Breast cancer therapy for BRCA1 carriers: moving towards platinum standard?

Abstract

Recently Byrski et al. reported the first-ever breast cancer (BC) study, which specifically selected BRCA1-carriers for the neoadjuvant treatment and used monotherapy by cisplatin instead of conventional schemes. Although the TNM staging of the recruited patients was apparently more favorable than in most of published neoadjuvant trials, the results of Byrski et al. clearly outperform any historical data. Indeed, 9 of 10 BRCA1-associated BC demonstrated complete pathological response to the cisplatin treatment, i.e. these women have good chances to be ultimately cured from the cancer disease. High sensitivity of BRCA1-related tumors to platinating agents has been discussed for years, but it took almost a decade to translate convincing laboratory findings into first clinical observations. With increasing stratification of tumor disease entities for molecular subtypes and rapidly growing armamentarium of cancer drugs, it is getting technically and ethically impossible to subject all promising treatment options to the large randomized prospective clinical trials. Therefore, alternative approaches for initial drugs evaluation are highly required, and one of the choices is to extract maximum benefit from already available collections of biological material and medical charts. For example, many thousands of BC patients around the world have already been subjected to second- or third-line therapy with platinum agents, but the association between BRCA status and response to the treatment has not been systematically evaluated in these women. While potential biases of retrospective studies are widely acknowledged, it is frequently ignored that the use of archival collections may provide preliminary answers for long-standing questions within days instead of years. However, even elegantly-designed, small-sized, hypothesis-generating retrospective studies may require multicenter efforts and somewhat cumbersome logistics, that may explain the surprising lack of historical data on the platinum-based treatment of BC in BRCA1 carriers.