Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer
Abstract
Purpose: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.
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Four studies including selected patients and accounting for competing risks reported higher 10-year contralateral breast cancer risk estimates (21%-27%), similar to the risk observed in this study for mutation carriers with a family history of breast cancer (25%).
“Four studies including”
From Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in <i>BRCA1/2</i> Mutation Carriers (2016) · cites this paper as [24]
The recurrence rate in BRCA1/BRCA2 carriers is not increased in this population of patients.
“We and other authors demonstrated that the recurrence rate in BRCA1/BRCA2 carriers is not increased in this population of patients [28-32].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [30]
All studies of BRCA1 and/or BRCA2 mutation carriers so far have reported an increased incidence of contralateral breast cancer.
“All studies of BRCA1 and/or BRCA2 mutation carriers so far have reported an increased incidence of contralateral breast cancer [9, 15, 28-30, 37, 38, 40].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [30]
The safety of BCT in BRCA mutation carriers is a matter of debate.
“However, its safety in BRCA mutation carriers is a matter of debate, and several studies have compared ipsilateral tumour recurrence after breast-conserving treatment (BCT) in BRCA1 and BRCA2 mutation carriers and patients with sporadic cancers [9, 28-32, 37-41].”
From Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature (2010) · cites this paper as [30]
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- Authors
- Pierce, L. J., Levin, A. M., Rebbeck, T. R., Ben-David, M. A., Friedman, E., Solin, L. J., Harris, E. E., Gaffney, D. K., Haffty, B. G., Dawson, L. A., Narod, S. A., Olivotto, I. A., Eisen, A., Whelan, T. J., Olopade, O. I., Isaacs, C., Merajver, S. D., Wong, J. S., Garber, J. E., & Weber, B. L.
- Affiliations
- Georgetown University (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2006-06-01
- Volume
- 24
- Issue
- 16
- Pages
- 2437-2443
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2124189233
- Cited by
- 340
- References
- 24
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 8 · 2023: 3 · 2022: 15 · 2021: 17 · 2020: 20 · 2019: 10 · 2018: 7 · 2017: 13 · 2016: 15 · 2015: 17 · 2014: 10 · 2013: 21 · 2012: 27
- FWCI
- 16.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30CA051008, P30 CA51008-12)
- National Center for Research Resources (M01-RR 00064, M01RR000064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Keywords
- BRCA1 mutation carriers, BRCA2 mutation carriers, breast-conserving surgery, adjuvant radiotherapy, contralateral breast cancer, oophorectomy, tamoxifen, high-risk women
- MeSH terms
- Adult, Aged, Breast Neoplasms, Canada, Female, Heterozygote, Humans, Israel, Middle Aged, Mutation, Neoplasm Recurrence, Local, Neoplasm Staging, Ovariectomy, Predictive Value of Tests, Time Factors, United States, Mastectomy, Segmental, Incidence, Multivariate Analysis, Odds Ratio, Case-Control Studies, Treatment Outcome, Radiotherapy, Adjuvant, Genes, BRCA1, Genes, BRCA2
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