Breast cancer researchers around the world are working to answer questions on cutting-edge research that will inform clinical trial design and guide treatment decisions in the future. At the 2024 San Antonio Breast Cancer Symposium^®, a panel of internationally renowned experts will explore two of today’s hottest topics in translational medicine — how to define triple-negative breast cancer and tumor agnostic drug development.

Translational Controversies will take place on Wednesday, December 11, from 2 to 3 p.m. CT in the Stars at Night Ballroom 1-2 at the Henry B. Gonzalez Convention Center. Antonio Wolff, MD, Professor of Oncology at Johns Hopkins University and Interim Director, Breast & Gynecologic Malignancies Group at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, will serve as moderator for the session.

“These two topics are not necessarily controversial in and of themselves, but the accelerated evolution of research and knowledge in these areas create challenges and many questions about how we build clinical trials in oncology and how we approach the treatment of patients with a breast cancer diagnosis,” Dr. Wolff said. “We have an amazing group of speakers who will discuss the latest research in these areas and how that research is translating into clinical practice.”

Topic 1: How to Define Triple-Negative Breast Cancer

Discussants:

• Rebecca Dent, MD, Head and Senior Consultant in the Department of Medical Oncology, National Cancer Centre Singapore, and Associate Professor at Duke-NUS Medical School, Singapore
• Charles Perou, PhD, Professor in the Department of Genetics and Co-Director of the Computational Medicine Program at the University of North Carolina at Chapel Hill, Faculty Director of the Lineberger Comprehensive Cancer Center (LCCC) Bioinformatics Group, and Co-Director of the LCCC Breast Cancer Research Program

“This topic is important because we make diagnoses and initial clinical decisions based on traditional breast cancer phenotypes, primarily identified on the basis of three immunohistochemistry biomarkers — expression of the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 receptor, along with different measures of tumor proliferation,” Dr. Wolff said.

This allows clinicians, he said, to identify tumors and guides their decisions about treatment on the basis of prognosis and likelihood of therapeutic benefits, in both the early-stage setting and in the metastatic setting, in ER-positive breast cancer, HER2-positive breast cancer, and triple-negative breast cancer.

“What makes triple-negative breast cancer so challenging is that by calling it triple-negative, what we are really doing is acknowledging that we don’t know what it is,” Dr. Wolff said. “We know that those tumors are not dependent on the ER or addicted to the HER2 pathways, but we really don’t immediately understand exactly what is driving these tumors.

“Our speakers on this topic will talk about what we currently do know about several potential targets and therapies beyond traditional cytotoxic drugs, and the potential additional markers that could help us better identify tumors and individualize the care of patients that are often simplistically labeled as having ‘triple-negative’ disease,” he said.

Topic 2: Tumor-Agnostic Drug Development

Discussants:

• Funda Meric-Bernstam, MD, Chair of the Department of Investigational Cancer Therapeutics, and Medical Director of the Institute for Personalized Cancer Therapy at The University of Texas MD Anderson Cancer Center
• Fabrice André, MD, PhD, Director of Research and Consultant Medical Oncologist in Breast Cancer at Gustave Roussy Cancer Center in Villejuif, France, and Professor of Medicine at Université Paris-Saclay in Orsay

“The idea of tumor agnostic drug development reflects an evolution and a new understanding that complements the historical major role that anatomy has played in medical education, clinical research, and how we organize subspecialty patient care, in the sense that cancers are often treated according to the organs of origin,” Dr. Wolff said. “This is a challenging and fascinating topic in a fast-paced area of research where we’ve seen a lot of changes and a lot of progress over the last several years.”

Research that led to the development of drugs, such as immune checkpoint modulators like pembrolizumab, he said, have demonstrated the potential of treatments that can target tumor and microenvironment interactions that are less dependent on tumor phenotype or the anatomic and histologic designation of the primary tumor.

“This additionally showed us that many molecular events in driving cancer evolution are shared across various tumor types, which could inform treatments beyond the underlying primary histologic diagnosis of breast cancer, pancreatic cancer, or ovarian cancer,” Dr. Wolff said.

He noted this suggests that the same treatment could theoretically be given to patients with different types of tumors if those tumors carry a similar molecular signature and are dependent on those pathways.

“It is important for us now to figure out what additional tests using tissue, imaging, or blood the clinician taking care of patients or the researcher designing clinical trials need to consider that will enhance and complement the work of expert pathologists, help us design more relevant and informative clinical trials, and ultimately make better clinical decisions for our patients,” Dr. Wolff said.