Oral SERDs Transform Metastatic Breast Cancer Management: With Sara Nunnery, MD, MSCI; and Vandana G. Abramson, MD

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.

In this episode, Nunnery sat down with Vandana G. Abramson, MD, a professor of medicine, co-leader of the Breast Cancer Research Program, and the Breast Cancer Disease Team leader at Vanderbilt Health and the Vanderbilt-Ingram Cancer Center in Nashville.

They discussed the transformative effects of next-generation oral selective estrogen receptor degraders (SERDs) in hormone receptor–positive breast cancer management. Unlike treatments that block estrogen or prevent its production, SERDs work by completely degrading the ER, the experts explained. These oral treatment options are more effective and patient friendly than the standard intramuscular injection of fulvestrant (Faslodex), they contextualized.

A central theme in their conversation was the ESR1 mutation, an acquired resistance mechanism that makes the ER constitutively active, meaning it remains turned on regardless of treatment. They noted that approximately 40% to 50% of patients develop this mutation after long-term endocrine therapy use. Dr Abramson emphasized that liquid biopsies are the preferred method for detecting these mutations, as they provide a detailed picture of the disease across multiple metastatic sites.

The conversation also highlighted data from 2 major phase 3 trials, EMERALD (NCT03778931) and EMBER-3 (NCT04975308). Data from EMERALD led to the FDA approval of elacestrant (Orserdu) for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of endocrine therapy. The experts noted that although elacestrant is effective for a broad population of patients, it showed the strongest signal in patients with ESR1 mutations. Findings from EMBER-3 led to the FDA approval of imlunestrant (Inluriyo) for the treatment of adult patients with ER-positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations whose disease has progressed following 1 or more prior lines of endocrine therapy.

The experts reported that both drugs demonstrate manageable safety profiles. Common adverse effects include nausea and fatigue, but patients experience fewer arthralgias than with aromatase inhibitors, the experts noted. Future research is focused on moving oral SERDs into the adjuvant setting to potentially preserve bone density and improve outcomes for patients with early-stage disease, they concluded.