SAN ANTONIO -- Bilateral mastectomy as initial treatment for women with breast cancer and a pathogenic BRCA1 variant was not linked to better survival, according to an international analysis.
Compared with breast-conserving treatment (BCT), bilateral mastectomy was not significantly associated with a reduction in mortality in this population of patients (HR 0.83, P=0.52), reported Kelly Metcalfe, RN, PhD, of Women's College Research Institute in Toronto, during the San Antonio Breast Cancer Symposium.
Rates of 15-year breast cancer-specific survival were 86.2% with BCT, 78.7% with unilateral mastectomy, and 88.7% with bilateral mastectomy. On multivariate analysis, the hazard ratio for mortality in the group who underwent unilateral mastectomy versus BCT was 1.22 (95% CI 0.92-1.62), and was 0.88 (95% CI 0.58-1.13) for those who underwent bilateral mastectomy versus BCT.
However, women who underwent bilateral mastectomy were significantly less likely to be diagnosed with contralateral breast cancer during follow-up -- 0.8% versus 10.8% in the BCT group and 11.4% in the unilateral mastectomy group (P<0.0001).
On multivariate analysis, women who developed contralateral breast cancer were twice as likely to die (HR 2.22, P<0.0001), with a significantly increased risk of mortality regardless of age at diagnosis.
Germline genetic testing is increasingly being integrated into clinical care for women with breast cancer. "These women are often offered genetic testing prior to the initiation of any treatment," said Metcalfe. About 3% to 4% of women with breast cancer have a germline BRCA1 or BRCA2 mutation, "and based on these genetic test results, treatment can then be personalized for an individual patient."
"When we're thinking about treatment for these patients, we're thinking about treating that index cancer but we're also thinking about their increased risks of developing both an ipsilateral and contralateral breast cancer, as well as their very high lifetime risk of developing ovarian cancer," she added.
Brian Czerniecki, MD, PhD, of the Moffitt Cancer Center in Tampa, Florida, told 51˶ that the data don't change his recommendation for bilateral mastectomy for women with a BRCA1 pathogenic variant, especially younger patients, due to their high risk of developing a second cancer.
"Bilateral mastectomy will help prevent a second cancer, which will improve their life expectancy," he said, adding that any subsequent cancers that develop are likely to be triple-negative breast cancers (TNBC), which are more difficult to treat.
Metcalfe and colleagues used data from medical records and included 2,482 women from 26 centers in 11 countries. Eligible participants had a diagnosis of stage I-III breast cancer and a documented BRCA1 pathogenic variant. Mean age at diagnosis was 43.1 years.
Of these patients, 34.3% underwent BCT, 46% underwent unilateral mastectomy, and 19.7% underwent bilateral mastectomy. The bilateral mastectomy group was significantly younger at diagnosis (mean age 41.3 years) compared with the other two groups (mean age 43.5 years in each group; P<0.0001).
Number of follow-up years was also significantly fewer for the women who underwent bilateral mastectomy (6.5 years) compared with those who underwent BCT (9.2 years) and unilateral mastectomy (9.6 years).
Women who elected to have bilateral mastectomy were significantly more likely to have oophorectomy, whereas those who chose BCT or unilateral mastectomy were significantly more likely to receive radiation therapy, chemotherapy, and tamoxifen.
Of the total participants, 11.5% died of breast cancer over a mean follow-up of 8.9 years, and the overall 15-year breast cancer-specific survival was 82.9%.
The investigators are continuing to accrue data, with a predicted sample size eventually reaching 6,000, said Metcalfe. "We need longer follow-up for these women, especially as we're considering the time it takes in between the index cancer and the contralateral breast cancer," she noted.
Newer treatments such as olaparib (Lynparza) and the benefit of oophorectomy, which has been shown to be protective against mortality, should also be considered. Metcalfe said her research group is expanding the patient population to include women with germline mutations in PALB2, TP53, and ATM.
Disclosures
Metcalfe disclosed a financial relationship with AstraZeneca.
Primary Source
San Antonio Breast Cancer Symposium
Metcalfe KA, et al "Surgical treatment of women with breast cancer and a BRCA1 pathogenic variant: an international analysis of the impact of bilateral mastectomy on survival" SABCS 2023.