to the identification of hereditary cancer syndromes [ 20 ]. A number of affected families will inherit one allele of the mutated predisposition gene, called the “germ line mutation”, which is hidden in every cell of the body. As a result, hereditary cancers are characterized by 1) early onset cancer, often younger than 50 years at diagnosis compared to an average age of 60 years in the general population, 2) family history of cancer across generations in which cancer types correspond to the tumor spectrum of the syndrome, as confirmed in this clinical case [ 22 ]. Our data are consistent with the research of A. Rathore who showed that mutated BRCA carcinoma is found in young people with a family history of the disease [ 23 ]. In our case, four out of six children were found to have a mutation in the BRCA1 gene, and two generations were found to have this mutation. One family member died of ovarian cancer. This patient developed the disease at early age. Other family members have a benign formation. However, at the insistence of the family members themselves, we are not talking about the preventive removal of organs. Therefore, they are under careful supervision of oncologists.

Only a relatively small proportion of breast cancers can be explained by the presence of genetic mutations with high penetrance, such as the BRCA1 and BRCA2 genes [ 24 ]. Together with mutations in genes of intermediate penetrance, such as ATM , BARD1 , PALB2 , and CHECK2 , they explain 20–25% of the risk of breast cancer, leaving a significant proportion of heredity that remains to be explained by variants with low penetrance [ 25 ]. Undoubtedly, ongoing research into families with multiple cancer-affected members will lead to the identification of other variants in these genes that also predispose to breast cancer [ 26 ].

Many genes for different populations have been thoroughly studied [ 27 ]. The identified BRCA1 5382insC mutation in our patient was identified at a frequency of 0.13% in the Jewish population [ 28 ], also found in the population of Austria, Slovenia, Germany, Czech Republic, Greece, Denmark, Poland, Latvia, Lithuania, Belarus and Russia [ 10 ]. In Kazakhstan, according to the work of the author B. Apsalikov, out of 250 women, a similar mutation was found in 23. This indicates the occurrence of this mutation in our population [ 29 ]. But all this still requires further large-scale research.

In addition, molecular genetic testing is becoming an important tool for predicting drug reactions, as new target therapeutic agents, such as poly inhibitors, appear and platinum-based sensitivity is reported [ 30 ]. In our case, the patient was prescribed 12 courses of paclitaxel and there was a significant regression of the tumor, which was confirmed by the instrumental study.

Given that BRCA1 and BRCA2 were identified more than 20 years ago, preventive mastectomy remains the gold standard, mutation carriers have strong preferences for chemoprophylaxis [ 31 ]. The patient underwent bilateral subcutaneous mastectomy with lymph node dissection.

The Cancer Genome Atlas (TCGA), a landmark program in the genomics of cancer, has molecularly characterized over 20,000 primary cancers and matched normal samples covering 33 cancers. This collaborative effort between the National Cancer Institute and the National Human Genome Research Institute began in 2006 and brought together researchers from different disciplines and multiple institutions.

Over the next ten years, TCGA generated over 2.5 petabytes of genomic, epigenomic, transcriptomic, and proteomic data. Data that have already improved our ability to diagnose, treat, and prevent cancer [ 32 ]. We compared the results of the presented case with the TCGA data. TCGA identified PIK3CA, the alpha catalytic subunit of PI3K, as the most common SMG in breast lumen cancer, occurring at 45% and 29% rates in the lumen A and lumen B subtypes, respectively. Often these are missense mutations that are grouped in the helical domain and the kinase domain of PI3 kinase and are capable of causing cellular transformation when introduced into mammary epithelial cells [ 33 ].

The TP53 gene product is a potent tumor suppressor that induces apoptosis or cell cycle arrest in response to cellular stress. A mutation in the TP53 gene is a characteristic feature of basal-like breast cancer. In ER+ breast cancer, TP53 mutation is less common (30% in lumen B and 12% in lumen A) [ 34 , 35 ].

The national integrated cancer control network (NCCN) has established guidelines for testing BRCA mutations and for treating people who have a mutation in the BRCA1\2 genes. As our patient has the early age of developing the disease, family history, we used the principles of this guide. NCCN has published recommendations for observing women with positive test for one of the BRCA mutations [ 31 ]. Guided by the principle of NCCN, we will observe the relatives of our patient with detected mutations carefully, under strict control.

Acknowledgments

The authors thank the staff of the Medical Center of the West Kazakhstan Medical University named after Marat Ospanov for providing samples of human blood and the Scientific and Practical Center for the technical assistance provided. The article was written as part of grant funding for a scientific and technical project No. 0118РК01065, the Ministry of Education and Science of the Republic of Kazakhstan and the NAO of the West Kazakhstan Medical University Marat Ospanov.

Conflict of interest

None declared.

The article was written as part of grant funding for a scientific and technical project No. 0118РК01065, the Ministry of Education and Science of the Republic of Kazakhstan and the NAO of the West Kazakhstan Medical University Marat Ospanov.

Author contributions

Conceptualization, M.A. and G.S.; methodology, Y.B.; software, O.Z.; validation, A.T., O.Z. and Y.B.; formal analysis, G.S.; investigation, M.A.; resources, A.T.; data curation, M.A.; writing — original draft preparation, O.Z.; writing — review and editing, A.T.; visualization, Y.B.; supervision, M.A.; project administration, G.S.; funding acquisition, Y.B. All authors have read and agreed to the published version of the manuscript.

Information pertaining to writing assistance

Not applicable.

Ethical disclosure

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Consent for publication

The patients provided written informed consent for the publication of any associated data and accompanying images.

Data sharing statement

Data will be available on request.

  • Introduction
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Scores for the CESD-R range from 0 to 60, with the highest score indicating depression. Scores for the K-PSI-SF range from 36 to 180, with higher scores indicating greater parenting stress.

eTable. Odds Ratio of Gonadotropin-Releasing Hormone Agonist Treatment on the Center for Epidemiologic Studies Depression Score According to Addition of Chemotherapy

eFigure. Distribution of the Child Behavior Checklist (CBCL) Scores of Children of Breast Cancer Patients

Data Sharing Statement

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Shin Y , Kim H , Lee T, et al. Factors in Parenting Stress in Young Patients With Breast Cancer and Implications for Children’s Emotional Development : The PSYCHE Study . JAMA Netw Open. 2023;6(11):e2344835. doi:10.1001/jamanetworkopen.2023.44835

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Factors in Parenting Stress in Young Patients With Breast Cancer and Implications for Children’s Emotional Development : The PSYCHE Study

  • 1 Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
  • 2 Department of Neuropsychiatry, Chamjoeun Hospital, Gyeonggi-do, Korea
  • 3 Department of Psychiatry, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
  • 4 Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea

Question   What factors contribute to parenting stress among mothers with breast cancer, and does maternal breast cancer affect children’s emotional development?

Findings   In this cross-sectional study of 699 females with breast cancer, of whom 499 were mothers, having children, a shorter disease duration, and gonadotropin-releasing hormone treatment were risk factors for depression. Child-related factors were associated with parenting stress, but clinical and treatment–related factors were not correlated.

Meaning   Findings of this study suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that counseling and support tailored to this patient group are imperative.

Importance   The number of patients with breast cancer who have children is substantial. However, the emotional burden of this disease and its implication for childhood development remain largely unknown.

Objective   To investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children’s emotional development.

Design, Setting, and Participants   This cross-sectional study involved a survey of females with stage 0 to 3 breast cancer and was conducted from June 2020 to April 2021 in Seoul, South Korea. Participants were aged 20 to 45 years and completed the Center for Epidemiologic Studies Depression–Revised scale and basic questionnaires on demographic and clinical characteristics. Participants with children completed the Korean Parenting Stress Index Short Form (K-PSI-SF), Child Behavior Checklist, Junior Temperament and Character Inventory, and Children’s Sleep Habits Questionnaire.

Exposure   Having children in patients with breast cancer.

Main Outcomes and Measures   Multivariable logistic and linear regression analyses were performed to investigate the association between maternal depression and parenting stress.

Results   A total of 699 females (mean [SD] age, 39.6 [4.6] years) were included, of whom 499 had children (mean [SD] age of children, 8.0 [2.7] years). Depression was more common in patients with children (odds ratio [OR], 2.25; 95% CI, 1.01-5.05) and patients who had gonadotropin-releasing hormone treatment (OR, 1.68; 95% CI, 1.15-2.44). Disease duration was inversely associated with depression (OR, 0.85; 95% CI, 0.76-0.96). Cancer-related factors were not associated with the K-PSI-SF score. Having children aged 6 years or older (β = 3.09; 95% CI, 0.19-5.99); being the sole primary caregiver (β = −3.43; 95% CI, −5.87 to −0.99); and reporting certain temperament (eg, novelty seeking: β = 0.58; 95% CI, 0.46-0.71), emotional problems (eg, anxious/depressed: β = 8.09; 95% CI, 3.34-12.83), and sleeping pattern (eg, bedtime resistance: β = 0.57; 95% CI, 0.15-0.99) subscale scores in their children were associated with parenting stress. Depression and parenting stress were correlated (β = 0.56; 95% CI, 0.45-0.66; P  < .001). The emotional challenges encountered by children of mothers with breast cancer were not significantly different from reference values.

Conclusions and Relevance   This study found that in patients with breast cancer, child-related factors and depression were significantly associated with parenting stress, but breast cancer–related factors were not correlated. The findings suggest that mothers with breast cancer are susceptible to both depression and parenting stress and that tailored counseling and support are needed.

According to the 2019 National Cancer Registration, breast cancer is the most common cancer among females in South Korea. 1 Furthermore, data from the National Cancer Institute have shown that over 30% of patients with breast cancer younger than 54 years have children younger than 18 years. 2 In East Asia, the proportion of middle-aged patients with breast cancer is higher than that in the US. 3 Consequently, a substantial number of these patients are expected to be the primary caregivers of their children while managing their disease. For mothers with breast cancer, parenting can be challenging, especially during hospitalization or chemotherapy, which can place considerable psychological distress on these patients. Additionally, the children are required to adjust to their mother’s disease and related absence and may also experience anxiety and worries about losing their mother. 4 , 5 Therefore, children may be vulnerable to disrupted emotional development.

Previous research has suggested that maternal breast cancer affects children’s emotional development. 6 - 9 Wellisch et al 6 reported that daughters of mothers with breast cancer had psychological symptoms that were comparable with those of daughters with mothers without a history of the disease, whereas Armsden and Lewis 7 found that children of patients with breast cancer scored higher on behavioral adjustment and lower on self-esteem compared with a control group. In contrast, Howes and colleagues 8 reported no substantial differences in emotional or behavioral problems between children of mothers with vs without breast cancer. Brown et al 9 found similar results, although they highlighted the benefits of emotional support to children’s psychological adjustment. Such inconsistent findings may be attributed to heterogeneity between studies, such as in sample size, clinical outcome assessment methods, and control group composition. 6 - 10

To date, few studies have investigated the emotional problems of children of patients with breast cancer using relevant psychological and clinical scales. Moreover, research into the association of children’s emotional problems and depression with parenting stress of mothers with breast cancer is scarce. Therefore, we aimed to investigate the clinical factors in parenting stress in mothers with breast cancer and the association of maternal depression and parenting stress with their children’s emotional development. Specifically, we examined breast cancer characteristics, treatment, and depression.

