There has been substantial interest in the impact of ATP-binding cassette (ABC) transporter variability on breast cancer drug resistance. Here, we provide a systematic review of ABC variants in breast cancer therapy. Notably, most studies used small heterogeneous cohorts and their identified associations lack statistical stringency, replication and mechanistic support. We conclude that commonly studied ABC polymorphisms are not suitable to accurately predict therapy response or toxicity in breast cancer patients and cannot guide treatment decisions. However, recent research shows that ABC transporters harbor a plethora of rare variants with individually small effect sizes, and we argue that a shift in strategy from target variant interrogation to comprehensive profiling might hold promise to drastically improve the predictive power of outcome models.
Keywords: anthracyclines; chemotherapy; drug resistance; drug transporters; personalized medicine; pharmacogenetics; precision oncology; taxanes.