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Dennis C. Sgroi, MD
Co-Director of Breast Pathology
Massachusetts General Hospital
Professor of Pathology, Harvard Medical School
- Seeking new strategies to prevent resistance to hormonal therapies.
- Laboratory studies are ongoing to identify biomarkers to guide treatment of hormone-positive breast cancer.
- Successful targeting of these genetic events with existing drugs could have a near-term impact in overcoming resistance to hormonal therapies and improving outcomes in patients with early stage hormone positive breast cancer.
Five years of hormonal therapy, such as tamoxifen or an aromatase inhibitor, has been shown to dramatically reduce the risk of recurrence of hormone-positive breast cancer. For some women, extended hormone therapy may be necessary to further reduce risk of recurrence. Dr. Sgoi has identified a biomarker that may identify those women at increased risk of recurrence for whom extended hormone therapy may be recommended.
Full Research Summary
Hormone receptor (HR)-positive breast cancer accounts for the majority of all breast cancers diagnosed worldwide. Anti-estrogen therapy (a.k.a. hormonal therapy) has been shown to dramatically reduce the risk of recurrence in hormone receptor (HR)-positive breast cancers, but late recurrence (five years or more after treatment) remains a clinical challenge.
A critical unmet need is to identify and validate a biomarker that can reliably identify women with early-stage, HR-positive breast cancer with a high risk of recurrence. For these women, extended adjuvant hormonal therapy may be recommended.
Dr. Sgroi developed a breast cancer index (BCI) assay to predict which patients will benefit from extended hormone therapy. A key component of the assay is the expression ratio of two genes: HOXB13 and IL17RB. His team recently demonstrated that the HOXB13/IL17RB gene expression biomarker uniquely predicts benefit from extended adjuvant hormone therapy.
Specifically, those patients with HR-positive breast cancers whose tumor have high HOXB13 and low IL17RB benefited from extended adjuvant hormone therapy. Conversely, those whose tumor had low HOXB13 and high IL17RB had worse outcomes in spite of extended therapy, suggesting that IL17RB may be a target to prevent resistance to hormone therapy.
This year, the team is working to understand how HOXB13 and IL17RB interact to affect sensitivity to hormone therapy. For those patients whose tumor expresses low levels of HOXB13 and high levels of IL17RB, successful completion of this project would provide strong support for targeting IL17RB to overcome drug resistance.
Dr. Dennis C. Sgroi 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. 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. He is currently on the scientific advisory board for the Ontario Institute for Cancer Research, and has served on the scientific advisory board the Barnett Institute at Northeastern University.