Biologic therapy for advanced breast cancer: recent advances and future directions

Advanced breast cancer (ABC) is a leading cause of mortality, morbidity, and disability in women worldwide. For decades, treatment of ABC has relied on chemotherapy and endocrine treatments (ET), until HER2 was recognized as a 'druggable' target in the 1990s. Thereafter, various anti-HER2 drugs have been approved for the HER2-positive subtype, but only in the last few years, biologic agents targeting different pathways have entered the therapeutic arsenal of luminal and triple-negative cancers.

The purpose of the present review is to recapitulate the most promising novel biologic agents being developed for the treatment of ABC. New drugs for all breast cancer subtypes are discussed, as well as some potential future directions in ABC treatment.

Several biologic drugs have been recently approved, revolutionizing ABC treatment algorithms: key examples are CDK4/6-inhibitors and the PI3K-inhibitor alpelisib for endocrine-positive ABC; atezolizumab for triple-negative cancers; two PARP-inhibitors for HER2-negative germinal BRCA-mutated cancers. Additionally, multiple drugs are demonstrating activity in late-phase clinical trials for all subtypes. While some of these represent pharmacological evolutions of previously approved drugs, some others might pave the way for new paradigms in ABC, challenging both its classification and current treatment algorithms.