Updates to the Management of HR-Positive, HER2-Negative Breast Cancer

Metastatic hormone receptor–positive, HER2-negative breast cancer treatment is increasingly individualized as more of the tumor landscape is described and targeted therapies are developed. CDK4/6 inhibitors have demonstrated consistency in prolonging progression-free survival across several clinical trials in advanced disease. Research in endocrine therapy highlighted the noninferiority of fulvestrant compared with aromatase inhibitors after disease progression. Studies such as the PEARL and Young-PEARL trials challenged the superiority of chemotherapy over endocrine therapy in certain populations, including premenopausal women. Sequential CDK4/6 inhibitor therapy after disease progression showed potential benefits, though definitive data are lacking. Targeting the PI3 kinase pathway, particularly with capivasertib in patients with pathway alterations, showed significant improvements in progression-free survival. ESR mutations have been identified as a key factor in resistance to endocrine therapy, with elacestrant showing promise in overcoming this challenge. Finally, in early-stage cancer, the question of whether ovarian suppression along with endocrine therapy can show the same results as chemotherapy is being explored, but the answer remains to be seen.