This cross-sectional survey included females with stage 0 to 3 breast cancer who visited the breast surgery outpatient clinic at Asan Medical Center in Seoul, South Korea, between June 2020 and April 2021. All participants were aged 20 to 45 years at the time of diagnosis and were currently within 10 years from diagnosis. Patients were excluded from the study if they had (1) recurrent breast cancer; (2) a history of taking psychiatric medications prior to cancer diagnosis, including antipsychotics, antidepressants, and mood stabilizers; (3) an intellectual disability; (4) children with intellectual disabilities, autism spectrum disorders, epilepsy, genetic diseases, or congenital deformities; or (5) children who were not biologically related or older than 12 years. Written informed consent was obtained from all participants. The Asan Medical Center Institutional Review Board approved this cross-sectional study. We followed the Strengthening the Reporting of Observational Studies in Epidemiology ( STROBE ) reporting guideline.

All participants completed questionnaires that identified their demographic and clinical characteristics as well as assessed their depression. Females with children younger than 12 years also completed rating scales that evaluated their own parenting stress and their children’s emotional and behavioral problems, sleeping habits, and temperament.

Each participant’s demographic and clinical characteristics were collected. These characteristics were age; body mass index; history of any diagnosed disease; familial history of cancer; smoking status; marital status; educational level; spouse’s educational level (only for married participants); children’s ages, any diagnosed disease, and primary caregiver (only for participants with children); and self-reported socioeconomic status (high, middle-high, middle-intermediate, middle-low, and low).

Each participant’s medical records were reviewed to identify various cancer-related factors. These factors were disease duration (defined as the interval between diagnosis and treatment initiation), breast cancer clinical stage, presence of BRCA1 and BRCA2 sequence variation, breast surgery type, and other treatment modalities (eg, oophorectomy; radiotherapy [RT]; and systemic treatment, such as chemotherapy, endocrine therapy, or gonadotropin-releasing hormone [GnRH] treatment).

The Center for Epidemiologic Studies Depression–Revised (CESD-R) scale assesses depressive symptoms. 11 We validated and used the Korean version of the CESD-R scale (score range: 0-60, with the highest score indicating depression). 12 We considered a cutoff score of 16 or higher as depression. The Korean Parenting Stress Index Short Form (K-PSI-SF) consists of 36 questions, with a 5-point Likert scale grading 3 domains: parental distress, parent-child dysfunctional interaction, and difficult child. 13 Scores range from 36 to 180, with higher scores indicating greater parenting stress.

The Child Behavior Checklist (CBCL) assesses the emotional and behavioral problems of children and adolescents. 14 , 15 A profile of psychological problems can be described using 8 subscales across 3 dimensions of the CBCL: internalizing, externalizing, and total behavioral problems. For these 3 dimensions, the cutoff T scores are lower than 60 for the normal range, 60 to 63 for the borderline range, and 64 or higher for the clinical range. For the 8 subscales, the cutoff T scores are lower than 65 for the normal range, 65 to 69 for the borderline range, and 70 or higher for the clinical range. A higher CBCL score indicates greater severity of psychosocial problems.

The Junior Temperament and Character Inventory (JTCI) is based on Cloninger’s classification of personality. 16 It measures 4 different temperament types (novelty seeking, harm avoidance, reward dependence, and persistence) and 3 dimensions of character (self-directedness, cooperativeness, and self-transcendence). 17

The Children’s Sleep Habits Questionnaire (CSHQ) screens for major medical and behavioral sleep disorders in children. 18 It comprises 8 subscales: bedtime resistance, sleep duration, parasomnia, sleep-disordered breathing, night wakings, daytime sleepiness, sleep anxiety, and sleep-onset delay. Scores range from 45 to 135, with higher scores indicating sleep disorder.

The association of mother’s breast cancer with their children’s emotional development was assessed by comparison with reference values. Comparisons between patients with and patients without children were conducted using χ 2 or Fisher exact tests for categorical variables and unpaired, 2-tailed t tests or Wilcoxon rank-sum tests for continuous variables. Analysis of variance and Kruskal-Wallis tests were used to compare CESD-R scale and K-PSI-SF scores according to disease duration. Univariable and multivariable logistic regression analyses were performed to examine the correlates of depression among patients with breast cancer, and a CESD-R scale score of 16 or higher was used as the dependent variable. Variables with P  < .10 in the univariable analysis were entered into the multivariable analysis using backward elimination. In addition, univariable and multivariable linear regression analyses using stepwise selection were performed with the K-PSI-SF score as the dependent variable to investigate factors associated with level of parenting stress in patients with children. The proportion of participants who scored in the borderline and clinical ranges on the CBCL was calculated. Given the associations between disease duration and depression and between depression and parenting stress, we analyzed the CESD-R scale and K-PSI-SF scores according to disease duration. Thus, disease duration was categorized into 6 categories: less than 1, 1 to 2, 2 to 3, 3 to 4, 4 to 5, and more than 5 years.

A 2-sided P  < .05 was considered statistically significant. All statistical analyses were performed using SAS, version 9.4 (SAS Institute), and R, version 3.6.1 (R Project for Statistical Computing).

Of the total 699 females with breast cancer enrolled (mean [SD] age, 39.6 [4.6] years), 499 had children (mean [SD] age of children, 8.0 [2.7] years). Among the 499 patients with children, 490 gave birth before being diagnosed with breast cancer and 9 gave birth after breast cancer treatment. Table 1 shows the demographic and clinical characteristics and cancer-related factors between patients with and without children. Patients without children were younger (mean [SD] age, 37.3 [5.9] vs 40.5 [3.6] years; P  < .001), had a lower body mass index (calculated as weight in kilograms divided by height in meters squared; 22.3 [3.3] vs 22.9 [3.6]; P  = .046), and were less likely to have a history of any diagnosed disease (32.5% [65 of 200] vs 43.7% [218 of 499]; P  = .007) than patients with children. Patients without children were more likely to be smokers (4.0% [8 of 200] vs 0.2% [1 of 499]; P  < .001) and to have graduated from college (91.5% [183 of 200] vs 84.0% [419 of 499]; P  = .01). Regarding cancer-related factors, there were no significant differences in disease duration, cancer stage, or BRCA sequence variation between patients with and without children. However, a higher proportion of patients without children had breast-conserving surgery (69.5% [139 of 200] vs 50.7% [253 of 499]; P  < .001) and RT (65.0% [130 of 200] vs 54.3% [271 of 499]; P  = .005) than patients with children. Other treatment modalities, including oophorectomy, and systemic treatments, such as chemotherapy, endocrine therapy, and GnRH treatment, did not differ between the 2 groups.

Table 2 shows the risk factors for depression among patients with breast cancer. Univariable logistic regression analysis indicated that age (odds ratio [OR], 0.95; 95% CI, 0.92-0.99), smoking (OR, 4.50; 95% CI, 1.19-16.97), high school educational level (OR, 1.74; 95% CI, 1.08-2.79), disease duration (OR, 0.82; 95% CI, 0.74-0.92), RT (OR, 0.72; 95% CI, 0.50-1.03), and GnRH treatment (OR, 1.75; 95% CI, 1.22-2.51) were associated with depression ( Table 2 ). Multivariable analysis showed that having children (OR, 2.25; 95% CI, 1.01-5.05), younger age (OR, 0.96; 95% CI, 0.92-0.99), and high school educational level (OR, 1.76; 95% CI, 1.06-2.94) were associated with depression. Among the cancer-related factors, disease duration (OR, 0.85; 95% CI, 0.76-0.96) and GnRH treatment (OR, 1.68; 95% CI, 1.15-2.44) were associated with depression. Among patients with children, the risk of depression was associated with children’s physical illness (OR, 3.30; 95% CI, 1.29-8.42), mother and other family members being primary caregivers (OR, 1.97; 95% CI, 1.16-3.32), GnRH treatment (OR, 1.93; 95% CI, 1.18-3.14), CSHQ–Sleep-Disordered Breathing score (OR, 1.78; 95% CI, 1.17-2.72), and total K-PSI-SF score (OR, 1.06; 95% CI, 1.04-1.07) ( Table 3 ). Chemotherapy had no significant role in the association between GnRH treatment and depression (eTable in Supplement 1 ; P for interaction = .77).

As shown in Table 4 , parenting stress was significantly higher in mothers with children 6 years or older (β = 3.09; 95% CI, 0.19-5.99) than in those with younger children (1.5 to <6 years) as well as in mothers who were the sole primary caregiver rather than in those who shared the role with other family members (β = −3.43; 95% CI, −5.87 to −0.99). The JTCI-measured novelty seeking (β = 0.58; 95% CI, 0.46-0.71) and harm avoidance (β = 0.21; 95% CI, 0.09-0.33) temperament types were directly correlated with the K-PSI-SF score, whereas the reward dependence temperament was inversely correlated with the K-PSI-SF score (β = −0.31; 95% CI, −0.43 to −0.19). The anxious/depressed (β = 8.09; 95% ci, 3.34-12.83), attention problem (β = 6.78; 95% ci, 1.52-12.04), and rule-breaking behavior (β = 7.28; 95% ci, 1.67-12.89) CBCL subscale scores of 65 or higher were directly associated with the K-PSI-SF score. The bedtime resistance (β = 0.57; 95% CI, 0.15-0.99), sleep-onset delay (β = 2.04; 95% ci, 0.19-3.89), and daytime sleepiness (β = 0.72; 95% CI, 0.35-1.09) subscale scores of the CSHQ were also directly correlated with the K-PSI-SF score. Similarly, the total CESD-R scale score was correlated with the K-PSI-SF score (β = 0.56; 95% CI, 0.45-0.66). Other cancer-related factors were not associated with the K-PSI-SF score.

Disease duration was associated with the CESD-R scale score ( Figure , A). Despite the decreasing score pattern similar to that of the CESD-R scale score, the K-PSI-SF score was not associated with CESD-R scale score throughout the disease duration ( Figure , B).

Children of patients with breast cancer did not score higher than the normal score ranges for internalizing, externalizing, and total behavioral problem ( T scores: <64 [92nd percentile] and <60 [84th percentile]) subscales of the CBCL (eFigure in Supplement 1 ). However, more children of patients with breast cancer scored higher on the anxious/depressed ( T score: ≥70 [98th percentile]) and thought problems ( T score: ≥65 [93rd percentile]) subscales than expected based on the CBCL normal ranges.

In this cross-sectional study, we found that parenting stress was associated with depression, and various child-related factors played a role in this association, such as age, temperament, emotional problems, and sleeping patterns. We did not observe an association between the characteristics of breast cancer itself and parenting stress. Having children, a high school educational level, and GnRH treatment were associated with an increased risk of depression among patients with breast cancer. Conversely, older maternal age and a longer disease duration were correlated with a lower risk of depression. Additionally, we found that maternal breast cancer diagnosis and treatment did not have an association with the emotional development of children.

