Andrea Richardson, MD, PhD

In the past year, investigators at the Brigham and Women's Hospital and Dana-Farber Cancer Institute have demonstrated that tumor expression levels of two 8q22 amplified genes were highly predictive of resistance to anthracycline chemotherapy in a recently completed neoadjuvant trial of epirubicin monotherapy in ER-negative breast cancers, but were not predictive of response to cisplatin chemotherapy. In vitro experiments show that the effects of these genes on drug resistance may be mediated in part through suppression of tumor cell death (apoptosis) and autophagy. In another avenue of work, the researchers found that degree of chromosomal instability in triple-negative breast tumors as measured by number of chromosomal breakpoints is highly associated with sensitivity to the DNA-damaging agent, cisplatin. Their findings this year on prediction of response to anthracyclines or cisplatin chemotherapies suggest a possible future approach to selection of optimal therapy for personalized treatment of breast cancer.

This year, in collaboration with investigators at MIT/Whitehead Institute, the Dana Farber/Brigham & Women's researchers identified an important and here-to-fore unrecognized metastasis-promoting alteration in certain human breast cancers. This alteration is the loss of microRNA-31, a metastasis suppressor. MicroRNAs do not code for proteins themselves, but are master regulators of the expression of panels of genes, thereby controlling key biological processes. In basic science work done by Dr. Robert Weinberg (also supported by BCRF), it was determined that miR31 is a microRNA that controls genes involved in cell invasion, adhesion, and survival. When miR31-control is lost, the tumor cell gains the ability to survive and metastasize to distant sites.

This will be the first translation of that basic work into the clinical realm and the observations made will be quite novel. In a pilot study, the group at Dana-Farber found that loss of miR31 in primary breast tumors was highly associated with metastatic recurrence, independent of other prognostic factors such as tumor grade or subtype. In this application, the group will validate miR31 as a predictor of metastatic recurrence in a larger cohort of primary breast cancers and will also investigate whether miR31 expression changes/decreases as tumors progress from growing in the breast to growing in distant sites. In related work, the Dana-Farber team will investigate the role of microRNAs in controlling genetic instability and response to chemotherapy in triple negative breast cancer.

Bio:
Andrea Richardson is an Assistant Professor of Pathology at Harvard Medical School. She received her MD and PhD degrees in 1991 from University of Texas Southwestern Medical and Graduate Schools. Her graduate work in Dallas involved the molecular analysis of chromosomal translocations associated with childhood leukemia. From there, she moved to Boston for a residency in anatomic pathology at Brigham and Women's Hospital. She stayed on to complete subspecialty training in breast pathology and cytopathology. After three years in private practice as a breast pathology specialist, Dr. Richardson was recruited back to Brigham and Women's Hospital and Dana Farber Cancer Institute in 2000 to establish and serve as director of the DF/BWH Breast Tissue Bank for the Harvard SPORE in breast cancer.

She maintains both an active clinical practice on the BWH breast pathology consultation service and a translational research laboratory at DFCI. Her research is focused on developing a better understanding of breast cancer heterogeneity though microarray and pathologic profiling of human breast tumors. The goal of this work is to develop a comprehensive molecular understanding of breast cancer pathobiology so as to more effectively diagnose and treat breast cancer patients.

Recently, her lab has focused on developing predictors of response to DNA damaging agents in triple negative breast cancer, and on study of a newly recognized amplification on chromosome 8q22 and its role in chemotherapy resistance. In collaborations with Dr. Weinberg, Dr. Richardson has explored how tumor-stromal interaction, mesenchymal stem cells and microRNAs contribute to the process of metastasis and poor outcome in breast cancer patients. Her future work will further evaluate the role of microRNAs in chromosomal instability in triple negative breast cancers and will develop microRNAs as predictors of outcome in patients.