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Double mastectomy decreased mortality among women with BRCA mutations
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Women with early-stage, BRCA-associated breast cancer who underwent double mastectomy were significantly more likely to survive than women who only had one breast removed, according to results of a retrospective analysis.
“For those who have been treated in the past with unilateral mastectomy or breast-conserving surgery, the possibility of a second surgery should be discussed,” the researchers wrote.
Women who carry a BRCA1 or BRCA2 mutation have a 60% to 70% lifetime risk for developing breast cancer. Once these women are diagnosed with breast cancer, they are at high risk for a second primary breast cancer, according to background information in the study.
Researchers assessed 20-year outcomes in 390 women diagnosed with early-stage breast cancer between 1975 and 2009. All women were known carriers of BRCA1 or BRCA2 mutations.
The women underwent single (n=346) or double mastectomy (n=44) as initial treatment. Of those in the single mastectomy group, 137 underwent contralateral mastectomy at a later date. Median time to contralateral mastectomy was 2 years).
At the 20-year follow-up, researchers reported 18 deaths occurred in the double mastectomy group and 61 deaths in single mastectomy group. The survival rate for those who underwent contralateral mastectomy was 88% (95% CI, 83-93) compared with 66% among women who did not undergo contralateral mastectomy (95% CI, 59-73).
Results from multivariable analysis controlled for age at diagnosis, year of diagnosis, treatment and other prognostic factors showed contralateral mastectomy was associated with a 48% decrease in breast cancer mortality (HR=0.52; 95% CI, 0.29-0.93). However, when researchers conducted a propensity score-adjusted analysis of 79 matched pairs, this association was not significant (HR=0.60; 95% CI, 0.34-1.06).
“It is reasonable to propose that bilateral mastectomy as the initial treatment option for women with early-stage breast cancer who are carriers of a BRCA1 or BRCA2 mutation,” the researchers concluded.
In an accompanying editorial, Karin Michels, MD, of Harvard Medical School, said larger studies designed to further explore this issue “will undoubtedly be generated” in the near future. However, the choice to undergo single or double mastectomy remains a difficult one.
“The decision to undergo a bilateral mastectomy is an individual and personal choice that a woman has to make together with her doctor,” Michels wrote. “A woman needs to weigh up alternative options, including regular close monitoring and the use of tamoxifen or raloxifene, while considering the opportunities but also possible complications of reconstructive surgery. No statistics and no statistician can make this decision for her.”
For more information:
- Metcalfe K. BMJ. 2014;doi:10.1136/bmj.g226.
- Mitchels KB. BMJ. 2014;doi:10.1136/bmj.g1379.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Doreen Agnese, MD
Care must be exercised when interpreting the results of retrospective studies, because it is impossible to control for selection bias and the study size is quite small. The results, however, are intriguing.The authors extended follow-up to 20 years, as shorter follow-up periods may not assess the contribution of second primary cancers, which would likely not impact survival in the first 10 years after diagnosis of the initial cancer. A significant survival advantage was noted in women who had contralateral mastectomy.
Although it is impossible to know which breast cancer specifically resulted in a patient’s death, the knowledge suggests that most of the deaths that occurred in the second decade after initial diagnosis were in patients diagnosed with a contralateral primary. Prospective randomized data addressing this issue would certainly provide better evidence to support a survival advantage with contralateral mastectomy, but this trial will never be done.
This study has important implications in the treatment of individuals with hereditary predisposition to breast cancer. I agree that it is reasonable to discuss bilateral mastectomy as an initial treatment for carriers of a BRCA1 or BRCA2 mutation with unilateral early-stage breast cancer, and to consider it in a delayed fashion once information regarding mutation status is available in those previously treated. This procedure will certainly decrease the incidence of contralateral breast cancer diagnosis, and it seems may impact survival after all.
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