Massachusetts General Hospital Boston, Massachusetts
Co-Director of Breast Pathology Professor of Pathology, Harvard Medical School
Discovering new strategies to treat estrogen receptor-positive breast cancer.
Estrogen receptor (ER)-positive breast cancer can be successfully treated with an anti-estrogen (endocrine) therapy in most cases, but resistance is common. Dr. Sgroi is identifying predictors of treatment response in ER-positive breast cancers 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, but the mechanism 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, which will provide new avenues of treatment for ER-positive breast cancers that are resistant to anti-estrogen therapy.
Dr. Sgroi and his team have made several key insights into the role of HOXB13 in the tumor immune microenvironment (TIME). The team performed a small pilot study analyzing interactions among tumor cells and their environment to assess whether the TIME in their HOXB13-expressing triple-negative breast cancer (TNBC) model represents the TIME in human TNBCs expressing HOXB13. In their pilot study of four TNBC samples, they observed that HOXB13-expressing tumors have fewer activated T cells and more exhausted T cells compared to tumors that do not have HOXB13. The results from this pilot are consistent with their findings from the TNBC model, and the team plans to interrogate a larger cohort of human TNBCs.
In the upcoming year, Dr. Sgroi and his team will test the growth inhibiting effect of combining anti-hormonal therapy with immunotherapy in their TNBC model. In addition, they will expand upon their preliminary findings that HOXB13 expression is associated with an immune-suppressed microenvironment in TNBC.
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.
2015
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