Dr. Graff on Current Treatments in ESR1-Mutant Breast Cancer

Stephanie L. Graff, MD, director of the Breast Program at the Sarah Cannon Cancer Institute of HCA Midwest Health and associate director of the Breast Cancer Research Program at Sarah Cannon Research Institute, discusses current treatments in ESR1-mutant breast cancer.

If a patient with metastatic hormone receptor-positive breast cancer progresses on frontline therapy and develops an ESR1 mutation, treatment options are limited, says Graff. Current standards are to adhere to national guidelines. However, according to data from the phase III PALOMA-3 trial, patients did not experience the same degree of benefit with palbociclib (Ibrance) and fulvestrant as those without the mutation.

Patients with ESR1 wild-type tumors had a much greater magnitude of benefit with the combination, adds Graff. Although the combination of a CDK4/6 inhibitor and endocrine therapy is recommended, more effective treatment options are needed. Lasofoxifene (Fablyn), a nonsteroidal selective estrogen receptor modulator, may be one such agent. The drug was granted a fast track designation by the FDA for use in patients with estrogen receptor-positive, ESR1-mutant metastatic breast cancer in May 2019, and is currently being evaluated in the ongoing phase II ELAINE trial.