Prophylactic nipple-sparing mastectomy and immediate breast reconstruction in Chinese BRCA1/2 carriers: a case series with 45-month follow-up and zero breast cancer incidence

Introduction

BRCA1/2 are highly penetrant breast cancer susceptibility genes. Germline pathogenic variants (PVs) in BRCA1/2 genes confer an increased risk of breast cancer. Numerous studies have shown that the lifetime risk of breast cancer exceeds 60% for BRCA1/2 PV carriers among Caucasian women (1-4). Healthy Chinese women with BRCA1/2 PVs also have a high risk of developing breast cancer, with cumulative risks of 37.9% (BRCA1) and 36.5% (BRCA2) by age 70 years, respectively (5), whereas the corresponding risk of healthy Chinese women without BRCA1/2 PVs was only 3.6%. Bilateral prophylactic mastectomy in BRCA1/2 carriers has been proven to reduce the risk of breast cancer by more than 90% (6-9). Furthermore, some studies have shown that prophylactic mastectomy may be associated with a reduction in both breast cancer mortality and overall mortality in BRCA1/2 carriers (10,11).

The prevalence of prophylactic mastectomy in healthy women with BRCA1/2 PVs varies across countries and populations (12). In the United States, the prophylactic mastectomy rate has been increasing in recent decades, reaching nearly 50% among women with BRCA1/2 PVs (12,13). Currently, nipple-sparing mastectomy (NSM) and immediate breast reconstruction is a favorable option for women who are willing to take this risk-reducing procedure (13), and its safety in BRCA1/2 carriers has been demonstrated in a recent study (14). Up to now, however, this risk-reducing procedure has rarely been reported among healthy Chinese women with BRCA1/2 PVs. This could be attributed to several factors, including limited nationwide availability of BRCA1/2 gene testing, the lack of precise risk estimate, a cultural preference for surveillance rather than prophylactic mastectomy, and limited access to breast reconstruction.

In this study, nine highly selected healthy Chinese women who carried germline BRCA1/2 PVs underwent nipple-sparing prophylactic mastectomy and immediate breast reconstruction. The reasons why the nine carriers underwent prophylactic mastectomy were that most of them had a strong family history of breast cancer and were at high risk of developing breast cancer; additionally, they had a strong desire to undergo prophylactic mastectomy in order to reduce the risk. The Chinese Society of Breast Surgery (CSBrS) also recommended that prophylactic mastectomy could be an option for BRCA1/2 carriers (15). Here, we report the risk-reducing effect after a median follow-up of 45 months in this high-risk group. We present this article in accordance with the AME Case Series reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0113/rc).

Case presentation

Patients

This study included nine healthy Chinese women who carried germline BRCA1/2 PVs (6 BRCA1 carriers and 3 BRCA2 carriers) (Table 1). Three of these patients (cases 1–3) have been reported in our previous study (16). Of these, case 6 and case 7 had previously been diagnosed with triple-negative breast cancer in their left breast; both patients underwent breast-conserving therapy, adjuvant chemotherapy and radiotherapy, and no ipsilateral local recurrence was found before prophylactic mastectomy. The remaining seven were healthy women and none of them had a personal breast cancer history. We discussed with the patients for several rounds regarding the benefits and potential harms of this prophylactic procedure, and they were given sufficient time to make a final decision. Ultimately, all nine women showed a strong willingness to receive NSM and immediate breast reconstruction. Of these nine patients, case 1 was a typical example who carried a BRCA1 PV (c.2899del:p.T967fs) (Table 1). Her aunt, the index case of this family carrying this mutation, suffered from triple-negative breast cancer in the right breast at the age of 39. After receiving eight cycles of neoadjuvant chemotherapy, she underwent a right breast mastectomy. Four years later, her aunt suffered from triple-negative breast cancer in the contralateral (left) breast; after receiving another eight cycles of neoadjuvant chemotherapy, she underwent a left breast mastectomy. Her aunt’s miserable experience had a great impact on her decision-making. Case 1 had an urgent demand to undergo prophylactic mastectomy. No abnormalities were found in the nine carriers; case 5 had scattered calcifications in the left upper outer quadrant, but not reaching Breast Imaging Reporting and Data System (BI-RADS) 4. Physical examination, ultrasound, mammography, and magnetic resonance imaging (MRI) were performed in all of these women before mastectomy, and no imaging abnormalities in the breast were found in the nine women. Therefore, NSM followed by immediate breast reconstruction with silicone implants was performed at Peking University International Hospital from January 2018 to August 2022. Follow-up time was defined as the time from the date of surgery to the date of the last visit. This study was approved by the Research and Ethics Committee of Peking University International Hospital (No. 2020011). All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all patients for participation in this study and for publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

