Contralateral prophylactic mastectomy and its association with reduced mortality: evidence for selection bias

Contralateral prophylactic mastectomy (CPM) refers to removal of the opposite uninvolved breast in women with unilateral breast cancer, and rates are increasing worldwide. In observational studies, CPM is often associated with reductions in breast cancer-specific and all-cause mortality when compared to unilateral surgical treatment alone, but this may reflect selection of a healthier cohort for CPM (selection bias). To further explore this possibility, we examined the association between CPM and non-cancer mortality, an indicator of selection bias. We identified 449,178 adult women diagnosed with unilateral, primary American Joint Committee on Cancer (AJCC) stage I-III ductal or lobular breast cancer, utilizing the 1998-2010 Surveillance, Epidemiology, and End Results dataset. Of these, 5.8% (n = 25,961) underwent CPM as their first course of treatment. We examined associations between CPM and breast cancer-specific, all-cause, and non-cancer mortality utilizing multivariate logistic regression, adjusting for age, race, AJCC stage, estrogen receptor status, progesterone receptor status, and histologic grade of the tumor. Among all patients receiving CPM as first course of treatment, CPM was associated with lower breast cancer-specific [HR 0.84 (95% CI 0.79-0.89)], all-cause [HR 0.83 (95% CI 0.80-0.88)], and non-cancer [HR 0.71 (95% CI 0.64-0.80)] 5-year hazard of death. Although our results are consistent with other observational studies showing associations between CPM and reductions in breast cancer-specific and all-cause mortality, we demonstrate an even stronger association between CPM and reduced non-cancer mortality. Thus, the reported associations between CPM and reductions in mortality might at least partly be attributable to selection bias.