Recent Developments in Treatment Stratification for Metastatic Breast Cancer

Abstract

The modern approach to management of metastatic breast cancer (MBC) is centred on individualizing treatment to best suit the patient's breast cancer characteristics (molecular subtype, disease burden and prognostic markers), as well as the patient's clinical history (co-morbidities, prior therapies and social factors). The wealth of treatments available has heightened the complexity of tailored patient care that in turn allows better optimization of treatment efficacy and quality of life. There are promising developments in the management of estrogen receptor (ER)-positive breast cancer, particularly with respect to overcoming resistance with dual targeting of the phosphoinositide-3 kinase/AKT/mammalian target of rapamycin and ER-signalling pathways. A central focus in the management of triple negative breast cancer has been through efforts to identify novel therapeutic targets in this disease subgroup. Next-generation sequencing approaches have begun to reveal how breast cancer somatic mutational heterogeneity between tumours with the same histopathological subtype is likely to impede efforts to identify novel common therapeutic targets. The most successful example of targeted therapy in MBC is the targeting of human epidermal growth factor receptor 2 (HER2) by trastuzumab. Dual and irreversible HER2/epidermal growth factor receptor targeting and attenuation of downstream resistance pathways also appear promising in HER2-positive trastuzumab-refractory breast cancer. Targeted therapy with antiangiogenic agents shows clinical activity, but the balance between efficacy, toxicity and cost remains a topic of debate, emphasizing the unmet need for a predictive biomarker of response to this class of drug. Poly(ADP ribose) polymerase(PARP) inhibitors appear to have clinically meaningful activity in BRCA germline mutant breast cancer. Activity of PARP inhibitors in other breast cancer subgroups is yet to be clearly defined. Novel chemotherapy agents show marginally superior efficacy, at a cost of a moderate increase in toxicity. Bone-modifying drugs expand supportive care options; again, better permitting individualization of treatment choice. The future management of MBC will increasingly focus on stratifying therapeutics based on individualized-tumour molecular aberrations.