BRCA1/2 variants

Genomic DNA extracted from peripheral blood was tested for the entire coding regions and exon-intron boundaries of BRCA1/2 genes through a multi-gene panel and/or Sanger sequencing. The criteria for classifying a variant as pathogenic are based on ENIGMA BRCA1/2 Gene Variant Classification Criteria (https://enigmaconsortium.org/) and the American College of Medical Genetics and Genomics recommendations. In this study, all patients carried a BRCA1/2 PV, and the PVs were confirmed in two independent genetic agencies and/or institutions.

Baseline characteristics of the study cohort

A total of nine women with BRCA1/2 PVs were enrolled in this study, including six BRCA1 carriers and three BRCA2 carriers (Table 1). The median age when they underwent the surgery was 36 years (range, 34–57 years), and eight out of nine were aged 40 years or younger, except for case 9, who was 57 years old and had suffered from fallopian tube cancer at age 56, and had a strong family history of breast and ovarian cancer. Pedigrees including the first to the third degree relatives were collected in all patients and eight of these women had a family history of breast cancer and/or ovarian cancer in the first- and/or second-degree relatives (Table 1). The age at first breast cancer diagnosis in their families ranged from 33 to 58 years (Table 1). Two cases, cases 6 and 7, were diagnosed with stage I triple-negative breast cancer in their left breast at the ages of 34 and 30 years, respectively. Both patients received breast conserving therapy, and no local or distant recurrence had occurred at the time of undergoing prophylactic mastectomy. The median interval from genetic testing to surgery was 6.6 months (range, 0.2–23.9 months).

Surgical procedure

The operation was performed under general anesthesia with the patient in a supine position. During the surgical procedure, the mastectomy in case 1 and case 2 was done through a circumareolar incision, while the remaining cases were done with a radial incision through the lateral breast. All subcutaneous breast tissue was removed, and the nipple-areolar complex was preserved. The subcutaneous tissue below the nipple was sent for rapid pathological diagnosis, and no malignant findings were identified, therefore the nipple-areolar complex was retained for all the breasts. The skin flap thickness was maintained at approximately 0.5 to 1.0 cm, depending on the individual’s skin thickness. All patients underwent settled silicone breast implant reconstruction on both sides at the time of prophylactic mastectomy. In case 1, the silicone prosthesis was inserted beneath the fascia of the pectoralis major muscle; in cases 2–9, the silicone prosthesis was placed in the posterior space of pectoralis major muscle after dissection of the space between the pectoralis major and minor muscles, as well as the fascia of rectus abdominis, external abdominal oblique muscle, and serratus anterior muscle.

The hospitalization time for the nine women was about two to three weeks. Primary wound healing was achieved in all women, except for case 1, whose wound near the left areola achieved delayed healing in one month after the surgery, and for case 9, whose wound on the right side achieved healing by second intention at four months after the primary operation. No nipple or breast skin necrosis occurred in this series. Case 5 is presented as a representative example, including the mutation and pedigree, surgical procedure, and preoperative and postoperative image (Figure 1A-1D).

