Titles and Affiliations
Co-Director of Breast Pathology
Professor of Pathology, Harvard Medical School
Research area
Discovering new strategies to treat estrogen receptor-positive breast cancer.
Impact
Estrogen receptor (ER)-positive breast cancer can be successfully treated with an anti-estrogen (endocrine) therapy in most cases, but resistance is common, and triple-negative breast cancer (TNBC) remains especially difficult to treat because it lacks the hormone-receptor and HER2 targets that guide most standard therapies. Dr. Sgroi is identifying predictors of treatment response across both of these breast cancer subtypes that can assist oncologists in the treatment-making process. The gene HOXB13 is expressed in some ER-positive breast cancers and is shown to be a predictor of response to endocrine treatments, and Dr. Sgroi has also shown that HOXB13 is expressed in TNBC and associated with poorer outcomes in these patients as well. However, the mechanism behind these observations is poorly understood. Dr. Sgroi is working to understand why HOXB13 predicts the benefit from extended endocrine therapy in women with ER-positive breast cancer and drives worse outcomes in TNBC, work that could open new avenues of treatment for both ER-positive breast resistant to anti-estrogen therapy and for TNBC more broadly.
Progress Thus Far
Dr. Sgroi and his team have made several key insights into the role of HOXB13 in the tumor immune microenvironment (TIME). Analysis of gene expression and proteomic data from The Cancer Genome Atlas revealed that HOXB13-expressing tumors are associated with activation of pathways that may shape the tumor immune microenvironment directly. The team found that HOXB13-induced pathway activation creates an immunosuppressive TIME in both ER-positive and TNBC models. This past year, the team found that this pro-tumorigenic effect is eliminated by ovariectomy and requires the presence of estrogen and progesterone to occur, a finding consistent with separate research showing that ovariectomy significantly improves survival outcomes in women with TNBC and ER-negative breast cancer.
What’s next
In the upcoming year, Dr. Sgroi and his team will validate their HOXB13 findings in two additional models of TNBC and will analyze a cohort of ER-positive breast cancer patients using spatial protein imaging technology to determine whether human ER-positive, HOXB13-expressing tumors also possess this same immunosuppressive microenvironment. Together, this work aims to lay the groundwork for new regimens pairing anti-hormonal agents with immunotherapy tailored to ER-positive and TNBC patients whose tumors express HOXB13.
Biography
Dennis C. Sgroi, MD is a Professor of Pathology, Harvard Medical School, and Co-Director of Breast Pathology and Member of the Center for Cancer Research at Massachusetts General Hospital. He maintains an active clinical practice on the breast pathology consultation service, and he is actively engaged in translational research. He has served on the scientific advisory board for the Barnett Institute at Northeastern University and currently serves on the scientific advisory board for the Ontario Institute for Cancer Research.
The overarching goals of research in the Sgroi laboratory are to develop better ways to identify patients who are at risk for the development of breast cancer and to identify those breast cancer patients who are likely to benefit from targeted drug therapies. His laboratory is taking several different approaches to achieving these goals. First, they are deciphering specific molecular events that occur during the earliest stages of tumor development and using this knowledge to develop biomarkers that will predict for increased risk of progression to cancer. Second, using advance molecular technologies, they are searching for novel breast cancer biomarkers to identify patients with hormone-receptor-positive breast cancer who are most likely to benefit from extended hormonal therapy and from novel targeted therapeutics.
