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. At the trial’s primary analysis, the combination of sacituzumab govitecan and pembrolizumab did not significantly improve progression-free survival compared to sacituzumab govitecan alone. However, analyses of genome sequence, gene expression, and protein expression in tumor samples collected before and during treatment, identified specific genetic mutations and gene expression patterns associated with better or worse progression-free survival on each treatment arm, offering an important first step toward understanding which patients are most likely to benefit from each approach.
What’s next
Next, Dr. Tolaney and her team will evaluate the immune cells within tumors in greater detail, assessing for DNA damage and activation of the cGAS/STING pathway, a key immune-signaling route triggered by DNA damage, within tumor cells. The team will determine the number, location, and functional state of different immune cell types within the tumor, including cancer-killing T cells as well as other immune cells that may instead help the cancer grow. The team plans to map exactly where specific gene expression signatures are located within tumor and immune regions of the tissue. By integrating all of these data, they aim to determine whether the presence of specific immune cell types within a tumor can predict response to sacituzumab govitecan with pembrolizumab, helping identify which patients are most likely to benefit from this combination and informing the development of more effective treatments for endocrine-resistant HR-positive, HER2-negative metastatic 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.