Among cancer-related factors, disease duration and GnRH treatment were associated with maternal depression. Other cancer-related factors, such as breast cancer stage, BRCA1 and BRCA2 sequence variation, and other treatment modalities, were not associated with depression, which is consistent with the findings of previous studies investigating the association between depression and breast cancer. 19 - 21 In line with previous research, 22 - 24 we found that younger age, having a child, and a lower educational level were all independently correlated with depression. In addition, a short disease duration and GnRH treatment were associated with depression, both of which have previously been reported as risk factors for depression in patients with breast cancer. 25 , 26

We found that GnRH treatment was associated with the risk of depression, whereas chemotherapy had no association. Although adverse psychological outcomes of chemotherapy have been previously reported, 27 the present study highlighted the importance of assessing mental status in those undergoing GnRH treatment, regardless of previous chemotherapy. Brunt and colleagues 28 reported the substantial role of additional ovarian suppression treatment, which was associated with worsened depression and anxiety induced by chemotherapy. However, we found that GnRH treatment alone increased the risk of depression in patients who had not undergone chemotherapy. In general, patients are educated and prepared for chemotherapy prior to treatment, particularly regarding its potential toxic effects; however, such preparation is not common for endocrine therapy. 29 This difference may contribute to distress in patients undergoing endocrine therapy.

We found that maternal depression and parenting stress were correlated. Other studies have also reported an association between maternal depression and parenting stress in various clinical samples. 30 - 32 Given the high prevalence of depression among patients with breast cancer, 33 active surveillance of depression and timely intervention are recommended to reduce psychological distress. In addition, early intervention for mental health issues may be required for children if their mothers with breast cancer are at greater risk of depression.

Results of the present study also revealed that maternal parenting stress was correlated with maternal primary caregiver status and child behavioral problems, sleeping problems, and temperament but was not associated with cancer-related factors. In contrast to previous studies suggesting that maternal parenting stress was highest for mothers with preschool-aged children, 34 we found that patients with children 6 years or older reported higher parenting stress. This finding may be attributed to participants’ limited ability (given their diagnosis and/or treatment) to help their children adjust to school activities. Mothers who were the sole caregiver had significantly higher parenting stress than those who shared caregiving with other family members. Although the presence of additional caregivers was associated with reduced parenting stress, it was also associated with increased risk of depression, which may be attributed to the mother’s relationship with the other caregivers, such as parents or parents-in-law (children’s grandparents). However, we did not analyze these factors because such details were unavailable.

Novelty seeking and harm avoidance in children were directly correlated, whereas reward dependence was inversely correlated, with parenting stress. 35 Novelty seeking represents curiosity and impulsivity, harm avoidance represents anxiousness, and reward dependence represents social contact and devotion. 36 We found that children’s poor sleeping habits (bedtime resistance, sleep-onset delay, and daytime sleepiness) and behavioral problems (anxiety, depression, attention problems, and rule-breaking behaviors) were directly associated with the K-PSI-SF score. Among all clinical variables, these associations were most prominent for the CBCL measures. This finding is consistent with previous research that suggested that child caretaking responsibility 37 and internalizing and externalizing behaviors of children may be factors in higher parenting stress, although this association may be bidirectional. 38 Results of the present study indicated that parenting stress may be more likely to be affected by child-related factors rather than cancer- or treatment-related factors. Thus, when treating mothers with breast cancer, clinicians should pay attention to the children’s mental health and parenting conditions.

Among children of mothers with breast cancer, no remarkable association was noted between child emotional development and maternal breast cancer diagnosis or treatment. Studies investigating the emotional development of these children have reported inconsistent results. John et al 39 reported that children of mothers with breast cancer did not adjust as well as children in the general population in terms of overall quality of life and psychopathological symptoms. In contrast, Armsden and Lewis 7 found that children of mothers with breast cancer had significantly fewer emotional or social problems compared with normative data. 7 Billhult et al 40 observed that mothers with breast cancer tried to maintain a routine of daily activities for their children. Furthermore, Asbury and colleagues 41 found that patients with breast cancer tended to conceal their depressive mood to protect their children emotionally.

A meta-analysis revealed that maternal depression had implications for children’s emotional development. 42 Therefore, interventions for depression and parenting stress may be beneficial for both patients with breast cancer and their children. 43 One study reported that mothers’ concealment of their breast cancer did not benefit the children. 41 Moreover, maternal diagnosis played a role in adolescent children’s susceptibility to experiencing emotional stress. 44 Therefore, interventions to build solid relationships between patients and their children are crucial. 38 , 45 , 46

The results of this study suggest the importance of identifying high-risk population and psychological intervention to relieve the parenting stress of patients with breast cancer. Further studies are warranted to evaluate the effectiveness of psychological consultation or medication to reduce parenting stress. In addition, because of the cross-sectional study design, it is imperative to evaluate in a separate longitudinal study the implications of maternal breast cancer for children as they continue to mature.

The study has several strengths and limitations. First, there was an imbalance between groups (patients with vs without children) in the number of participants, demographic characteristics, and treatments. Second, this single-center study may limit the generalizability of the results. However, participants received standardized treatment and surveillance. In addition, there was a large sample size and validated questionnaires were used, which are strengths of the study. Third, we did not include children of mothers without breast cancer. Instead, we compared the CBCL profiles of the children of patients with breast cancer with population-based, age- and sex-adjusted normal scores. Fourth, as an inherent feature of a cross-sectional design, this study could not draw a conclusion on potential factors or the directionality of associations between variables.

This cross-sectional study found that among mothers with breast cancer, parenting stress was associated with child-related factors and depression, while no associations were found with breast cancer–related factors. Within this patient population, having children, short disease duration, and GnRH treatment were identified as risk factors for depression. These findings underscored the susceptibility of mothers with breast cancer to both depression and parenting stress, regardless of disease duration, emphasizing the imperative for counseling and support tailored to this patient group. Furthermore, this research highlighted that emotional development of children whose mothers had breast cancer was not significantly different from reference values, which could offer solace to these patients amid the challenges they encounter during their illness.

Accepted for Publication: October 6, 2023.

Published: November 28, 2023. doi:10.1001/jamanetworkopen.2023.44835

Correction: This article was corrected on April 15, 2024, to fix errors in the Corresponding Author section and Author Contributions section.

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Shin Y et al. JAMA Network Open .

Corresponding Authors: Hee Jeong Kim, MD, PhD, Department of Surgery ( [email protected] ), and Hyo-Won Kim, MD, PhD, Department of Psychiatry ( [email protected] ), University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

Author Contributions: Dr H. J. Kim had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Shin and H. Kim contributed equally to this work as co–first authors.

Concept and design: H. Kim, J. Kim, Ko, Son, Ahn, H-W. Kim, H. J. Kim.

Acquisition, analysis, or interpretation of data: Shin, H. Kim, T. Lee, S. Kim, S. Lee, Chung, J. Lee, H.-W. Kim, H. J. Kim.

Drafting of the manuscript: Shin, H. Kim, S. Kim.

Critical review of the manuscript for important intellectual content: T. Lee, S. Lee, J. Kim, Chung, Ko, J. Lee, Son, Ahn, H-W. Kim, H. J. Kim.

Statistical analysis: Shin, S. Kim.

Obtained funding: H. J. Kim.

Administrative, technical, or material support: H. Kim, T. Lee, S. Lee, J. Lee, Son, H. J. Kim.

Supervision: H. Kim, S. Lee, J. Kim, Chung, Ko, Ahn, H-W. Kim, H. J. Kim.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was supported by grant HC20C0135 from the Korea Health Technology Research and Development Project through the Korea Health Industry Development Institute, which is funded by the Ministry of Health & Welfare, Republic of Korea.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

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Peer-reviewed

Research Article

Breast cancer patient experiences through a journey map: A qualitative study

Roles Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliation Clinical Psychology and Psychobiology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain

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Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Writing – original draft, Writing – review & editing

Affiliation Medical Oncology Department Hospital Universitario Central of Asturias, Oviedo, Spain

Roles Resources, Validation, Writing – review & editing

Affiliation Social Psychology and Quantitative Psychology Department, Faculty of Psychology, University of Barcelona, Barcelona, Spain

Affiliation Medical Oncology Department, Hospital Universitario Clínico San Carlos, Madrid, Spain

Affiliation Medical Oncology Department, Complexo Hospitalario Universitario de Ourense, Ourense, Spain

Affiliation Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain

Affiliation Medical Oncology Department, Hospital General Universitario de Elche, Elche, Spain

Affiliation Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain

Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Writing – original draft, Writing – review & editing

  • Laura Ciria-Suarez, 
  • Paula Jiménez-Fonseca, 
  • María Palacín-Lois, 
  • Mónica Antoñanzas-Basa, 
  • Ana Fernández-Montes, 
  • Aranzazu Manzano-Fernández, 
  • Beatriz Castelo, 
  • Elena Asensio-Martínez, 
  • Susana Hernando-Polo, 
  • Caterina Calderon

PLOS

  • Published: September 22, 2021
  • https://doi.org/10.1371/journal.pone.0257680
  • Reader Comments

Registered Report Protocol

21 Dec 2020: Ciria-Suarez L, Jiménez-Fonseca P, Palacín-Lois M, Antoñanzas-Basa M, Férnández-Montes A, et al. (2020) Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol. PLOS ONE 15(12): e0244355. https://doi.org/10.1371/journal.pone.0244355 View registered report protocol

Table 1

Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients’ lives (physical, emotional, cognitive, social, and spiritual).

This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey.

This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach.

The diagnosis and treatment of breast cancer entails a radical change in patients’ day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the “new” day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey.

Conclusions

Comprehending patients’ experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

Citation: Ciria-Suarez L, Jiménez-Fonseca P, Palacín-Lois M, Antoñanzas-Basa M, Fernández-Montes A, Manzano-Fernández A, et al. (2021) Breast cancer patient experiences through a journey map: A qualitative study. PLoS ONE 16(9): e0257680. https://doi.org/10.1371/journal.pone.0257680

Editor: Erin J. A. Bowles, Kaiser Permanente Washington, UNITED STATES

Received: February 17, 2021; Accepted: September 3, 2021; Published: September 22, 2021

Copyright: © 2021 Ciria-Suarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Relevant anonymized data excerpts from the transcripts are in the main body of the manuscript. They are supported by the supplementary documentation at 10.1371/journal.pone.0244355 .

Funding: This work was funded by the Spanish Society of Medical Oncology (SEOM) in 2018. The sponsor of this research has not participated in the design of research, in writing the report, or in the decision to submit the article for publication.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Breast cancer is the most common cancer and the one that associates the highest mortality rates among Spanish women, with 32,953 new cases estimated to be diagnosed in Spain in 2020 [ 1 ]. Thanks to early diagnosis and therapeutic advances, survival has increased in recent years [ 2 ]. The 5-year survival rate is currently around 85% [ 3 , 4 ].

