The panel shifts to treatment strategies for patients with hormone receptor-positive, HER2-negative metastatic breast cancer (HR+/HER2− mBC) who develop an ESR1 mutation after progression on an aromatase inhibitor plus CDK4/6 inhibitor. Dr. Erica Mayer reviews the growing role of oral selective estrogen receptor degraders (SERDs) and other novel endocrine therapies, explaining how ESR1 mutations can lead to constitutive estrogen receptor activity and reduce the effectiveness of estrogen-depleting aromatase inhibitors. She discusses available monotherapy approaches and emerging combination strategies that pair an oral SERD or other novel endocrine agent with a targeted therapy. Dr. Mayer notes that combination approaches may provide greater disease control by simultaneously targeting estrogen receptor signaling and additional resistance pathways, while monotherapy can remain appropriate for selected patients with slower-growing, lower-volume disease or greater concerns about treatment burden and tolerability. The discussion highlights how the expanding ESR1-directed treatment landscape is creating greater flexibility in second-line treatment selection for HR+/HER2− mBC.
