Although there is an approved immunotherapy for patients with triple-negative breast cancer, there has been little progress in developing immunotherapies for estrogen receptor-positive (ER+) subtypes.

During the 2024 San Antonio Breast Cancer Symposium®, Educational Session 10: Immunotherapy will explore how immunotherapy may expand its reach and look at the tools physicians can use to make therapeutic selections. The session will take place on Thursday, December 12, from 3:30 to 5:15 p.m. CT in Stars at Night Ballroom 1-2 at the Henry B. Gonzalez Convention Center.

“The session is going to be really terrific,” said session moderator Heather McArthur, MD, MPH, Professor of Internal Medicine at UT Southwestern Medical Center. “The speakers are all very active in this space, and I think we will have some interesting thoughts about the future of immunotherapy for estrogen receptor-positive disease, as well as for triple-negative disease.”

One of the most aggressive and difficult-to-treat types of breast cancer, triple-negative breast cancer is more common in younger women, Black women, and women with BRCA gene mutations. Pembrolizumab is approved in the neoadjuvant setting for patients with triple-negative disease. Marleen Kok, MD, PhD, Medical Oncologist and Group Leader at Netherlands Cancer Institute, will be speaking during the session on lessons learned in triple-negative disease and applying that to ER+ disease, as well as on future optimization of treatment in triple-negative breast cancer.

Cesar A. Santa-Maria, MD, MSCI, Associate Professor of Oncology at Johns Hopkins School of Medicine, will speak specifically about ER+ disease, including existing and novel data on the addition of immune checkpoint inhibitors to chemotherapy for both luminal A and luminal B subtypes. He will review the current research landscape, including trials that examined the effects of adding a checkpoint inhibitor to chemotherapy.

Dr. Santa-Maria will also discuss novel biomarkers in ER+ disease and use of CDK4/6 inhibitors as a way to prime tumors for the effects of immunotherapy.

“Preliminary studies in the highest risk ER+ breast cancers based on MammaPrint testing are showing pathologic complete response rates for immunotherapy with chemotherapy on par with what is seen in triple-negative disease,” Dr. Santa-Maria explained. “So based on that data, we’ve designed a study through the Southwest Oncology Group (SWOG 2206, NCT06058377) that will prospectively validate MammaPrint-determined high risk as an integral biomarker for therapeutic efficacy.”

For those patients with the luminal A subtype of ER+ disease, the most common type of ER+ breast cancer, Dr. Santa-Maria will provide an overview of tumor immune environment modulation using CDK4/6 inhibitors. CDK4/6 inhibitors can potentially increase PD-L1 expression, which could make the disease more susceptible to treatment with immunotherapeutic agents.

An important point to note regarding the use of CDK4/6 inhibitors in combination with immunotherapy, however, is that certain CDK4/6 and PD1 inhibitors have more toxicity and have resulted in high lung and liver inflammation.   

“I do think pursuing this combination needs to be done very carefully, but holds tremendous promise,” Dr. Santa-Maria stressed.

The session will also address other interesting combinations of immunotherapy outside of those used in ER+ disease, including various combinations with antibody-drug conjugates. Evanthia Roussos Torres, MD, PhD, Assistant Professor of Medicine and Biochemistry & Molecular Medicine at the University of Southern California Keck School of Medicine, will examine the future of immunotherapy, highlighting some of the intriguing questions that current trials have raised and offering insights about future directions.

“My prediction is that there will be a future FDA approval for immunotherapy for early-stage estrogen receptor-positive disease,” Dr. McArthur posited. “We need to start thinking about how we will reconcile that potential approval with current standard-of-care treatment.”