Mastectomy or Breast-Conserving Therapy for BRCA1/2 Variant Carriers | Breast Cancer | JAMA Network Open | JAMA Network
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Invited Commentary
April 23, 2021

Mastectomy or Breast-Conserving Therapy for BRCA1/2 Variant Carriers

Author Affiliations
  • 1Department of Surgery, Wake Forest Baptist Health, Winston-Salem, North Carolina
JAMA Netw Open. 2021;4(4):e216391. doi:10.1001/jamanetworkopen.2021.6391

Wan et al1 have retrospectively reviewed 8396 patients with stage I or II breast cancer, 491 with a known BRCA1 (OMIM 113705) or BRCA2 (OMIM 600185) variant, and compared the survival rate among patients undergoing breast-conserving therapy (BCT) with the survival rate among patients undergoing mastectomy, for variant carriers vs noncarriers. From NSABP B-06, EORTC 10801, and other studies, we know that BCT with radiotherapy offers overall survival similar to mastectomy.2,3 Recently, studies have shown that BCT with radiotherapy may be associated with improved survival compared with mastectomy.4 What about survival after BCT among women with a BRCA1/2 germline variant? These women are at increased risk of developing a second primary breast cancer in the same or contralateral breast.5 Wan et al1 found that, after 7.5 years of follow-up, BRCA1/2 variant carriers treated with BCT had no better survival than those treated with mastectomy (overall survival: hazard ratio [HR] for BRCA1, 0.61 [95% CI, 0.18-2.12]; P = .44; HR for BRCA2, 0.72 [95% CI, 0.26-1.96]; P = .52) or mastectomy (overall survival: HR for BRCA1, 0.77 [95% CI, 0.27-2.21]; P = .63; HR for BRCA2, 0.62 [95% CI, 0.22-1.73]; P = .37). They concluded that BRCA1/2 variant carriers treated with BCT have a survival comparable to those treated with mastectomy. To our knowledge, this is one of the largest studies to date on this topic.

The surgical treatment of patients with a genetic germline variant is complicated. In the study by Wan et al,1 conducted in China, patients and their physicians were unaware of their BRCA1/2 variant status. This is not the case in the United States, where most multidisciplinary clinics try to test patients with a suspicious family history of breast and/or ovarian cancer or women who meet National Comprehensive Cancer Network guidelines prior to undergoing surgery. Patients then are armed with the information about the implications that their genetic variant status has on subsequent risk of developing a second cancer in the future. This information can be used by patients who tend to choose bilateral mastectomy.6 However, the information provided by Wan and colleagues1 may help inform patients with BRCA1/2 variants that BCT offers survival comparable to mastectomy.

The other important issue in surgical decision-making for BRCA1/2 carriers is the contralateral breast. Patients with these variants have an increased risk of developing contralateral breast cancer, and mastectomy serves as a strong means to reduce that risk. Wan et al1 found that the rates of contralateral breast cancer were higher among BRCA1/2 carriers than among noncarriers. They concluded that the increased risk of contralateral breast cancer may outweigh the benefits of breast conservation. This factor is at the heart of the conversation with BRCA1/2 variant carriers. If a patient decides to undergo BCT for their cancer, we would still have to closely screen patients, with mammograms alternating with breast magnetic resonance imaging every 6 months to catch cancer at an early stage, whereas if a patient decides to undergo bilateral mastectomy, this intense screening, which can become emotionally and financially draining for patients, is not needed.

This study by Wan et al1 is a large retrospective study examining outcomes and survival among BRCA1/2 carriers addressing surgical approach and survival. The study adds much to our knowledge about treatment regimens for patients. However, surgical choice is a complex decision-making process that the patient and the physician are best to approach in a collaborative way, involving much thought and conversation.

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Article Information

Published: April 23, 2021. doi:10.1001/jamanetworkopen.2021.6391

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Howard-McNatt M. JAMA Network Open.

Corresponding Author: Marissa Howard-McNatt, MD, Department of Surgery, Wake Forest Baptist Health, Winston-Salem, NC 27157 (

Conflict of Interest Disclosures: None reported.

Wan  Q, Su  L, Ouyang  T,  et al.  Comparison of survival after breast-conserving therapy vs mastectomy among patients with or without the BRCA1/2 variant in a large series of unselected Chinese patients with breast cancer.   JAMA Netw Open. 2021;4(4):e216259. doi:10.1001/jamanetworkopen.2021.6259Google Scholar
Fisher  B, Anderson  S, Bryant  J,  et al.  Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.   N Engl J Med. 2002;347(16):1233-1241. doi:10.1056/NEJMoa022152 PubMedGoogle ScholarCrossref
Litière  S, Werutsky  G, Fentiman  IS,  et al.  Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial.   Lancet Oncol. 2012;13(4):412-419. doi:10.1016/S1470-2045(12)70042-6 PubMedGoogle ScholarCrossref
Agarwal  S, Pappas  L, Neumayer  L, Kokeny  K, Agarwal  J.  Effect of breast conservation therapy vs mastectomy on disease-specific survival for early-stage breast cancer.   JAMA Surg. 2014;149(3):267-274. doi:10.1001/jamasurg.2013.3049 PubMedGoogle ScholarCrossref
Mavaddat  N, Peock  S, Frost  D,  et al; EMBRACE.  Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.   J Natl Cancer Inst. 2013;105(11):812-822. doi:10.1093/jnci/djt095PubMedGoogle ScholarCrossref
Yadav  S, Reeves  A, Campian  S, Sufka  A, Zakalik  D.  Preoperative genetic testing impacts surgical decision making in BRCA mutation carriers with breast cancer: a retrospective cohort analysis.   Hered Cancer Clin Pract. 2017;15:11. doi:10.1186/s13053-017-0071-zPubMedGoogle ScholarCrossref
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