Population-based study of contralateral prophylactic mastectomy and survival outcomes of breast cancer patients

Abstract

Background: Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain.

Methods: We used the Surveillance, Epidemiology, and End Results database to identify 107 106 women with breast cancer who had undergone mastectomy for treatment between 1998 and 2003 and a subset of 8902 women who also underwent CPM during the same period. Associations between predictor variables and the likelihood of undergoing CPM were evaluated by use of chi(2) analyses. Risk-stratified (estrogen receptor [ER] status, stage, and age) adjusted survival analyses were performed by using Cox regression. Statistical tests were two-sided.

Results: In a univariate analysis, CPM was associated with improved disease-specific survival (hazard ratio [HR] of death = 0.63, 95% confidence interval [CI] = 0.57 to 0.69; P < .001). Risk-stratified analysis showed that this association was because of a reduction in breast cancer-specific mortality in women aged 18-49 years with stages I-II ER-negative cancer (HR of death = 0.68, 95% CI = 0.53 to 0.88; P = .004). Five year-adjusted breast cancer survival for this group was improved with CPM vs without (88.5% vs 83.7%, difference = 4.8%). Although rates of contralateral breast cancer among young women with stages I-II disease undergoing CPM were independent of ER status, women with ER-positive tumors in the absence of prophylactic mastectomy also had a lower overall risk for contralateral breast cancer than women with ER-negative tumors (0.46% vs 0.90%, difference = 0.44%; P < .001).

Conclusions: CPM is associated with a small improvement in 5-year breast cancer-specific survival mainly in young women with early-stage ER-negative breast cancer. This effect is related to a higher baseline risk of contralateral breast cancer.

Figure 1

Noncancer and cancer-specific survival for contralateral prophylactic mastectomy (CPM) vs no CPM by age at diagnosis. A) Noncancer survival associated with CPM among women aged 18–49 years at time of breast cancer diagnosis (hazard ratio [HR] for death = 0.62, 95% confidence interval [CI] = 0.36 to 1.06; P = .09). B) Cancer-specific survival associated with CPM among women aged 18–49 years at time of breast cancer diagnosis (HR for death = 0.84, 95% CI = 0.72 to 0.97; P = .02). C) Noncancer survival associated with CPM among women aged 50–59 years at time of breast cancer diagnosis (HR for death = 0.53, 95% CI = 0.32 to 0.87; P = .01). D) Cancer-specific survival associated with CPM among women aged 50–59 years at time of breast cancer diagnosis (HR for death = 0.79, 95% CI = 0.66 to 0.95; P = .01). E) Noncancer survival associated with CPM among women aged 60–90 years at time of breast cancer diagnosis (HR for death = 0.63, 95% CI = 0.53 to 0.74; P < .001). F) Cancer-specific survival associated with CPM among women aged 60–90 years at time of breast cancer diagnosis (HR for death = 0.88, 95% CI = 0.75 to 1.03; P = .13). The scale for x-axis is time after diagnosis in months. Adjusted for age, race, tumor stage, number of positive lymph nodes, tumor grade, tumor histology, and first tumor indicator in Cox regression model. All P values are two-sided and were calculated using the log-rank test.

Figure 2

Forest plot of risk-stratified hazard rates for disease-specific mortality associated with contralateral prophylactic mastectomy (CPM). Hazard ratios (HRs; solid circles) and 95% confidence intervals (shown by the whiskers on both sides of the solid circles) were derived by multivariable Cox regression analysis, adjusted for number of positive lymph nodes (0 vs 1–3 vs ≥4), tumor grade (1 vs 2 vs 3 vs 4), ethnicity and/or race (non-Hispanic white vs Hispanic white vs Black vs Asian or Pacific Islander vs other), tumor histology (nonlobular vs lobular), and first tumor indicator (yes vs no). All P values were calculated using Cox regression with the Wald test for significance. All P values were two-sided. ER = estrogen receptor.

Figure 3

Adjusted breast cancer–specific survival function associated with contralateral prophylactic mastectomy (CPM) for young women with early-stage breast cancer. A) Women with estrogen receptor (ER)–positive tumors (hazard ratio [HR] for death = 0.88, 95% confidence interval [CI] = 0.66 to 1.17; P = .38). B) Women with ER-negative tumors (HR for death = 0.68, 95% CI = 0.53 to 0.88; P .004). Hazard ratios and 95% confidence intervals were derived by multivariable Cox regression analysis, adjusted for number of positive lymph nodes (0 vs 1–3 vs ≥4), tumor grade (1 vs 2 vs 3 vs 4), ethnicity and/or race (non-Hispanic white vs Hispanic white vs Black vs Asian or Pacific Islander vs other), tumor histology (nonlobular vs lobular), and first tumor indicator (yes vs no). Percentages of women alive within the CPM and non-CPM groups at 3, 5, and 7 years are indicated on the curves. All P values are two-sided and were calculated using Cox regression with the Wald test for statistical significance.