Among early-stage breast cancer patients who carry BRCA mutations, prophylactic mastectomy of the contralateral breast appears to reduce the risk of dying from breast cancer within 20 years by 48%, according to a report published online Feb. 11 in the British Medical Journal.
This significant mortality benefit is most pronounced during the second decade after the initial breast cancer diagnosis, said Dr. Kelly Metcalfe of the University of Toronto, and her associates.
"We conclude that it is reasonable to propose bilateral mastectomy as the initial treatment option for women with early-stage breast cancer who are carriers of a BRCA1 or BRCA2 mutation. 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," they said.
Until now, the data regarding long-term survival after prophylactic mastectomy have been sparse, and no study has examined mortality specifically related to mastectomy of the contralateral breast. "Traditionally, breast cancer trialists and clinical epidemiologists focus their attention on the 10-year period after diagnosis, because this is when the majority of cancer-related deaths occur. However, a mortality benefit from preventing a second primary breast cancer is unlikely to be apparent within this narrow interval, given that second primary cancers accumulate slowly and for an extended period," Dr. Metcalfe and her colleagues said.
They reviewed the medical records and pathology reports of 390 women who had been diagnosed as having stage I or II breast cancer in 1975-2009 when they were aged 65 or younger, were known or likely carriers of a deleterious mutation in the BRCA1 or BRCA2 gene, and were treated with unilateral or bilateral mastectomy. These study participants were identified from the histories of 290 different families in which one member had received genetic counseling at any of 12 specialty clinics.
A total of 44 of the women were initially treated with bilateral mastectomy. The remaining 346 initially underwent unilateral mastectomy, but 137 of them went on to have mastectomy of the contralateral breast at a later time. Thus, in the final analysis 181 women had prophylactic mastectomy of the contralateral breast and 209 did not.
The mean follow-up was 13 years (range, 0.1-20.0 years).
Overall, 79 women (20% of the entire study population) died from breast cancer during follow-up: 18 of the 181 women who had prophylactic mastectomy of the contralateral breast (9.9%), compared with 61 of 209 who did not have prophylactic mastectomy (29.1%).
At 20 years, the survival rate for women who underwent prophylactic mastectomy was 88%, compared with a 66% survival rate among those who did not have prophylactic mastectomy of the contralateral breast.
In a multivariable analysis that controlled for age at diagnosis, tumor size, nodal status, treatment, and other prognostic factors, 20-year breast-cancer-specific mortality was 48% lower for those who underwent contralateral mastectomy than for those who did not (hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P = .03), the investigators wrote (Br. Med. J. 2014 Feb. 11 [doi:10.1136/bmj.g226]).
The reduction in mortality was much greater during the second decade of follow-up (80% reduction) than during the first decade (35% reduction). "On average, the time from first breast cancer to ... cancer of the contralateral breast is 5.7 years. Therefore, a delay in the observed benefit of contralateral mastectomy is to be expected – that is, the reduction in mortality results from a reduction in deaths from cancer of the contralateral breast," Dr. Metcalfe and her associates said.
They noted that it is critical that these findings be confirmed in other study populations, especially in view of their relatively small study population.
This study was funded by the Canadian Breast Cancer Foundation. Dr. Metcalfe is supported by the Canadian Institutes of Health Research and the Ontario Women’s Health Council. No financial conflicts of interest were reported.