Contralateral prophylactic mastectomy and survival: An ongoing challenge

As use of contralateral prophylactic mastectomy (CPM) continues to increase, the need to demonstrate oncologic benefit to patients undergoing this procedure becomes ever more important. Whereas CPM has consistently been shown to reduce the incidence of second, contralateral breast cancer events, demonstrating survival benefit from CPM has been more challenging. In this edition of the Annals of Surgical Oncology, Kruper et al. report on their attempt to answer this question by using data from SEER, the Surveillance, Epidemiology, and End Results database. They evaluated the outcome of 26,526 women who underwent CPM and 138,826 patients who underwent single mastectomy. After propensity score matched analysis, they found CPM was associated with improved disease-specific survival [hazard ratio (HR) 0.86, 95 % confidence interval (CI) 0.79–0.93] but a much greater improvement in overall survival (HR 0.76, 95 % CI 0.71–0.81); this pattern was seen in almost all subsets of patients examined. Since CPM decreases the risk of contralateral breast cancer, one would expect that CPM would have more of an effect on survival from breast cancer, that is disease-specific survival, as opposed to overall survival, which measures general overall health. They also found survival benefit to CPM across all stages of disease and across both estrogen receptor (ER)positive and ER-negative populations. Additionally, when they removed the women who would have benefitted the most from CPM, those women who had contralateral breast cancer, the HR for diseasespecific and overall survival did not change. They conclude that the reported survival benefits seen for CPM are the result of selection bias. Like many large observational databases, SEER has a number of shortcomings which are reflected in the results presented by Kruper and colleagues. SEER is not a national population registry, and patient movement in and out of registry zones will limit long-term data collection. SEER also does not collect family history and mutation status, thus limiting the ability to adjust for variables that affect the likelihood of contralateral breast cancer. Importantly for this study, SEER does not contain information on adjuvant hormonal therapy or chemotherapy, HER2 status or comorbid conditions; therefore, patients were not matched on several important variables that affect survival. Consequently, regardless of the use of propensity score matched analysis to balance the cohorts, the inability to account for known prognostic and therapeutic variables in the model limits the ability to minimize bias and distinguish subsets where survival association with CPM may be present. The conclusion that Kruper et al. put forward, namely, that bias is a key issue in the selection of patients for CPM, has also been raised in prior publications similarly using large observational databases. In a retrospective study from the Cancer Research Network, Herrinton et al. reported that CPM was associated with a 4 % absolute decrease in breast cancer mortality compared with women not undergoing CPM. However, much like the Kruper study, Herrinton and colleagues showed CPM to also improve overall survival, with a 7 % absolute decrease in all-cause mortality, thus raising concern that the CPM cohort represented a healthier group of women. Such women would have been more likely to also receive more aggressive treatment for their index malignancy, and this aggressive treatment, rather than the CPM, could have Society of Surgical Oncology 2014