Bilateral Mastectomy and Breast Cancer Mortality

Vasily Giannakeas; David W. Lim; Steven A. Narod

doi:10.1001/jamaoncol.2024.2212

Original Investigation

July 25, 2024

Bilateral Mastectomy and Breast Cancer Mortality

Vasily听Giannakeas,听PhD, MPH^1,2,3; David W.听Lim,听MDCM, MEd, PhD^1,4,5,6; Steven A.听Narod,听MD^1,3,6

Author Affiliations Article Information

¹Women鈥檚 College Research Institute, Women鈥檚 College Hospital, Toronto, Ontario, Canada
²Women鈥檚 Age Lab, Women鈥檚 College Hospital, Toronto, Ontario, Canada
³Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
⁴Department of Surgery, Women鈥檚 College Hospital, Toronto, Ontario, Canada
⁵Department of Surgery, Division of General Surgery, University of Toronto, Toronto, Ontario, Canada
⁶Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

JAMA Oncol. 2024;10(9):1228-1236. doi:10.1001/jamaoncol.2024.2212

Full Text

Key Points

Question听 Does bilateral mastectomy for treatment of unilateral breast cancer reduce the 20-year risk of breast cancer mortality?

Findings听 This cohort study including 661鈥�270 women with unilateral breast cancer who were closely matched by treatment type (lumpectomy, unilateral mastectomy, or bilateral mastectomy) and followed up for 20 years found that bilateral mastectomy was associated with a statistically significant reduction of contralateral breast cancer risk but not breast cancer mortality.

Meaning听 These findings indicating that contralateral mastectomy for unilateral breast cancer is an effective means of cancer prevention but does not reduce the risk of dying of breast cancer call into question the metastatic potential of a de novo contralateral cancer.

Abstract

Importance听 The benefit of bilateral mastectomy for women with unilateral breast cancer in terms of deaths from breast cancer has not been shown.

Objectives听 To estimate the 20-year cumulative risk of breast cancer mortality among women with stage 0 to stage III unilateral breast cancer according to the type of initial surgery performed.

Design, Settings, and Participants听 This cohort study used the Surveillance, Epidemiology, and End Results (SEER) Program registry database to identify women with unilateral breast cancer (invasive and ductal carcinoma in situ) who were diagnosed from 2000 to 2019. Three closely matched cohorts of equal size were generated using 1:1:1 matching according to surgical approach. The cohorts were followed up for 20 years for contralateral breast cancer and for breast cancer mortality. The analysis compared the 20-year cumulative risk of breast cancer mortality for women treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. Data were analyzed from October 2023 to February 2024.

Exposures听 Type of breast surgery performed (lumpectomy, unilateral mastectomy, or bilateral mastectomy).

Main Outcomes and Measures听 Contralateral breast cancer or breast cancer mortality during the 20-year follow-up period among the groups treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy.

Results听 The study sample included 661鈥�270 women with unilateral breast cancer (mean [SD] age, 58.7 [11.3] years). After matching, there were 36鈥�028 women in each of the 3 treatment groups. During the 20-year follow-up, there were 766 contralateral breast cancers observed in the lumpectomy group, 728 contralateral breast cancers in the unilateral mastectomy group, and 97 contralateral cancers in the bilateral mastectomy group. The 20-year risk of contralateral breast cancer was 6.9% (95% CI, 6.1%-7.9%) in the lumpectomy-unilateral mastectomy group. The cumulative breast cancer mortality was 32.1% at 15 years after developing a contralateral cancer and was 14.5% for those who did not develop a contralateral cancer (hazard ratio, 4.00; 95% CI, 3.52-4.54, using contralateral breast cancer as a time-dependent covariate). Deaths from breast cancer totaled 3077 women (8.54%) in the lumpectomy group, 3269 women (9.07%) in the unilateral mastectomy group, and 3062 women (8.50%) in the bilateral mastectomy group.

Conclusions and Relevance听 This cohort study indicates that the risk of dying of breast cancer increases substantially after experiencing a contralateral breast cancer. Women with breast cancer treated with bilateral mastectomy had a greatly diminished risk of contralateral breast cancer; however, they experienced similar mortality rates as patients treated with lumpectomy or unilateral mastectomy.

Full Text

3 Comments for this article

EXPAND ALL

July 26, 2024

**Questioning the Necessity of Prophylactic Contralateral Mastectomy in Breast Cancer Patients

kefah mokbel, MBBS, MS, FRCS | London Breast Institute

Unfortunately this practice remains widespread (including he US) providing false reassurance and compromising QoL of patients.