Though high, this survival rate is achieved at the expense of multiple treatment modalities, such as surgery, chemotherapy, radiotherapy, and hormone therapy, the side effects and sequelae of which can interfere with quality-of-life [ 5 ]. Added to this is the uncertainty surrounding prognosis; likewise, life or existential crises are not uncommon, requiring great effort to adjust and adapt [ 6 ]. This will not only affect the patient psychologically, but will also impact their ability to tolerate treatment and their socio-affective relations [ 7 ].

Several medical tests are performed (ultrasound, mammography, biopsy, CT, etc.) to determine tumor characteristics and extension, and establish prognosis [ 8 ]. Once diagnosed, numerous treatment options exist. Surgery is the treatment of choice for non-advanced breast cancer; chemotherapy, radiotherapy, and hormone therapy are adjuvant treatments with consolidated benefit in diminishing the risk of relapse and improving long-term survival [ 9 ]. Breast cancer treatments prompt changes in a person’s physical appearance, sexuality, and fertility that interfere with their identity, attractiveness, self-esteem, social relationships, and sexual functioning [ 10 ]. Patients also report more fatigue and sleep disturbances [ 11 ]. Treatment side effects, together with prognostic uncertainty cause the woman to suffer negative experiences, such as stress in significant relationships, and emotions, like anxiety, sadness, guilt, and/or fear of death with negative consequences on breast cancer patients’ quality-of-life [ 10 , 12 ]. Once treatment is completed, patients need time to recover their activity, as they report decreased bodily and mental function [ 13 ], fear of relapse [ 14 ], and changes in employment status [ 15 ]. After a time, there is a risk of recurrence influenced by prognostic factors, such as nodal involvement, size, histological grade, hormone receptor status, and treatment of the primary tumor [ 16 ]. Thirty percent (30%) of patients with early breast cancer eventually go on to develop metastases [ 17 ]. There is currently no curative treatment for patients with metastatic breast cancer; consequently, the main objectives are to prolong survival, enhance or maintain quality-of-life, and control symptoms [ 17 , 18 ]. In metastatic stages, women and their families are not only living with uncertainty about the future, the threat of death, and burden of treatment, but also dealing with the existential, social, emotional, and psychological difficulties their situation entails [ 18 , 19 ].

Supporting and accompanying breast cancer patients throughout this process requires a deep understanding of their experiences. To describe the patient’s experiences, including thoughts, emotions, feelings, worries, and concerns, the phrase “patient voice” has been used, which is becoming increasingly common in healthcare [ 20 ]. Insight into this “voice” allows us to delve deeper into the physical, emotional, cognitive, social, and spiritual effects of the patient’s life. This narrative can be portrayed as a “cancer journey", an experiential map of patients’ passage through the different stages of the disease [ 21 ] that captures the path from prevention to early diagnosis, acute care, remission, rehabilitation, possible recurrence, and terminal stages when the disease is incurable and progresses [ 22 ]. The term ‘patient journey’ has been used extensively in the literature [ 23 – 25 ] and is often synonymous with ‘patient pathway’ [ 26 ]. Richter et al. [ 26 ] state that there is no common definition, albeit in some instances the ‘patient journey’ comprises the core concept of the care pathway with greater focus on the individual and their perspective (needs and preferences) and including mechanisms of engagement and empowerment.

While the patient’s role in the course of the disease and in medical decision making is gaining interest, little research has focused on patient experiences [ 27 , 28 ]. Patient-centered care is an essential component of quality care that seeks to improve responsiveness to patients’ needs, values, and predilections and to enhance psychosocial outcomes, such as anxiety, depression, unmet support needs, and quality of life [ 29 ]. Qualitative studies are becoming more and more germane to grasp specific aspects of breast cancer, such as communication [ 27 , 30 ], body image and sexuality [ 31 , 32 ], motherhood [ 33 ], social support [ 34 ], survivors’ reintegration into daily life [ 13 , 15 ], or care for women with incurable, progressive cancer [ 17 ]. Nevertheless, few published studies address the experience of women with breast cancer from diagnosis to follow-up. These include a clinical pathway approach in the United Kingdom in the early 21st century [ 35 ], a breast cancer patient journey in Singapore [ 25 ], a netnography of breast cancer patients in a French specialized forum [ 28 ], a meta-synthesis of Australian women living with breast cancer [ 36 ], and a systematic review blending qualitative studies of the narratives of breast cancer patients from 30 countries [ 37 ]. Sanson-Fisher et al. [ 29 ] concluded that previously published studies had examined limited segments of patients’ experiences of cancer care and emphasized the importance of focusing more on their experiences across multiple components and throughout the continuum of care. Therefore, the aim of this study is to depict the experiences of Spanish breast cancer patients in their journey through all stages of the disease. To the best of our knowledge, there are no studies that examine the experience of women with breast cancer in Spain from diagnosis through treatment to follow-up of survivors and those who suffer a relapse or incurable disease presented as a journey map.

A map of the breast cancer patient’s journey will enable healthcare professionals to learn first-hand about their patients’ personal experiences and needs at each stage of the disease, improve communication and doctor-patient rapport, thereby creating a better, more person-centered environment. Importantly, understanding the transitional phases and having a holistic perspective will allow for a more holistic view of the person. Furthermore, information about the journey can aid in shifting the focus of health care toward those activities most valued by the patient [ 38 ]. This is a valuable and efficient contribution to the relationship between the system, medical team, and patients, as well as to providing resources dedicated to the patient’s needs at any given time, thus improving their quality of life and involving them in all decisions.

Study design and data collection

We conducted a qualitative study to explore the pathway of standard care for women with breast cancer and to develop a schematic map of their journey based on their experiences. A detailed description of the methodology is reported in the published protocol “Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol” [ 39 ].

An interview guide was created based on breast cancer literature and adapted with the collaboration of two medical oncologists, three nurses (an oncology nurse from the day hospital, a case manager nurse who liaises with the different services and is the ‘named’ point of contact for breast cancer patients for their journey throughout their treatment, and a nurse in charge of explaining postoperative care and treatment), and two psycho-oncologists. The interview covered four main areas. First, sociodemographic and medical information. Second, daily activities, family, and support network. Third, participants were asked about their overall perception of breast cancer and their coping mechanisms. Finally, physical, emotional, cognitive, spiritual, and medical aspects related to diagnosis, treatment, and side effects were probed. Additionally, patients were encouraged to express their thoughts should they want to expand on the subject.

The study was carried out at nine large hospitals located in six geographical areas of Spain. To evaluate the interview process, a pilot test was performed. Interviews were conducted using the interview guide by the principal investigator who had previous experience in qualitative research. Due to the Covid-19 pandemic, all interviews were completed online and video recorded with the consent of the study participants for subsequent transcription. Relevant notes were taken during the interview to document key issues and observations.

Participant selection and recruitment

Inclusion criteria were being female, over 18 years of age, having a diagnosis of histologically-confirmed adenocarcinoma of the breast, and good mental status. To ascertain the reality of women with breast cancer, most of the patients recruited (80%) had been diagnosed in the past 5 years. Patients (20%) were added who had been diagnosed more than 5 years earlier, with the aim of improving the perspective and ascertaining their experience after 5 years.

Medical oncologists and nurses working at the centers helped identify patients who met the inclusion criteria. Participants went to the sites for follow-up between December 2019 and January 2021. Eligible women were informed of the study and invited to participate during an in-person visit by these healthcare professionals. Those who showed interest gave permission to share their contact information (e-mail or telephone number) with the principal investigator, who was the person who conducted all interviews. The principal investigator contacted these women, giving them a more detailed explanation of the study and clarifying any doubts they may have. If the woman agreed to participate, an appointment was made for a videoconference.

A total of 21 women agreed to participate voluntarily in this research. With the objective of accessing several experiences and bolstering the transferability of the findings, selection was controlled with respect to subjects’ stage of cancer, guaranteeing that there would be a proportional number of women with cancer in all stages, as well as with relapses.

Data analysis

The data underwent qualitative content analysis. To assure trustworthiness, analyses were based on the system put forth by Graneheim, and Lundman [ 40 ]. Interviews were transcribed and divided into different content areas; units of meaning were obtained and introduced into each content area; meaning codes were extracted and added; codes were categorized in terms of differences and similarities, and themes were created to link underlying meanings in the categories. All members of the research team (core team, two medical oncologists, three nurses and two psycho-oncologists) reviewed the data and triangulated the outcomes between two sources of data: qualitative data from the interview and non-modifiable information, such as sociodemographic (i.e., age, marital status, having children) and clinical (i.e., cancer stage and surgery type) data. Following this process, we reached saturation of the interview data by the time we had completed 21 interviews.

Ethical considerations

This study was performed in accordance with the ethical standards of the Declaration of Helsinki, and its subsequent amendments. The study was approved by the Research Ethics Committee of University of Barcelona (Institutional Review Board: IRB00003099) and supported by the Bioethics Group of the Spanish Society of Medical Oncology (SEOM) 2018 grant. All participants received a written informed consent form that they signed prior to commencing with the interviews and after receiving information about the study.

Patient baseline characteristics

In total, 21 women with a mean age of 47 years (range, 34 to 61) were interviewed. Most of the study population was married (66.7%), had a college education (66.7%), and had 2 or more children (42.9%). All cancer stages were represented, up to 23.8% tumor recurrence, and most of the primary cancers had been resected (95.2%) (see Table 1 ).

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https://doi.org/10.1371/journal.pone.0257680.t001

Description of the breast cancer patient journey

The women diagnosed with breast cancer describe the journey as a process tremendously affected by the different medical stages. Each stage has its own characteristics that condition the experiences, unleashing specific physical, emotional, cognitive, and social processes. Additionally, the patients perceive this entire process as pre-established journey they must undertake to save their life, with its protocols based on the type and stage of cancer.

“ People said to me , ‘What do you think ? ’ and I answered that there was nothing for me to think about because everything is done , I have to go on the journey and follow it and wait to see how it goes” (Patient 6)

Fig 1 displays the various phases of the journey that patients with breast cancer go through; nevertheless, each woman will go through some or others, depending on their type of cancer.

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https://doi.org/10.1371/journal.pone.0257680.g001

Throughout the entire patient journey.

Processes of loss and reinterpretation of the new circumstance . What stands out the most in the process these women go through during the diagnosis and treatment of breast cancer is loss; specifically, the loss of health and a reinterpretation of the new circumstance and the new bodily reality. In the most extreme cases, the loss of health emerges with the fear of death that many women report at the time of diagnosis or during treatment, due to the distress generated. The loss of identity seems to be related to the evolutionary (existential) moment in which the woman is; there are patients who report feelings of disability or loss of attractiveness, or fear of not being able to get pregnant in the future, especially the youngest.

I felt a terrifying fear and thought , “You have cancer you tell yourself , you’re going to die tomorrow .” (Patient 6) I feel like after the hysterectomy , as a woman , I no longer have anything , only the physical . Sure , I look great , but I tell myself that it’s just a shell , the shell I inhabit , because as a woman , I only have one breast left . (Patient 6) At that moment , I had to make the decision that I was no longer going to be a mother . (Patient 14)

Personal change . Most of the women report that with the diagnosis of breast cancer, their life stands still and from that point forward, a different journey begins. The sole focus on this journey is the disease and its implications. During all those months, the patients stop working; they focus on their medical treatments, and reflect a lot on their current situation and on life. Most of the participants state, especially those who have already been discharged, that they know themselves better now; they take better care of themselves, and they enjoy their day-to-day and the small moments more, making the most of their time, with more initiatives and fewer trivial complaints.

