Director

University of Pittsburgh Cancer Institute
Pittsburgh, PA

Nancy E. Davidson, M.D. is known for her seminal contributions as a physician-scientist to our understanding of the biology and treatment of breast cancer, the most common non-skin cancer in American women.  As a scientist she is recognized for discoveries in three areas. She was among the first to elucidate the role of apoptosis in the response of human breast cancer cells to estrogen deprivation and certain cytotoxic chemotherapies, both mainstays in the treatment of breast cancer in the clinic.  This work demonstrated that these two effective therapeutics are both anti-proliferative and pro-apoptotic.  Second, her team has demonstrated the feasibility of targeting the polyamine metabolic pathway in human breast cancer cells.  In particular the ability of certain analogues of native polyamines to inhibit proliferation, promote apoptosis, and down regulate expression of critical molecules like the estrogen receptor α  (ER) protein led to the phase II testing of one such analogue in women with metastatic breast cancer.  This research has truly spanned the bench to the bedside. Finally, her lab was the first to show that the ER gene (ESR1) is epigenetically regulated and that epigenetic silencing may account for the absence of ER protein expression in a fraction of human breast cancers, thereby rendering these tumors unresponsive to endocrine approaches.  Her team showed that human breast cancer cell lines that lack ER expression show methylation of the CpG island in the 5’ region of the gene as well as aberrant histone modification, leading to a transcriptionally inactive chromatin conformation. These changes can be reversed by exposure to DNA methyltransferase or histone deacetylase inhibitors, leading to expression of ER protein and sensitization to the growth inhibitory effects of tamoxifen.  These preclinical findings are now being validated in early phase trials in women with breast cancer.

Dr. Davidson has also made major contributions to our understanding about how to treat breast cancer.  An early and enduring focus has been on the management of premenopausal women with early stage breast cancer.  She was the leader of a major phase III trial of chemotherapy vs chemotherapy with ovarian suppression vs chemotherapy with ovarian suppression with tamoxifen for the management of premenopausal women with lymph node-positive steroid receptor-positive breast cancer.   This trial unequivocally demonstrated the impact of endocrine therapy in addition to chemotherapy in this setting and set the stage for the current international clinical trial of optimal endocrine therapy for premenopausal women. In addition she was a key organizer of a world-wide metaanalysis on the role of ovarian suppression for the management of steroid receptor-positive breast cancer in premenopausal women. She has been a major leader in two practice-changing studies that led to changes in the FDA label for two breast cancer drugs.  The JMA17 trial showed the additional benefit of an aromatase inhibitor, letrozole, after five years of tamoxifen for postmenopausal steroid receptor-positive breast cancer patients while the NSABP B31/N9831 analysis showed the advantage of trastuzumab, the monoclonal antibody directed against the HER-2 protein, when used in conjunction with chemotherapy for women with HER-2-overexpressing breast cancer.  She was the senior author on two studies that have informed our knowledge about how best to use the taxanes in early breast cancer; these suggest that weekly paclitaxel appears to give the best results with the least toxicity.  Finally she also served as the senior author for the pivotal trial that established a role for the anti-angiogenic agent, bevacizumab, in the treatment of metastatic beast cancer, leading to its FDA approval for this indication.

In summary Dr. Davidson has been an international leader in translational research in breast cancer.  She has been a pioneer in the area of epigenetic regulation of ESR1 in breast cancer, an area with broad clinical implications.  Finally, she has been a major leader in breast cancer clinical research, leading large collaborative efforts that have altered the standards of care for women with breast cancer.