Figure 1 The germline pathogenic variant and surgical procedure in Case 5. (A) Case 5 carries a BRCA2 germline pathogenic variant. (B) Family pedigree of case 5, the arrow indicates the index case who underwent prophylactic surgery. (C) Surgical procedure and breast tissue removal during the surgery in case 5. (D) Comparison of breast images before and after the surgery in case 5.

Pathological diagnosis after prophylactic mastectomy

All breast samples (a total of 18 samples) were carefully examined by pathological assessment. Ductal carcinoma in situ was found in two breast samples, one in the right breast of case 1, and another in the left breast of case 5. In case 1, a high grade ductal carcinoma in situ was found in the right breast, with the tumor size of 1 mm limited to one duct. In case 5, two independent lesions of moderate-high grade ductal carcinoma in situ were found in the upper outer quadrant and lower inner quadrant of the left breast, with the tumor size of 3 and 7 mm, respectively (Table 1). Neither invasive carcinoma nor ductal carcinoma in situ was found in the remaining breast samples (Table 1).

Post-operation follow-up

The nine women were followed every 6 months to receive routine breast imaging examinations after the operation. After a median follow-up of 45.0 months (range, 4.0–68.9 months), no breast cancer or other malignancy was observed in the nine patients. All patients reported high aesthetic satisfaction with the surgical outcome and breast symmetry, and their anxiety regarding future breast cancer risk was dramatically reduced. However, the aesthetic satisfaction outcomes were not assessed using standardized tools such as BREAST-Q.

Discussion

To our knowledge, this is the first report of healthy Chinese women with BRCA1/2 germline PVs who underwent prophylactic NSM and immediate breast reconstruction. All nine women reported high aesthetic satisfaction with the surgical outcome and breast symmetry, and no breast cancer occurred in this cohort after a median follow-up of 45 months. In addition, anxiety about developing breast cancer dramatically decreased, and no negative impact on quality of life was found in these women. Our study indicated that prophylactic NSM is feasible for highly selected healthy Chinese women with BRCA1/2 PVs.

The culture and tradition of Chinese women are distinguished from those of Caucasian women. We recently conducted a survey study to explore Chinese healthy women’s preferences for potential intervention approaches, and found that more than 50% of women preferred early detection, and only approximately 25% of women intended to undergo prophylactic mastectomy (17). The magnitude of prophylactic mastectomy in Caucasian women with BRCA1/2 PVs is about 50% (18). Therefore, when Chinese women with BRCA1/2 PVs contemplate prophylactic mastectomy, they usually take a longer time to make a final decision. Indeed, such a decision is not rushed; physicians and patients should discuss prophylactic mastectomy through several rounds of consultation, including the benefits, potential harms, and limitations of the approach. In this cohort, patients took 0.2 months to nearly 2 years to make the final decision; in addition, some potential candidates ultimately opted for early detection (surveillance) instead of prophylactic mastectomy.

Regarding the nine women who finally preferred prophylactic mastectomy, several factors may have influenced their final decision. First, eight of the nine had a family history of breast and/or ovarian or other cancers. A recent study (4) suggested that BRCA1/2 carriers with family history of breast cancer have a two-fold higher risk of breast cancer than those without a family history. In addition, the miserable experiences of affected family members suffering from cancer had a considerable effect on carriers making a final decision. Second, all the patients were married and had given birth, and the support from the family members, especially from husbands, was extremely important. Third, the biological differences between BRCA1 and BRCA2 are also relevant. Although BRCA2 PVs are more common than BRCA1 PVs in Chinese women, in this cohort, six out of nine were BRCA1 carriers. This was largely because BRCA1 carriers are more likely to develop triple-negative breast cancer. Indeed, two patients with BRCA1 PVs (case 6 and 7) had previously developed triple-negative breast cancer and received adjuvant chemotherapy and radiotherapy after breast-conserving therapy. Their prior experience with this breast cancer subtype, together with fear of developing a similar cancer in the affected or contralateral breast, was likely an important reason for choosing prophylactic mastectomy.