Some cases of contralateral breast cancer represent reverse metastatic events, which can lead to increased mortality (1). Out breast homing hypothesis could partially explain the observations reported in the article.

References:

1. https://www.clinical-breast-cancer.com/article/S1526-8209(23)00263-X/pdf

CONFLICT OF INTEREST: None Reported

August 20, 2024

Role of bilateral mastectomy in unilateral breast cancer

Icro Meattini, Associate Professor, MD | Department of Experimental and Clinical Biomedical Sciences 鈥淢. Serio鈥�, University of Florence, Florence, Italy

The findings from the study by Giannakeas et al. (1), which examined long-term outcomes of bilateral mastectomy versus unilateral surgery for unilateral breast cancer, contribute significantly to the ongoing debate regarding the futility of contralateral risk-reducing mastectomy (RRM).
Although bilateral mastectomy significantly reduced the risk of contralateral breast cancer (CBC), and patients who developed CBC faced a twofold increase in mortality risk, the study did not demonstrate any impact on mortality over a 20-year period from RRM. Several factors could explain this lack of survival benefit. One possibility is that the number of CBC cases may not have been sufficient to influence overall survival statistics. Additionally, patient outcomes are often driven by the characteristics and treatment of the primary cancer rather than the CBC. It is also plausible that CBC is a marker of poor prognosis, reflecting an underlying aggressive disease biology, rather than directly contributing to poorer outcomes.
As a result, breast-conserving therapy (BCT) remains the recommended treatment approach for most early breast cancer patients, being potentially superior to mastectomy in most populations (2). While mastectomy may be clinically indicated in 20-30% of patients (3,4), the proportion undergoing mastectomy is increasing, even among those eligible for BCT. This choice for mastectomy often drives the demand for contralateral RRM, whether due to fear of cancer or a desire for symmetry and aesthetic appearance (5).
The SEER database used in the study does not include data on BRCA1 or BRCA2 mutation status, likely affecting 5-10% of the patients, as well as other populations at significant risk for CBC. The analysis also does not account for endocrine therapy or menopausal status after systemic therapy, factors known to influence CBC risk in patients with oestrogen receptor-positive tumours. These omissions could skew the results, particularly when evaluating the effectiveness of bilateral mastectomy across different breast cancer subgroups.
Despite these limitations, we congratulate the authors for their transparent discussion and recommendation for further research to identify women who may benefit from RRM. However, we caution our community, including patients, against misinterpreting the data showing reduced risks for CBC, as these reductions do not influence survival outcomes and may negatively impact quality of life. Therefore, RRM should only be considered in rare cases with significant genetic or clinical indications. The evolution of breast cancer management should continue to be guided by robust evidence, with careful consideration of risks and benefits, including patients鈥� health-related quality of life.

Icro Meattini, MD
University of Florence, Florence, Italy

Philip Poortmans, MD, PhD
University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium

Orit Kaidar-Person, MD
School of Medicine, Faculty of Medical & Health Sciences, Tel-Aviv University, Tel-Aviv, Israel

References
1. Giannakeas V, Lim DW, Narod SA. Bilateral Mastectomy and Breast Cancer Mortality. JAMA Oncol. 2024.
2. van Maaren MC, de Munck L, de Bock GH, et al. Lancet Oncol. 2016;17(8):1158-1170.
3. Gradishar WJ, Moran MS, Abraham J, et al. Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(6):691-722.
4. Rubio IT, Marotti L, Biganzoli L, et al. Eur J Cancer. 2024;198:113500.
5. Kummerow KL, Du L, Penson DF, Shyr Y, Hooks MA. JAMA Surg. 2015;150(1):9-16.

CONFLICT OF INTEREST: Icro Meattini reports occasional fees for advisory boards supported from Eli Lilly, Novartis, Pfizer, Astra Zeneca, Daiichi Sankyo, Gilead, SeaGen, Menarini StemLine, outside the submitted comment.

August 20, 2024

Bilateral Mastectomy and Breast Cancer Mortality

Steven Narod |

I thank the readers for their comments. The homing hypothesis proposed is one novel paradigm that attempts to reconcile the paradox that cancer prevention does not translate into mortality benefit. I have also explored this phenomenon in my new book entitled A Fair Trial: The Foundations of Breast Cancer which tries to reconcile these apparent paradoxes by invoking the parallel model of breast cancer progression.

CONFLICT OF INTEREST: None Reported

糖心vlog

Bilateral Mastectomy and Breast Cancer Mortality

Others Also Liked

Featured Articles

USPSTF Recommendation Statements

Blogs

糖心vlog

Bilateral Mastectomy and Breast Cancer Mortality

Read More About

Citation

Manage citations:

Others Also Liked

Select Your Interests