Clearly , you’re not the same person you were before; I don’t think she’ll ever come back; your mindset changes completely and I have sequelae from all the treatments . (Patient 1) I re-think wasting energy on lost causes; what’s more , I’ve also learnt to say no . If I’m not in the mood to go somewhere , I just say no . (Patient 7) I take much more advantage of the present now , because you realize that things can change on any given day . (Patient 3)

Trust and appreciation for their physician . Most of the interviewees stated that they fully trusted the doctors who care for them, without question or objection to the treatments proposed. They reported that, as they go forward, they discuss the tests and treatments that are going to be performed, as well as possible side effects. Several stated that they are unaware of the stage of their cancer; similarly, most also do not know the benefits expressed in X% of the treatments. A few of the participants claimed that they did talk in detail about the different types of treatments with their oncologists, that they had sought another opinion, and one of them even reported having decided to stop chemotherapy, which was very hard for her, given her physician’s insistence that she continue.

The truth is that the oncologist didn’t say much about percentages; what she told me were the steps that I had to take; I thoroughly trusted her and she gave me a lot of peace of mind . (Patient 5) I told him , “I’m going to do whatever you tell me to . ” It never occurred to me to dispute whatever the oncologist might tell me . I was willing to do whatever was needed . (Patient 8)

Most of the women, at some point during the interview, state that they are grateful for the care they received and that, within the seriousness of their situation, there is a treatment for their condition.

I am super grateful for the treatment I’ve received and with the doctors assigned to me . (Patient 2) I’m very lucky; I’m only on my second line of treatment for metastasis and I’ve got a lot more ahead of me , but I consider myself lucky and I believe things are going very well . (Patient 20)

Role of the woman . We can see that the women adopt a role of care-givers and managers of their surroundings. They worry about the disease negatively affecting the people around them, which is why they make an effort to manage the family’s activity for when they can’t do it and they try to avoid being a physical burden or cause emotional distress to the people around them.

I was very strong ; I made everything easy for people , but making it very easy , doesn’t mean that it was easy for me , but that I made it easy for everyone . (Patient 8) I didn’t want to worry anyone because that’s just the way I am , I push forward and that’s that . (Patient 5)

Support network . In all cases, the family appears to be one of the elements that is most involved in the disease process. Within the family, the partner deserves special mention. The testimonies in this regard reveal a wide spectrum of possibilities that range from the feeling of having had great support to a lack of attention and understanding that, in many situations, causes the relationship to be strained or to end. Friends tend to appear more occasionally.

I can’t complain about my husband; he was up to the challenge , very attentive toward me and he fully understood how I was feeling ; I felt very supported . (Patient 14) We’ve had a period of a lot of arguing; I’ve had to sit down with him and tell him that life had changed for me . (Patient 18) I had a partner I had lived with for five and a half years and he told me , literally , that he looked at me like a little sister , no longer as a woman , and he left me , and that hurt me tremendously . (Patient 6)

On the other hand, many patients commented on the importance of social media, where they have met people in the same situation as them. They report feeling understood and in good company; likewise, they commented on the importance of being able to share their doubts and get to know about other experiences.

It’s a situation that only someone who has gone through can understand; you can have all the good intentions in the world , but if you haven’t gone through it , you can’t even begin to understand . (Patient 8)

Use of complementary treatments . Most patients follow conventional medical treatment. However, many resort to other disciplines that help them improve their quality-of-life, like dietary changes, getting more exercise than usual, visits to a psychologist or physical therapist, or using other integrative therapies, such as acupuncture, yoga, reiki, flowers of Bach, homeopathy, cannabis, or meditation.

I started to read a whole bunch of books to see what I could do to take care of myself in terms of nutrition and exercise ; you consider everything you can do . (Patient 5)

Diagnosis/unmasking.

This phase encompasses the time from when the woman detects some symptom or goes to a check-up until the medical diagnosis is made. For the woman, this is a time of a series of tests and results. We have observed that the procedures, especially the healthcare professionals that deal with the patients, and the timing vary, depending on the medical center where they are being cared for. Emotionally, this is one of the most complicated stages.

Emotional whirlwind . The wait to obtain test results has a huge emotional impact for the women, given that it is a time of great uncertainty and fear.

An entire month with all the anguish of finding out if you have something . (Patient 3) The worst part is waiting 15 days to find out the magnitude of the tragedy , if it’s throughout your entire body or only in your breast; you go through a brutal emotional whirlwind; the wait is horrible because there’s nothing else you can do , so that anguish that you carry inside is dreadful; it was hell for me . (Patient 10)

Additionally, the interviewees described many other emotions that included fear of death, fear of having no time, feeling of unreality, rage, anger, sadness, avoidance, denial…

The first thing I thought was that I was going to die and that I wouldn’t finish watching my children [grow up]; my father had died of lung cancer 25 years ago . (Patient 9) My only aim was to get back to normal , as if there were nothing wrong . (Patient 4) You have a lot of conflicting feelings; you wish this weren’t happening; you want to run away , but you say , “Where am I going to run to ? ” . (Patient 14)

Impact of medical communication . Several women comment that, when given the diagnosis, they dissociate because of the emotional impact and that they don’t listen to all the information that the medical professional is giving them.

I remember that she talked and talked , but I didn’t know what she was saying until she said , “Isabel , you’re going to be cured , okay ?”. (Patient 9)

During the diagnostic testing, the women are highly sensitive to the healthcare professionals’ words and gestures.

I looked at the face of the person who was doing the mammogram and that’s when I started to imagine the worst . (Patient 20) I say to them , “ But , is there a solution to this ? ” , and they say to me , “Don’t worry , I’m sure there is a solution . ” That “sure” is etched in my mind . (Patient 10)

Communication and managing their surroundings . After the diagnosis, the patients feel that they have to tell the people around them about their situation, especially those closest to them, the family. They all agree on how hard it is to share. Normally, the people it’s hardest to tell are their mother and their children. When they do, they try to put the most positive spin on it possible, in an attempt to keep them from worrying.

You no longer think only about yourself , you think , “Good grief , now I’ve got to tell my mother .” It’s hard . (Patient 16) I wanted to tell my kids the way I say things , always trying to look for the upside , and positive , although it was hard , but , anyway , in the end , it went well . When I finished , my husband told me , “You’ve convinced me that it’s no big deal .” (Patient 9) I told my son , “Son , don’t cry , your mom’s going to get over this , this is nothing .” (Patient 1)

During this period, the women contemplate how their situation will affect their surroundings and they try to organize it as much as possible.

I devoted myself to planning everything , to organizing what to do with my daughter , and to thinking about work , too , how I had left things at work . (Patient 4)

Surgery/cleaning out the cancer.

Uncertainty and fear . The participants express that before going into surgery, they are told about the kind of procedure that will be done, but that, depending on what they find and the analysis, it may change. In light of this, they exhibit an enormous feeling of uncertainty and fear. In addition, many voice concern about how the surgery will go.

They tell you conservative surgery , but if we open up and see something we didn’t see on the tests , then everything could change . (Patient 10) Aside from the anesthesia , that I’m terrified of , you spend several hours in surgery and you don’t really know how things will go; when they clean it out , they analyze it , and you go into the operating room and you don’t know what can happen . (Patient 9)

Feeling of loss . Considering that the breast is associated with an intimate, feminine part [of their body], many women experience the operation as a loss. This loss is more acute if the operation is a mastectomy and there is no reconstruction at the same time. The loss also involves a loss of identity, compounded by the side effects of chemotherapy, such as hair loss. The interviewees who had undergone mastectomy say that following surgery, when the bandaging is removed and the scar is revealed, is one of the most critical moments, which is why they express difficulty in managing it and appreciate the caring assistance from the professionals.

It is identification with yourself , you know , it’s what you’ve seen in the mirror , what you think you’re like and , suddenly , you’re no longer like that; there’s an incredible personal crisis because you no longer recognize what you’re seeing . (Patient 11) I closed my eyes and I removed the bandaging and I didn’t dare look … with my eyes , I imagined the worst . (Patient 12)

Acceptance or demand for more aggressive intervention . The patients perceive the surgery as essential to recovering their health, which is why the process is widely accepted. Some patients who demand a more invasive intervention, normally a bilateral mastectomy, do so because that way, they feel safer with respect to a possible relapse, as well as more comfortable esthetically.

If they have to remove my breast , let them take it; what I want is to get better . (Patient 16) They say that I am in full remission , so they only removed the lump , but at first , I said that I wanted my whole [breast] removed ; then they assessed how to do it . (Patient 13) They told me that I had a genetic mutation and more possibilities of developing breast cancer and , since I felt such rejection toward my remaining breast , I decided to get rid of that one , too . (Patient 20)

Chemotherapy/loss of identity.

The chemotherapy phase is one of the phases that affects the women’s lives the most, because of its physical impact and how long it lasts. No differences have been found in how they experience chemotherapy depending on whether it was neoadjuvant or adjuvant.

Negative impact of side effects . Chemotherapy is associated with many side effects that vary from one woman to another. Many indicate that they have suffered physical discomfort, such as fatigue, dysgeusia, pain, nausea and vomiting, mucositis, diarrhea, etc.

One day when I didn’t want to go to bed , I went to bed crying because I had the feeling that I wasn’t going to wake up . That day it was because I felt awful . (Patient 1)

Furthermore, all of the women suffer hair loss, which is one of the most-feared effects. Likewise, their body hair also falls out, especially on their face, and their weight fluctuates. All of these changes lead to a loss of identity that is experienced as taking away from their femininity. It must be remembered that oftentimes, chemotherapy is administered after surgery, further exacerbating this physical change. On top of all that, several women comment having to decide at the beginning of treatment whether to freeze their eggs or not; at that moment, many of them forfeit the possibility of becoming a mother or of becoming a mother again, which also adds to this loss of femininity.

Losing my hair was hard , but when it grew out again , I had an identity crisis . I didn’t recognize myself; people said I was really pretty like that , with my hair so short . I looked at myself in the mirror and I said that I’m not that woman , I can see that that woman is pretty , but it’s just that I don’t recognize myself . That’s not me or , it was like , I looked at myself and I didn’t recognize myself . That’s when I suffered a serious identity crisis , psychologically serious , but also serious because I sobbed because I looked at myself , but it wasn’t me . (Patient 6) Where’s that sexy lady , where is she ?, because you don’t feel good . I didn’t like myself at all . I was several sizes larger and I looked at myself and said , “What a monster . ” I didn’t feel good about myself . (Patient 1)

Many patients say that chemotherapy decreases their libido and dries up their mucous membranes, which is why they prefer not to have sex. For those who live as a couple, this situation can strain the relationship.

Sexually , I just didn’t feel like it , I wasn’t in the mood; not only did I not feel like it , my mucous membranes were dry and , what’s smore , I just couldn’t , I couldn’t , I felt bad for my husband , but he said , “Don’t worry .” (Patient 16)

Finally, some interviewees expressed a feeling of being poisoned by the treatment. These women tend to be highly focused on taking care of their body and have a very natural attitude toward life.

