Contralateral breast cancer doubles mortality risk among women with BRCA1 mutations
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Key takeaways:
- Contralateral breast cancer doubled breast cancer mortality risk for women with BRCA1 mutations
- These women should be counseled on contralateral breast cancer risk when making decisions about surgery.
SAN ANTONIO — Women with breast cancer who harbored a BRCA1 mutation and developed contralateral breast cancer had a mortality risk double that of women who did not develop contralateral breast cancer, according to study results.
Women who opted for bilateral mastectomy as initial treatment exhibited a small, statistically nonsignificant reduction in mortality, findings presented at San Antonio Breast Cancer Symposium showed.
The findings suggest women with a BRCA1 mutation should be counseled regarding the risk for contralateral breast cancer before making decisions about surgery, investigators concluded.
“What we see from these data is that women with a BRCA1 pathogenic variant who elect for bilateral mastectomy are significantly less likely to develop a contralateral breast cancer, and that women with a BRCA1 mutation who develop a contralateral breast cancer are twice as likely to die of breast cancer,” Kelly Metcalfe, RN, PhD, professor at University of Toronto, said during a presentation. “However, bilateral mastectomy was not significantly associated with a reduction in mortality compared with women [who underwent] breast-conserving surgery.”
Background and methods
Women with breast cancer who harbor BRCA1 mutations have an elevated risk for contralateral breast cancer. This prompts some women with unilateral breast cancer to opt for bilateral mastectomies.
Some women also may undergo contralateral prophylactic mastectomy as a second surgery; however, limited data exist regarding how this potentially affects breast cancer mortality.
Metcalfe and colleagues evaluated differences in survival by surgical treatment among women with unilateral breast cancer and BRCA1 mutations.
The analysis included 2,482 women (median age, 43.1 years; range 18-70) treated at one of 26 centers in 11 countries for stage I, II or III breast cancer. Patients had breast-conserving surgery (n = 852), unilateral mastectomy (n = 1,141) or bilateral mastectomy (n = 489).
Exclusion criteria included stage IV breast cancer, ductal carcinoma in situ or synchronous bilateral breast cancer.
Results, next steps
Researchers reported a 27.5% risk for contralateral breast cancer at 20 years among patients who underwent unilateral mastectomy or lumpectomy.
Contralateral breast cancer appeared associated with a twofold increased risk for breast cancer death (HR = 2.14; 95% CI, 1.43-3.18).
In the entire cohort, results showed 15-year breast cancer-specific survival of 82.9%, with rates of 78.7% for those who underwent unilateral mastectomy, 86.2% among those who underwent lumpectomy and 88.7% among those who had bilateral mastectomy.
Researchers determined 529 women who initially underwent unilateral surgery later had contralateral or bilateral preventive mastectomy. Analyses adjusted for age at diagnosis, nodal status, tumor size, chemotherapy receipt and preventive mastectomy, results showed reduced risk for breast cancer mortality with bilateral surgery vs. unilateral surgery (HR = 0.78; 95% CI, 0.55-1.13).
“I think these data raise a lot of questions that we still need to answer,” Metcalfe said, noting this was an interim analysis and investigators hope to collect data on 6,000 patients. “We also need longer follow-up for these women, especially as we’re considering the time that it takes in between the index cancer and the contralateral breast cancer if we’re looking at survival from that contralateral breast cancer, as well,” she added.
Perspective
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Richard J. Bleicher, MD, FACS
This study evaluated a retrospective cohort from 26 centers in 11 countries to determine whether adding contralateral mastectomy improves survival for women with a BRCA1 mutation and unilateral breast cancer.
Specifically, researchers compared women who had unilateral mastectomy, lumpectomy or bilateral mastectomy. Interestingly, the patients who had a unilateral mastectomy had shorter survival than those who had lumpectomy. This is surprising, because many prospective randomized trials demonstrate that lumpectomy and mastectomy have identical survival — and this would not be expected to be different among women with BRCA mutations. The difference here likely represents selection bias, with the patients who underwent mastectomy having worse disease or factors that shortened their lifespan compared with those who underwent lumpectomy. That survival difference between unilateral mastectomy and lumpectomy was 7.5 percentage points, which is not insubstantial. Bilateral mastectomies provided an additional 2.5 percentage-point survival benefit over lumpectomy, or 10 percentage points over unilateral mastectomy. Ultimately the HR for bilateral surgery vs, any unilateral surgery showed a 22% survival benefit. Moreover, those who experienced a contralateral cancer had an HR for breast cancer death of 2.14.
Things to keep in mind: The HR for those having a second cancer sounds large, as it is a relative “doubling” of the risk for death, but we do not see the absolute risk for death in the setting of those who developed a second cancer. The absolute values are important to show. For instance, doubling of 1% is different than doubling of 40%. Moreover, the primary question is whether doing a contralateral mastectomy prophylactically provides a survival benefit — which means doing that mastectomy before the development of the contralateral cancer (which is what this doubling statistic refers to). And in that case, there is only a 2.5 percentage point survival benefit over lumpectomy and 10 percentage points over mastectomy.
I think the authors correctly stated we need longer follow-up. Hopefully the presentation will allow us to determine whether the various cohorts are significantly different, providing selection bias. It would not be acceptable to do a study where you randomly assign women to removing their contralateral breast or not to objectively assess the added survival value, and so retrospective series like this one will need to suffice in this setting. Ultimately, I would say the this study does not change our paradigms based upon what we see here so far.
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Metcalfe K, et al. Abstract GS02-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2023; San Antonio.
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