Findings from a large study have challenged the assumption that contralateral prophylactic mastectomy improves survival in women with unilateral breast cancer, despite reducing contralateral breast cancer risk.
The study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) Program registry on 661,270 women diagnosed with unilateral breast cancer (invasive and ductal carcinoma in situ) between 2000 and 2019. The findings were published in JAMA Oncology. The researchers generated three closely matched cohorts of 36,028 women each, based on surgical approach: lumpectomy, unilateral mastectomy, or bilateral mastectomy.
Over a 20-year follow-up period, 766 contralateral breast cancers were observed in the lumpectomy group, 728 in the unilateral mastectomy group, and 97 in the bilateral mastectomy group. The 20-year risk of contralateral breast cancer was 6.9% in the combined lumpectomy and unilateral mastectomy groups, with an annual risk of 0.3% per year.
The cumulative risk of contralateral breast cancer was slightly higher for patients with ductal carcinoma in situ (DCIS) compared to those with invasive cancer (8.2% vs 6.8%, respectively). The 20-year cumulative risk of contralateral breast cancer was 6.7% for patients with ductal disease, 7.1% for patients with lobular disease, and 8.0% for those with mixed histologic findings.
Notably, the cumulative breast cancer mortality was 32.1% at 15 years in those who developed a contralateral cancer, compared with 14.5% for those who did not develop a contralateral cancer (hazard ratio [HR], 4.00; 95% confidence interval [CI], 3.52-4.54). The hazard ratio for dying of breast cancer after experiencing a contralateral breast cancer was higher for women initially treated for DCIS (HR, 10.30; 95% CI, 5.17-20.49) than for women initially treated for invasive cancer (HR, 4.04; 95% CI, 3.54-4.60).
However, despite the reduced risk of contralateral breast cancer, the 20-year breast cancer−specific mortality was similar across the three groups: 16.3% in the lumpectomy group, 16.7% in the unilateral mastectomy group, and 16.7% in the bilateral mastectomy group. The 20-year mortality from lobular cancer was higher than that for patients with ductal or mixed histologic findings, and it was also higher for patients with ER-negative breast cancer compared to ER-positive disease.
The study's strengths included its large, contemporary population-based cohort and long follow-up period. Limitations included the lack of data on endocrine therapy use, family history, and BRCA1/2 mutation status, which may affect contralateral breast cancer risk.
The authors concluded that while bilateral mastectomy effectively reduced contralateral breast cancer risk, it did not improve breast cancer−specific survival compared with unilateral surgery. These findings called into question the metastatic potential of de novo contralateral breast cancers and emphasized the importance of providing accurate risk and benefit information to patients considering bilateral mastectomy for unilateral breast cancer.
Conflict of interest disclosures are available in the study.