I had to really work my awareness that I was poisoning myself; at night I was at home and I thought that all that red liquid was circulating through my veins … I think I even had nightmares . (Patient 4)

Balance between caring for oneself and caring for others . The patients feel that it is time to take care of themselves, so they prioritize resting when they need it. Moreover, they worry about getting a haircut and, most of the times, they look for turbans and wigs. Some also learn how to put on make-up, which they rate as being very positive. On the other hand, those who have children or another person in their care, try to take care of them as much as they are able.

Around 11 : 00 , I no longer felt good , so I’d go to the armchair to rest and it’s like I had an angel , because I’d wake up a minute before I had to set the table and get lunch for my son who would be coming home from school . (Patient 1) While I was getting chemo , I went with the gadget and I told myself , “I’m going to teach you to apply make-up; for instance , your eyelashes are going to fall out . Make a line like this ” and at that moment when you look in the mirror , and we look like Fester in the Addams family . (Patient 13)

Vulnerability . The women experience great uncertainty and feelings of vulnerability the first times they receive chemotherapy, since they don’t know what side effects they will suffer.

With chemo , I started with a lot of fear and , later on , I became familiar with it little by little until the time comes when you go to the hospital like someone who’s going to pick up a bit of paper . (Patient 9)

In addition, those participants who join a social network or who are more closely tied to the hospital setting, know about the relapses and deaths of people around them diagnosed with breast cancer, which makes them feel highly vulnerable.

There are some people who leave the group because … it’s not like there are a lot of relapses and , geez , I think that it messes with your head . (Patient 13) We were almost always the same people at chemotherapy ; there was one guy who was really yellow who looked terrible and , there was one time when we stopped seeing him and another lady asked and the nurse said that he had died . (Patient 15)

At the same time, given the physical changes, especially those that have to do with body hair, many women feel observed when they leave home.

If I have to go out and take off my scarf because I’m hot or go straight out without any scarf on my head and whoever wants to look… let them ; I think that it’s up to us , the patients , to normalize the situation; unfortunately , there are more and more cases . (Patient 9)

Telling the kids . Since when the chemotherapy stage is going to entail many physical changes, the women look for ways to talk to their children about the treatment. Most of them comment that it is a complicated situation and all of them try to talk to their children in such a way as to protect them as much as possible.

I asked the nurse for help before I started chemotherapy to see if she had any pointers about how to talk about this with the kids and she recommended a story , but when I saw it , I didn’t like it … so , in the end , I decided to do it off the cuff . (Patient 10)

Radiotherapy/transition to normality.

The “last” treatment . When the patient reaches radiotherapy, normally, they have already spent several months undergoing physically aggressive medical procedures, which is why they feel exhausted. There is a physical exhaustion resulting from the previous treatments and made worse by the radiation therapy. Furthermore, many women also report feeling emotionally drained by the entire process. However, this is generally accompanied by joy and relief because they feel that they are in the final stage of treatment.

Emotionally , it’s a marathon that has to end up at some point . (Patient 10) For me , radiotherapy was like a lull in the battle , with a winning mind-set . (Patient 4)

Comparison with chemotherapy . There is a widespread perception that radiotherapy has fewer side effects than chemotherapy, although later, when they receive it, several patients suffer discomfort, above all fatigue and dizziness. Several report that at this point, they are mentally worn out and just want to be done with the process, which is why they have less information than about chemotherapy.

I feel like radiotherapy is unknown , that you think it’s more “light ” and it turns out not to be so light . (Patient 13)

Follow-up care/the “new” day-to-day.

Difficulty in getting back to normal . Once the patients are discharged, many feel that they need some time to recover, that it will be slow, in order to restore a more normalized pace of life. They are still working on their emotional and personal process.

When they tell you that you have cancer , they make it very clear : you have a goal; you have some months of chemo , some months of radio , and when you finish , you say , “And now , what do I do ?”. I say that because now I have to get back to my normal life , but I don’t feel normal . I still don’t feel cured , I’m not 100% . And you’re glad you’ve that you’ve finished it all and you’re alive , but at the same time , you say , “Gosh… this is very odd . ” It was a very strange feeling . (Patient 8)

Most patients report that their quality-of-life has diminished, due to the sequelae from the treatments. Lymphedema is one of the sequelae they name most often, although they also mention other symptoms, like digestive upset, weight issues, eye problems, scar pain, etc. The women who are on hormone therapy also suffer side effects, such as joint and muscle pain.

I have lymphedema and , although I have good mobility , I’m a little bit weak; when I go out for dinner , I generally order fish , because I can’t always cut meat well . (Patient 6)

Several interviewees also express difficulty in their affective-sexual relations. Many of them feel insecure because of all the physical changes; others have sequelae that hinder their relations, and still others are suffering symptoms of early menopause. This can cause problems in the couple and for those who don’t have a partner, suffer many complications when it comes to meeting other people.

I haven’t had sex with my husband for 2 years because , it’s also really complicated to get over; I’ve gone for pelvic physical therapy; I’ve used gels , but nothing works . (Patient 8) It’s taken me many months for me to have a relationship again; it’s been really hard because , even though everyone told me that I looked fine , I didn’t feel fine . My breast cancer had taken away all my attributes as a woman . (Patient 6)

Some women also experience difficulties when it comes to returning to work. Several state that they had been fired when they went back. They also report that when interviewing for a job, it’s complicated for them because they have to explain what happened and they mention the schedule of doctor’s visits that they have. Other women comment that they’ve been given early retirement or disability.

You go to the interview and if you tell them that you’ve had the disease , they look at you like you’re a weirdo . (Patient 13)

Breast reconstruction . How reconstruction is experienced, as well as its timing, are highly contingent upon they type of reconstruction. Each one has its pros and cons, but the opinions collected with respect to the type of reconstruction have been positive.

Although it took 18 months for the entire process to be over , I’m delighted with reconstruction with the expander . (Patient 16)

Some patients state that after the whole process, which has been long and complicated, they prefer not to undergo reconstruction immediately. In these cases, they report having felt a subtle pressure from the outside to undergo reconstruction.

Every time I went for my check-ups , they said , “You’re the only one left [who hasn’t undergone reconstruction]” and in the end , the truth is that I’m really happy because I think I look pretty . (Patient 12)

Check-ups and fear of relapse . Check-ups are one of the times that generate most worry and insecurity. The women remark that, starting a few days before and until they receive the results of the follow-up studies, they are more anxious about the possibility of relapse.

At every check-up my legs start shaking again and my stomach is in knots, although at my last one, everything turned out okay and I’m thrilled. (Patient 6) During the first stage , I did everything I had to do and I got over it , but it’s a lottery . You can do whatever you want , but it’s the luck of the draw and when you start going for check-ups , it’s like going to play Russian roulette . (Patient 8)

Maintenance hormone therapy . Hormone therapy is understood differently depending on age and on the major decision of whether or not to be a mother or to have another child. If the woman does not want to have more children, the treatment is accepted better. The patients who take it also report effects derived from menopause, for instance, joint pain or dry mucous membranes.

I did notice joint pain , but since I exercised , [I felt it] much less than my fellow women , although , for instance , when it comes to getting up from a chair , you get up like an old lady . (Patient 10)

Position of support . Several patients mention that, after discharge, they stay active on social media, they volunteer when they find out about someone or to participate in activities related to breast cancer, with the aim of being able to help other people who are in this situation.

It’s really good to meet other people who are going through the same thing , so , now that I’ve finished , I like it and I always help whenever I can , because I can share what was good for me . (Patient 13)

Relapse/starting over.

Emotional impact . The diagnosis of a relapse is experienced much the same as the initial diagnosis. All of the women report fear, although they also state that they are more familiar with the processes. Other emotions emerge, such as why me, blame, disbelief, etc.

Since they had told me that it wasn’t going to happen again , I believed it , of course , I wanted to believe it and it totally surprised me; I couldn’t stop crying and crying . (Patient 17)

Telling the family again . Patients repeat that telling the family about it again, especially the children and parents, is tough and they try to minimize it in an attempt to protect them emotionally.

On the very same day that I had my mammogram , my mother says that she wants to come a see the kids . We’re in the park , when she arrives , I have to tell her that everything’s fine and when we get home , I tell her everything . My mother’s devastated again and I tell her not to worry , that everything is going to be fine . (Patient 16)

Thinking about whether something could have been done differently . Several women comment that, after their relapse, they think about whether the treatment was enough or there must have been something they could have done to avoid the relapse.

You get furious , because you say , “I wasn’t supposed to get sick , because if , 2 years ago when the first microcalcifications appeared I had had them removed , then I wouldn’t have metastasis , or maybe I would . (Patient 19)

Metastatic breast cancer/time-limited chronic.

Re-interpreting the concept of metastasis . Most of the participants in this stage state that they have had to give new meaning to the word, “metastasis,” since their first perception was directly related to death. In this way, they come to understand that cancer can become chronic, although they now have to take medication and go to the hospital on a regular basis. Nevertheless, they know that their life expectancy may be a few years. The women who are involved in a group point out how hard it is to see their fellow member pass away.

What I now call my “ new normal” consists of lots of visits to the hospital and never going back to work . (Patient18)

They also state that at this stage, they do not identify with the disease generally known socially as “breast cancer”, where there is great emphasis placed on early detection and on their chances of being cured. This causes them to feel more isolated.

These pink ribbon campaigns hurt us because they tend to underscore that everything is going to turn out fine because breast cancer has a very high cure rate; there is huge lack of awareness . (Patient 20)

Physical and emotional discomfort . Most of the women in this stage report side effects from the treatments, although some comment that good quality-of-life can be preserved. On an emotional level, they say that they sometimes feel a certain agony due to not knowing how much longer the treatment will be effective. They live in a state of uncertainty that they try to cope with by focusing on their day-to-day and experience the good times deeply.

When I’m not in pain , I try not to even remember what I have and go out and have fun with my family and live . (Patient 20)

Several women who have children express with regret that they worry about their children enjoying them and remembering them when they were well. They are sad that they won’t be able to grow up in a normal family. Some also comment the impact this diagnosis is having on their partner.

What I don’t want is for them to carry this baggage of having a sick mother . (Patient 18)

A conflict with disability also appears, as many women report their desire to continue working, but feel that they can’t keep up with the pace of work. Additionally, several state that going through the medical board is a strenuous process, given that they look good physically.

It’s hard to deal with , I’m a non-practicing lawyer and I have degrees galore , but I worked the first year and I couldn’t continue . (Patient 21) Every year they call me again for the disability monitoring and they always threaten me . To be honest , the treatment doesn’t make me sick , but I don’t know how long it’s going to be like this . (Patient 19)

Social invisibility . The participants say that they do not have any physical signs of being ill, that they look fine, although they know and feel that inside, they are not well. They say that it is sometimes hard to manage socially, since on occasion, they feel misunderstood and disparaged.