In this cohort, we performed nipple-sparing prophylactic mastectomy and immediate implant reconstruction for all nine BRCA1/2 carriers. All the patients had a good cosmetic effect due to retention of the nipple, and no breast cancer occurred during a relatively short follow-up (median 45 months). Recently, NSM and immediate breast reconstruction have been commonly used in BRCA1/2 carriers. This approach is safe in BRCA1/2 carriers, with less than 1% of breast cancer incidence in a relatively long-term studies (median follow-up, 6.8-year) (19), reaffirming prior reports of low recurrence risk (20). However, the survival benefit of prophylactic mastectomy remains uncertain. Recent prospective data suggest that although risk-reducing mastectomy dramatically reduces breast cancer incidence, it may not significantly improve breast cancer-specific or overall survival compared with enhanced surveillance (21). Therefore, decisions regarding prophylactic mastectomy should incorporate not only cancer prevention, but also psychological burden, body image, and potential surgical risk.

Prophylactic mastectomy in BRCA1/2 carriers is recommended at age 25 years and thereafter (22). In our cohort, all the women were over 32 years when they underwent prophylactic mastectomy, which might allow women to give birth and breastfeed.

Among the nine women, two had ductal carcinoma in situ in the pathologic diagnosis, which was not found in the breast image examination before the surgery. Previous studies showed that the rates of occult cancer for prophylactic mastectomy ranged from 4.8% to 14.9% in women with a hereditary predisposition for breast cancer (23-25). Although the proportion in our small series appears relatively high, it should be interpreted cautiously because of the limited sample size. Importantly, the discordance between preoperative imaging and final pathology in these two cases provides clinically relevant insight: even multimodal imaging, including MRI, cannot completely exclude very small lesions in high-risk BRCA1/2 carriers. These findings underscore the importance of careful preoperative imaging detection and meticulous pathological assessment of prophylactic mastectomy specimens. When patients have an invasive breast tumor, further surgical management and treatment may be required, such as axillary lymph node biopsy or adjuvant therapy, depending on the clinical stage and tumor type. In this study, ductal carcinoma in situ in case 1 and case 5 did not need further treatment.

Although no breast cancer events occurred during the current median follow-up of 45 months, this should be considered an intermediate-term observation, and longer follow-up—ideally extending to 10 years—is required to more definitively assess the long-term preventive efficacy and oncologic safety of prophylactic NSM in BRCA1/2 carriers.

In clinical practice, prophylactic NSM should be carefully performed in highly selected Chinese women with BRCA1/2 PVs. For those who would like to undergo prophylactic mastectomy, BRCA1/2 PVs should be confirmed in two independent agencies and should be consistent with the index case of this family. In addition, the potential BRCA1/2 carrier candidates should consider the following factors: family history of breast cancer, support from family members, full understanding of the benefits and limitations of the surgery, and a strong willingness to undergo this procedure. Finally, physicians should allow patients ample time to make a final decision through repeated consultation and counseling.

Conclusions

Our study suggests that prophylactic NSM and immediate breast reconstruction may be a viable option for highly selected healthy Chinese women with BRCA1/2 PVs. Adequate genetic counseling, careful patient selection, multidisciplinary discussion, and sufficient time for informed decision-making are essential before this preventive procedure is undertaken.

Acknowledgments

We thank all individuals who participated in our study.

