Significant progress has been made in recent years for the treatment of postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC).

In the first-line setting, fulvestrant alone or in combination with an aromatase inhibitor (AI) has been shown to be superior to an AI alone, whereas combinations of endocrine therapy (ET) plus a cyclin-dependent kinase (CDK)4/6 inhibitor has increasingly become the new standard of care.

Combinations of ET plus CDK4/6 or mammalian target of rapamycin inhibitors have been approved in the ET-resistant setting.

Recent approval of alpelisib with fulvestrant in phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutated HR+, HER2− MBC following progression on or after ET marks the first combination therapy approved based on somatic mutations in MBC.

The role for genomic biomarkers in guiding individualized treatment of HR+, HER2− MBC is expanding.