Titles and Affiliations
Associate Director, Susan F. Smith Center for Women’s Cancers
Research area
Improving treatments for people with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer.
Impact
In a recent landmark clinical trial, the antibody-drug conjugate sacituzumab govitecan (Trodelvy®) was shown to be more effective than chemotherapy for patients with hormone receptor (HR)-positive, HER2-negative breast cancer that has developed resistance to endocrine therapy. Sacituzumab govitecan damages the DNA within cancer cells, drawing immune cells into the tumor. Studies suggest that pairing sacituzumab govitecan with immunotherapy may enhance the anti-tumor immune response. Dr. Tolaney is testing this combination therapy in patients with HR-positive, HER2-negative metastatic breast cancer.
Progress Thus Far
Over the past year, Dr. Tolaney and her team conducted a study evaluating whether combining sacituzumab govitecan, an antibody-drug conjugate, with the immunotherapy pembrolizumab could improve outcomes for patients with advanced breast cancer. While the combination did not significantly extend the time patients lived without their cancer progressing compared to sacituzumab govitecan alone, encouraging trends were seen in patients whose tumors expressed PD-L1, the target of pembrolizumab. In this group, participants treated with the combination lived longer before their cancer worsened. The team also examined Trop-2, a protein targeted by sacituzumab govitecan, but found that its expression level was not linked to patient outcomes.
What’s next
Next, Dr. Tolaney and her team will take a deeper look at tumor samples collected before and during treatment to better understand why some tumors respond to therapy while some do not. By analyzing DNA and RNA data, they aim to pinpoint genetic and molecular features linked to treatment response or resistance. They are also using advanced single-cell technologies to study how individual tumor and immune cells change over time, and spatial tools to see how these cells interact within the tumor environment. A key focus will be on cancer-killing T cells. A tumor with more T cells at baseline or that has a greater influx of T cells during treatment may respond better, especially to the drug combination. Together, these studies will help identify biomarkers that can predict who benefits most from the therapy, paving the way for more personalized treatment strategies for advanced HR-positive, HER2-negative breast cancer.
Biography
Sara Tolaney, MD, MPH is the Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and is internationally recognized for her research and education leadership in breast cancer. She also serves as Associate Director of the Susan F. Smith Center for Women’s Cancers and is a Senior Physician at Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. Dr. Tolaney received her undergraduate degree from Princeton University and her medical degree from UC San Francisco. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in hematology and medical oncology at Dana-Farber Cancer Institute. She obtained her master’s in public health from Harvard School of Public Health.
Her research focuses on the development of novel therapies in the treatment of breast cancer and developing more effective and less toxic treatment approaches. Her work has demonstrated that a relatively low risk regimen is beneficial in women with early-stage node-negative HER2-positive cancers, and this works has been incorporated into national and international guidelines. She has developed several follow-up studies looking at novel approaches to early stage HER2-positive disease and has also played a significant role in development of CDK4/6 inhibitors, antibody drug conjugates, and immunotherapy in breast cancer. She currently chairs several registration studies in these areas and also leads many investigator-initiated trials. She is the author of over 150 peer-reviewed publications with manuscripts included in many prestigious journals such as the New England Journal, Lancet Oncology, Journal of Clinical Oncology, and JAMA Oncology.