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0113/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0113/prf

Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 92359201, No. 82272932).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-1-0113/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Research and Ethics Committee of Peking University International Hospital (No. 2020011). All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all patients for participation in this study and for publication of this case series and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Ford D, Easton DF, Bishop DT, et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 1994;343:692-5.
2. King MC, Marks JH, Mandell JB, et al. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003;302:643-6. [Crossref] [PubMed]
3. Mavaddat N, Peock S, Frost D, et al. Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 2013;105:812-22. [Crossref] [PubMed]
4. Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA 2017;317:2402-16. [Crossref] [PubMed]
5. Yao L, Sun J, Zhang J, et al. Breast cancer risk in Chinese women with BRCA1 or BRCA2 mutations. Breast Cancer Res Treat 2016;156:441-5. [Crossref] [PubMed]
6. Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001;93:1633-7. [Crossref] [PubMed]
7. Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2004;22:1055-62. [Crossref] [PubMed]
8. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967-75. [Crossref] [PubMed]
9. Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:159-64. [Crossref] [PubMed]
10. Heemskerk-Gerritsen BAM, Jager A, Koppert LB, et al. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 2019;177:723-33. [Crossref] [PubMed]
11. Metcalfe K, Huzarski T, Gronwald J, et al. Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis. Br J Cancer 2024;130:269-74. [Crossref] [PubMed]
12. Metcalfe K, Eisen A, Senter L, et al. International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer 2019;121:15-21. [Crossref] [PubMed]
13. Nagura N, Hayashi N, Takei J, et al. Breast reconstruction after risk-reducing mastectomy in BRCA mutation carriers. Breast Cancer 2020;27:70-6. [Crossref] [PubMed]
14. Blondeaux E, Sonnenblick A, Agostinetto E, et al. Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study. Lancet Oncol 2025;26:759-70. [Crossref] [PubMed]
15. Xie F, Wang S. Clinical practice guideline of BRCA1/2 testing for patients with breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guideline 2021. Chin Med J (Engl) 2021;134:1516-8. [Crossref] [PubMed]
16. Zhang D, Fu F, Xie L, et al. Clinical practice of prophylactic nipple- sparing mastectomy and immediate reconstruction in Chinese healthy women with BRCA1/BRCA2 germline mutation. Chin J Clin Oncol 2020;47:30-4.
17. Yu X, Kou F, Xie Y. Attitude towards genetic testing for breast cancer susceptibility genes and choice of prevention strategies in Chinese women with or without breast cancer. Cancer Biol Med 2025;22:28-32. [Crossref] [PubMed]
18. Meijers-Heijboer EJ, Verhoog LC, Brekelmans CT, et al. Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation. Lancet 2000;355:2015-20. [Crossref] [PubMed]
19. Amburn T, Parvin-Nejad FP, Sevilimedu V, et al. Oncologic safety of prophylactic nipple-sparing mastectomy: Outcomes of 1,255 cases exceeding a 6-year median follow-up. Breast Cancer Res Treat 2026;215:72. [Crossref] [PubMed]
20. Jakub JW, Peled AW, Gray RJ, et al. Oncologic Safety of Prophylactic Nipple-Sparing Mastectomy in a Population With BRCA Mutations: A Multi-institutional Study. JAMA Surg 2018;153:123-9. [Crossref] [PubMed]
21. Gandhi A, Howell SJ, Harkness EF, et al. Survival Outcomes With or Without Risk-Reducing Mastectomy in BRCA1 and BRCA2 Pathogenic Variant Carriers. J Clin Oncol 2026;44:874-82. [Crossref] [PubMed]
22. Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol 2010;28:222-31. [Crossref] [PubMed]
23. Burger A, Thurtle D, Owen S, et al. Sentinel lymph node biopsy for risk-reducing mastectomy. Breast J 2013;19:529-32. [Crossref] [PubMed]
24. Hoogerbrugge N, Bult P, de Widt-Levert LM, et al. High prevalence of premalignant lesions in prophylactically removed breasts from women at hereditary risk for breast cancer. J Clin Oncol 2003;21:41-5. [Crossref] [PubMed]
25. Boughey JC, Khakpour N, Meric-Bernstam F, et al. Selective use of sentinel lymph node surgery during prophylactic mastectomy. Cancer 2006;107:1440-7. [Crossref] [PubMed]