Endocrine therapy is the mainstay in management of estrogen receptor-positive (ER+), human epidermal growth factor negative (HER2-) breast cancer, but a subset of tumors develops mutations in the estrogen receptor gene (ESR1) that confers endocrine resistance, particularly to aromatase inhibitors. A State-of-the-Art Session at 2023 SABCS® will review the latest advances and strategies to target ESR1-mutant breast cancer, including novel selective estrogen receptor degraders (SERDs) and selective estrogen receptor modifiers (SERMs).

“Currently, elacestrant is the only oral drug approved for ER+, HER2- metastatic ESR1-mutated breast cancer,” said Aditya Bardia, MD, MPH, Director of Breast Cancer Research at Massachusetts General Hospital Cancer Center, Associate Professor, Medicine, Harvard Medical School and principal investigator of several clinical trials examining the role of targeted therapy combinations for breast cancer. “However, other ESR1-targeting drugs are being developed to provide additional options for patients with this type of breast cancer. Among these are additional SERDs as well as SERMs, a class of drugs that has been used to target treatment-resistant estrogen receptors for a number of years.”

Dr. Bardia will moderate State-of-the-Art Session 3: Targeting Mutant ER. The session will take place from 1:30 p.m.–2:30 p.m. Friday, December 8 in Hemisfair Ballroom 1–2.

Following Dr. Bardia’s opening remarks, Geoffrey L. Greene, MD, PhD, Chair and Virginia and D.K. Ludwig Professor of the Ben May Department of Cancer Research, University of Chicago, will discuss the pros and cons of SERDs versus SERMs for targeting ESR1 mutations. A number of SERMs have come into use since tamoxifen was approved by the FDA in 1977. The SERM lasofoxifene is now in clinical trials to determine its efficacy at targeting ESR1 mutations. A primary focus of Dr. Greene’s research is on hormone-dependent cancers, including the identification and characterization of novel compounds including SERDs and SERMs.

A breast cancer researcher focused on blood biomarkers in the metastatic process including circulating tumor DNA (ctDNA), François-Clément Bidard, MD, PhD, Professor of Medicine, Department of Medical Oncology, Institut Curie & UVSQ/Université Paris-Saclay, will discuss how ctDNA assays are being used to guide the targeting of mutant estrogen receptors such as ESR1.  

The FDA approved the Guardant360 CDx ctDNA companion diagnostic assay at the same time this year that it granted approval to elacestrant. Other ctDNA assays are also in use.

The session will wrap up with a presentation on the future of oral SERDs by Erica P. Hamilton, MD, Director, Breast and Gynecological Cancer Research Program, Sarah Cannon Research Institute of HCA Healthcare, Nashville, who is involved in drug development and leading a number of studies of drugs that target women’s cancers.

While the SERD fulvestrant has been in limited use since its FDA approval in 2002 due in part to patient difficulty with its intramuscular formulation and once-monthly injection in large volumes, elacestrant is the first oral SERD that went through a randomized phase III trial showing increased efficacy, especially in tumors bearing ESR1 mutation. Elacestrant also demonstrated good tolerability. A number of other oral SERDs are in various stages of development.  

“This will be an important session reviewing a hot topic both from diagnostic and therapeutic perspectives,” said Dr. Bardia. “We need much more education on understanding genomics and treating endocrine-resistant breast cancer based on biomarkers.”

In addition to medical oncologists and other providers who treat breast cancer, Dr. Bardia emphasized that the session would be of interest to patient advocates and industry representatives.