Dennis C. Sgroi, MD
Director of Breast Pathology
Massachusetts General Hospital
Associate Professor of Pathology
Harvard Medical School
Human Breast Cancer Anti-Hormonal Resistance
My laboratory is currently focused on applying high-throughput DNA microarray and proteomic technologies as a means to predict the clinical behavior of human breast cancer in the setting of specific hormonal and chemotherapeutic regimens. Recently, we have independently developed two complementary biomarkers, the HOXB13/IL17BR (H/I) index and the molecular Grade Index (MGI) that predict endocrine responsiveness (to both tamoxifen and letrazole) and risk of recurrence, respectively, in early stage ER+ breast cancer.
This novel biomarker outperforms existing biomarkers in predicting outcome, and comparative analysis to assess the clinical significance of this biomarker is currently underway in several prospective clinical trials. Given that HOXB13 expression in clinical breast cancers is associated with lack of endocrine-therapy responsiveness and poor clinical outcome, we are currently investigating the functional activity of HOXB13.
Notably, we have demonstrated that HOXB13 is regulated by estrogen and serves as a surrogate marker for a dysfunctional estrogen receptor signaling pathway. Furthermore, we have demonstrated that ectopic expression of HOXB13 promotes tumor growth and confers tamoxifen resistance in both ovarian and breast cancer cells lines. We are actively investigating the molecular mechanisms by which HOXB13 confers resistance to tamoxifen, and exploring the possibility that HOXB13 confers resistance to aromatase inhibitors.
Dennis Sgroi, MD
* Sonka Dahiya
* Jeong-Eun Lee
* Zuncai Wang
* Erin Carney
* Heather Provencher
In collaboration with Dr. Barry Karger of the Barnett Institute, we are currently using advanced tandem mass spectrometry bioanalytical technologies to discover protein biomarkers that are indicative for increase breast cancer risk in women with benign breast disease.
In addition, our laboratory, in collaboration with multiple investigators from the NCI as well as MD Anderson Cancer Center, is performing gene expression analysis of HER2-overexpressing breast cancer brain metastases as a means to identify novel molecular pathways associated with brain metastases.
Lastly, our laboratory is using novel artificial transcription factor technologies to understand the molecular mechanisms associated with drug-resistance in human breast cancer.