I’m much sicker now , but people think or want to think that I’m fine . When I was doing chemo , it was like wearing a sign that said “cancer . ” (Patient 17)

This study describes the patient journey of women with breast cancer, specifying the different phases with the most relevant aspects of each, as well as the different cross-sectional features they report throughout the entire treatment process.

The results portray breast cancer as a process in which there is a striking feeling of loss of health and self-identity, changes in routines, personal and employment transformation, as well as emotional hardship during and after breast cancer treatment, aspects that are also reported in the literature [ 41 , 42 ]. Earlier studies state that experiencing cancer is highly stressful. It involves a major threat to life or physical integrity, in addition to mental health, interfering with the path, projects, and plans patients have for their life over the short, medium, and, on occasion, long term as well [ 6 ]. Along with reporting adverse physical and psychological impacts, patients also report positive ways in which they have grown psychologically or emotionally from the experience [ 7 , 42 ]. The diagnosis of breast cancer not only impacts the women individually, but also affects their surroundings. As reported in the literature, despite going through a very challenging time, the women struggle to put on a positive face and attempt to conserve the family’s well-being, specifically that of their children [ 7 ]. At the same time, the family is a fundamental source of support and usually provide indispensable support; however, it is not always effective, because family members do not fully understand the stresses involved in living with cancer [ 43 ]. Previous studies also reveal that for some women, their partners are one of their most significant supports; nonetheless, research also suggests that a cancer diagnosis predicts marital breakup more strongly for female survivors than males [ 44 ]. Our results reflect that the women frequently resort to other women in the same situation, possibly because they face significant unmet supportive care needs [ 30 ]. The need for social support may lead patients to seek social support groups consisting of people who are experiencing similar health crises, because such groups allow them to interact with those who best understand their suffering [ 43 ]. Another aspect that appears across the board is the relationship the participants have with the medical team. In this study, we have noted their trust in the medical team and acceptance of the treatments proposed without going into the clinical data of the disease and without needing to know the benefit provided by the treatment. Cancer patients are confronted with a potentially life-threatening [condition], feeling vulnerable, and need to rely heavily on their care providers, expecting the physician to act in their best interests [ 5 ]. Therefore, they need to have a close relationship, as well as comprehensive care [ 30 ]. Patients’ trust in a physician has been associated with a reduction of their fears and anxiety and [increased] satisfaction and adherence to treatment [ 5 , 30 ]. We believe that it would be important to provide patients with accurate information, so as to avoid misunderstandings (such as cancer being synonymous with death, regardless of stage) as several participants in this study have reported, which can lead them to believe that the risk of relapse with and without chemotherapy is much greater than the oncologists estimate [ 45 ]. We believe that in future studies that it would be worthwhile to examine the peculiarities of each kind of patient information with the aim of determining how to break it up and make it both comprehensible and tolerable to promote patients’ well-being.

A breast cancer diagnosis is generally unexpected and practically all patients suffer psychological distress, such as feelings of uncertainty, disbelief, hopelessness, vulnerability, anger, fear, anxiety, and sadness [ 46 , 47 ]. The literature has reported that many women experience peritraumatic distress or dissociation during the medical conversation in which they are given their diagnosis of cancer [ 48 ], which might account for the reactions of the respondents. Given that, when they receive their diagnosis, additional information is generally given to them, such as clinical aspects and preferred treatments. Repeating this information at subsequent appointments could contribute to improving communication with patient, since several participants stated that they found it hard to pay attention to the physician, given the emotional impact. Additionally, breast cancer patients tend to be diagnosed when they are relatively young, and often when they are in the middle furthering their career or raising children [ 12 ]. In spite of everything, the women try to put on as brave a face as they can and focus on maintaining their children’s well-being [ 7 ]. Telling children about their diagnosis is reportedly one of the biggest challenges; parents are usually unsure of how to tell them, because at the same time that they want it to be open and honest and cover their children’s developmental needs, they also want to protect them children [ 49 ].

Once diagnosed, breast cancer patients go through different treatments. The most salient experiences of these phases pertain to the impact of side effects on physical quality-of-life and psychological well-being, which is consistent with the literature [ 11 ]. Moreover, cancer therapy entails physical changes that affect their feminine identity, fertility, self-esteem, sexual functioning, and makes them more vulnerable [ 10 , 50 ]. Women described their inner self as being on an emotional rollercoaster with highs and lows throughout the various phases of treatment [ 7 ]. Given treatment side effects and sequelae, these women are more likely to experience physical symptoms and psychological disorders than patients with other kinds of tumors [ 51 ]. The side effects involve an acute sense of loss of health and quality-of-life, as well as identity and femininity. It would be interesting for future research to explore the therapies used in grief counseling with cancer patients, as understanding and exploring this perspective could comprise an additional clinical aid.

Once the women have completed their treatments, they gradually get back to normal and many contemplate returning to work. However, in line with our results, the literature reveals that even though they want to normalize their lives, female breast cancer survivors feel that they will never return to their baseline status [ 7 ]. A significant number of patients experience difficulties in physical, cognitive, and emotional functioning after their treatment, such as symptoms like lymphedema, fatigue, pain, sleep disorders, cancer-related cognitive impairment, emotional stress, symptoms of depression and anxiety, problems with relationships, reduced sexual identity, fertility problems, and fear of cancer relapse [ 13 , 14 ]. Furthermore, patients with hormone therapy suffer hot flashes, sweats, joint pain, weight gain, decreased libido, and low energy [ 52 ]. A sizeable number of these women also experience changes in employment status which can happen even 5–10 years following diagnosis [ 15 ]. Given that all these changes alter the structure of the woman’s everyday life, personalized care and treatment plans in cancer survivors are highlighted in the literature with extended specialized support being proposed that enables them to make a better psychosocially adjusted transition from treatment to follow-up [ 53 ] and advocating for the patient’s participation in all decisions that affect her during this period [ 54 ]. Further research is needed concerning how to structure the follow-up and support offered to these women during this stage so as to meet their needs and help them adjust to their new reality with the chronic sequelae caused by cancer and its treatment. On the other hand, the personal transformation of the initial stages of the journey are best seen during this phase. The literature shows that women who have had breast cancer report changes in their philosophy of life, such as embarking on a new life path, changing their priorities in life, as well as valuing life in general [ 42 ]. Most of the participants in our study place special emphasis on appreciating life, enjoying it more, and living each day to the fullest. Cancer survivors report being aware of how precarious life is, while also feeling the joy of being alive [ 55 ]. Similarly, they have been found to be more resilient and better able to repair their mood than healthy women [ 56 ].

About 5% of all patients with breast cancer are diagnosed when the disease is metastatic, whereas some 30% have suffered a relapse of an early breast cancer [ 17 ]. We saw that some women suffering a relapse after initial treatment with curative intent tend to wonder if the treatment was sufficient or if they should have done something more to prevent the relapse. Metastatic breast cancer is uncurable, which is why these women’s main psychosocial challenges are not the same as those who are diagnosed in early stages [ 18 ]. Faced with incurability, the women react with shock and fear of imminent death, but this anxiety diminishes once they begin treatment and learn that there are more treatment options [ 17 ]. During this phase, the interviewees reported impaired physical QoL and functioning, being hindered by pain, fatigue, or menopausal symptoms. Emotionally, they report suffering bouts of depression and anxiety, as well as fear because of the spread of their cancer. As for their relational QoL, their children’s welfare is their number one concern, especially for mothers of young children [ 17 , 57 ]. What’s more, these women felt isolated from society in general and, more specifically, from the non-advanced breast cancer community, inasmuch as they feel that nobody understands what they are going through [ 18 ]. A psychosocial approach is especially important in this phase to help these women to continuously adapt to the changes of their individual clinical situation and to the progression of the disease, thereby improving their coping.

Clinical implications

Having first-person information enables us to comprehend in detail the experiences of breast cancer patients, their situation, and emotional state, which favors holistic cancer care for health professionals.

Healthcare professionals should prepare women for a changed life situation, as well as to face prolonged, multimodal treatment (surgery, chemotherapy, hormone therapy, radiotherapy), and to confront physical and psychological sequelae, as well as the fear surrounding an uncertain prognosis. It is important to help them manage their expectations and fears and, to identify and address the issues and concerns that arise at different time points during treatment. The information and support offered should be adjusted to each woman’s individual needs, her life situation, her coping style, and the time and stage of their cancer. This more empathic, understanding outlook can also contribute to improving the physician-patient rapport, promoting communication, understanding, and shared decision-making.

Finally, a comprehensive understanding of the women’s psychosocial support endorses their belonging to groups of women with breast cancer, in which there is a relationship among equals. Further research is needed to specify the type needed so as to decrease both the impact of the death of women in the group, as well as the vast amount of information that they may end up obtaining, without needing it or requesting it.

Limitations

This study was performed with Spanish participants, which is why certain aspects cannot reflect the experiences of breast cancer patients from other countries, given the particularities of both the Spanish healthcare system and Spanish culture. Likewise, the data attained were specific to women with breast cancer, which can scarcely be extrapolated to individuals with other cancers. Moreover, the findings do not reflect men’s experiences with breast cancer and research with this group would enrich the field further. In addition, the age of our participants ranged from 34 to 61 years; hence the results should be interpreted for a middle-aged population and do not reflect the experiences of women diagnosed at very early or very old ages. Finally, we believe that there may be a bias regarding the women who agree to participate, as this group has probably accepted their condition more, as well as having worked on it more.

Despite these limitations, we hope that our findings can contribute to better understanding the experiences of women with breast cancer.

Acknowledgments

The authors are grateful to the investigators of the Neoetic study and the Bioetic Group of the Spanish Society of Medical Oncology (SEOM) for their contribution to this study. We would like to thank all the women who generously shared their experiences with us, the support of HealthyOnco ( www.healthyonco.com ), and Priscilla Chase Duran for editing and translating the manuscript.

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Gene variants foretell the biology of future breast cancers in Stanford Medicine study

In a finding that vastly expands the understanding of tumor evolution, researchers discover genetic biomarkers that can predict the breast cancer subtype a patient is likely to develop.

May 30, 2024 - By Krista Conger

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Stanford Medicine researchers found that inherited gene sequences can predict what type of breast cancer a patient is likely to develop, along with how aggressive that cancer may be.   Emily Moskal

A Stanford Medicine study of thousands of breast cancers has found that the gene sequences we inherit at conception are powerful predictors of the breast cancer type we might develop decades later and how deadly it might be.

The study challenges the dogma that most cancers arise as the result of random mutations that accumulate during our lifetimes. Instead, it points to the active involvement of gene sequences we inherit from our parents — what’s known as your germline genome — in determining whether cells bearing potential cancer-causing mutations are recognized and eliminated by the immune system or skitter under the radar to become nascent cancers. 

“Apart from a few highly penetrant genes that confer significant cancer risk, the role of hereditary factors remains poorly understood, and most malignancies are assumed to result from random errors during cell division or bad luck,” said Christina Curtis , PhD, the RZ Cao Professor of Medicine and a professor of genetics and of biomedical data science. “This would imply that tumor initiation is random, but that is not what we observe. Rather, we find that the path to tumor development is constrained by hereditary factors and immunity. This new result unearths a new class of biomarkers to forecast tumor progression and an entirely new way of understanding breast cancer origins.”

Curtis is the senior author of the study, which will be published May 31 in Science . Postdoctoral scholar Kathleen Houlahan , PhD, is the lead author of the research.

“Back in 2015, we had posited that some tumors are ‘born to be bad’ — meaning that their malignant and even metastatic potential is determined early in the disease course,” Curtis said. “We and others have since corroborated this finding across multiple tumors, but these findings cast a whole new light on just how early this happens.”

A new take on cancer’s origin

The study, which gives a nuanced and powerful new understanding of the interplay between newly arisen cancer cells and the immune system, is likely to help researchers and clinicians better predict and combat breast tumors.

Currently, only a few high-profile cancer-associated mutations in genes are regularly used to predict cancers, but these account for a small minority of cases. Those include BRCA1 and BRCA2, which occur in about one of every 500 women and confer an increased risk of breast or ovarian cancer, and rarer mutations in a gene called TP53 that causes a disease called Li Fraumeni syndrome, which predisposes to childhood and adult-onset tumors.

Christina Curtis

Christina Curtis

The findings suggest there are tens or hundreds of additional gene variants — identifiable in healthy people — that through interactions with the immune system pull the strings that determine why some people remain cancer-free throughout their lives.

“Our findings not only explain which subtype of breast cancer an individual is likely to develop,” Houlahan said, “but they also hint at how aggressive and prone to metastasizing that subtype will be. Beyond that, we speculate that these inherited variants may influence a person’s risk of developing breast cancer. However, future studies will be needed to examine this.”  

The genes we inherit from our parents are known as our germline genome. They’re mirrors of our parents’ genetic makeup, and they can vary among people in small ways that give some of us blue eyes, brown hair or type O blood. Some inherited genes include mutations that confer increased cancer risk from the get-go, such as BRCA1, BRCA2 and TP53.

In contrast, most cancer-associated genes are part of what’s known as our somatic genome. As we live our lives, our cells divide and die in the tens of millions. Each time the DNA in a cell is copied, mistakes happen and mutations can accumulate. DNA in tumors is often compared with the germline genomes in blood or normal tissues in an individual to pinpoint which changes likely led to the cell’s cancerous transformation.

Classifying breast cancers

In 2012, Curtis began a deep dive — assisted by machine learning — into the types of somatic mutations that occur in thousands of breast cancers. She was eventually able to categorize the disease into 11 subtypes with varying prognoses and risk of recurrence, finding that four of the 11 groups were significantly more likely to recur even 10 or 20 years after diagnosis — critical information for clinicians making treatment decisions and discussing long-term prognoses with their patients.

Prior studies had shown that people with inherited BRCA1 mutations tend to develop a subtype of breast cancer known as triple negative breast cancer. This correlation implies some behind-the-scenes shenanigans by the germline genome that affects what subtype of breast cancer someone might develop.

“We wanted to understand how inherited DNA might sculpt how a tumor evolves,” Houlahan said. To do so, they took a close look at the immune system.

It’s a quirk of biology that even healthy cells routinely decorate their outer membranes with small chunks of the proteins they have bobbing in their cytoplasm — an outward display that reflects their inner style.

Kathleen Houlahan

Kathleen Houlahan

The foundations for this display are what’s known as HLA proteins, and they are highly variable among individuals. Like fashion police, immune cells called T cells prowl the body looking for any suspicious or overly flashy bling (called epitopes) that might signal something is amiss inside the cell. A cell infected with a virus will display bits of viral proteins; a sick or cancerous cell will adorn itself with abnormal proteins. These faux pas trigger the T cells to destroy the offenders.

Houlahan and Curtis decided to focus on oncogenes, normal genes that, when mutated, can free a cell from regulatory pathways meant to keep it on the straight and narrow. Often, these mutations take the form of multiple copies of the normal gene, arranged nose to tail along the DNA — the result of a kind of genomic stutter called amplification. Amplifications in specific oncogenes drive different cancer pathways and were used to differentiate one breast cancer subtype from another in Curtis’ original studies.

The importance of bling

The researchers wondered whether highly recognizable epitopes would be more likely to attract T cells’ attention than other, more modest displays (think golf-ball-sized, dangly turquoise earrings versus a simple silver stud). If so, a cell that had inherited a flashy version of an oncogene might be less able to pull off its amplification without alerting the immune system than a cell with a more modest version of the same gene. (One pair of overly gaudy turquoise earrings can be excused; five pairs might cause a patrolling fashionista T cell to switch from tutting to terminating.)

The researchers studied nearly 6,000 breast tumors spanning various stages of disease to learn whether the subtype of each tumor correlated with the patients’ germline oncogene sequences. They found that people who had inherited an oncogene with a high germline epitope burden (read: lots of bling) — and an HLA type that can display that epitope prominently — were significantly less likely to develop breast cancer subtypes in which that oncogene is amplified.

There was a surprise, though. The researchers found that cancers with a large germline epitope burden that manage to escape the roving immune cells early in their development tended to be more aggressive and have a poorer prognosis than their more subdued peers.

“At the early, pre-invasive stage, a high germline epitope burden is protective against cancer,” Houlahan said. “But once it’s been forced to wrestle with the immune system and come up with mechanisms to overcome it, tumors with high germline epitope burden are more aggressive and prone to metastasis. The pattern flips during tumor progression.”

“Basically, there is a tug of war between tumor and immune cells,” Curtis said. “In the preinvasive setting, the nascent tumor may initially be more susceptible to immune surveillance and destruction. Indeed, many tumors are likely eliminated in this manner and go unnoticed. However, the immune system does not always win. Some tumor cells may not be eliminated and those that persist develop ways to evade immune recognition and destruction. Our findings shed light on this opaque process and may inform the optimal timing of therapeutic intervention, as well as how to make an immunologically cold tumor become hot, rendering it more sensitive to therapy.”

The researchers envision a future when the germline genome is used to further stratify the 11 breast cancer subtypes identified by Curtis to guide treatment decisions and improve prognoses and monitoring for recurrence. The study’s findings may also give additional clues in the hunt for personalized cancer immunotherapies and may enable clinicians to one day predict a healthy person’s risk of developing an invasive breast cancer from a simple blood sample.

“We started with a bold hypothesis,” Curtis said. “The field had not thought about tumor origins and evolution in this way. We’re examining other cancers through this new lens of hereditary and acquired factors and tumor-immune co-evolution.”

The study was funded by the National Institutes of Health (grants DP1-CA238296 and U54CA261719), the Canadian Institutes of Health Research and the Chan Zuckerberg Biohub.

Krista Conger

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

Hope amid crisis

Psychiatry’s new frontiers

Stanford Medicine magazine: Mental health

Most younger women who want kids after breast cancer are successful, research data shows

About two-thirds of the women in the study had a baby after diagnosis.

Among younger women with breast cancer, it may be possible for many to have a baby after their diagnosis thanks to advances in breast cancer care, new research suggests.

In a study of about 200 women ages 40 and younger with non-metastatic breast cancer who wanted children, roughly three-quarters were able to become pregnant after diagnosis, and about two-thirds had a baby.

The research will be presented on Monday, June 3, at the 2024 ASCO Annual Conference, a major medical conference of the American Society of Clinical Oncology. However, it has not yet been peer-reviewed or published as a full manuscript in a journal.

PHOTO: Among younger women with breast cancer, new research suggests it may be possible for many to have a baby after their diagnosis, thanks to advances in breast cancer care.

MORE: Major disparities exist in women of color's access to breast cancer care, report finds

Doctors say this may give hope to the growing number of younger people being diagnosed with breast cancer who want to preserve their fertility.

"This is indeed great news for young breast cancer survivors," Dr. Julie R. Gralow, Chief Medical Officer of ASCO and oncologist who specializes in breast cancer, told ABC News. "Achieving a pregnancy after breast cancer diagnosis is both possible and safe."

For women diagnosed at earlier ages, fertility may be of great concern and importance, but experts point out that in this study, only 16% of women said they desired a baby after their diagnosis.

"I think this may represent the overall reluctance of young women with this diagnosis interrupting their lives at such a young age to pursue pregnancy," Dr. Julia Foldi, assistant professor of medicine in hematology/oncology, University of Pittsburgh School of Medicine, told ABC News.

PHOTO: Among younger women with breast cancer, new research suggests it may be possible for many to have a baby after their diagnosis, thanks to advances in breast cancer care.

In the study, women with more financial security were more likely to become pregnant, and fertility preservation, such as egg freezing, nearly tripled the odds of having a baby. The older the patient, the less likelihood of having a baby or getting pregnant.

"While we can't impact the age at diagnosis, we can make sure that all young women diagnosed with breast cancer receive information prior to beginning treatment about options to increase the chance of a future pregnancy, and also have access to those options," Gralow said.

Doctors hope this research helps counsel women who desire pregnancy after their breast cancer diagnosis and highlights the importance of having access to fertility preservation services, which can be costly.

"Timely access to fertility preservation can be very challenging due to lack of available resources and infrastructure, financial barriers, and much more," Dr. Kimia Sorouri, research fellow, Dana-Farber Cancer Institute, Boston, Massachusetts, and one of the study authors told ABC News.

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"Ensuring that women have the resources necessary to enable them to benefit from this technology, including insurance coverage for fertility preservation, will go a long way towards ensuring access to care for those women who have yet to complete their reproductive plan," Dr. Sigal Klipstein, InVia Fertility Specialists in Chicago and former chair of the ACOG Committee on Ethics, told ABC News.

PHOTO: Among younger women with breast cancer, new research suggests it may be possible for many to have a baby after their diagnosis, thanks to advances in breast cancer care.

MORE: Finalized guidance drops breast cancer screening age to 40 for women with average risk

Researchers also found several factors that were not associated with fertility outcomes in this study, including having a history of infertility, never giving birth before diagnosis, tumor characteristics, cancer treatment, race, and ethnicity.

"It is particularly impressive data because almost 70% of the women in this study had received chemotherapy, which can reduce fertility," Gralow said.

In this study, the typical age at the time of breast cancer diagnosis was 32 years old, and the average time to pregnancy was 4 years after diagnosis. Most of the women in this study were non-Hispanic white and had their breast cancer diagnosed in earlier stages of the disease.

"This should encourage folks to get their screening done and know that if they are diagnosed earlier on, that's less likely to impact their future fertility goals," Dr. Elizabeth Langen, associate clinical professor of obstetrics and gynecology, University of Michigan Health System, told ABC News.

In guidance by the U.S. Preventive Services Task Force, women with average risk are now recommended to start breast cancer screening at age 40.

This finalized guidance, in part, reflects a worrying trend of more women being diagnosed with breast cancer at a younger age.

"While this study provides great hope for women with a diagnosis of breast cancer, it is important to be cognizant of the fact that not all women will have success," Klipstein said. "Expeditious counseling, availability of and access to fertility preservation options are the elements that often make the difference between having or not having the family that women desire."

Dr. Jade A Cobern, MD, MPH, a licensed and practicing physician board certified in pediatrics and preventive medicine, is a member of the ABC News Medical Unit.

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