Office Address:
2220 Pierce Avenue, Nashville, TN 37232

Professor of Medicine

Research Description

Dr. Mayer research endeavors have been focused on 1) the identification of targetable pathways in breast cancer, 2) ErbB signaling and endocrine therapy resistance in estrogen receptor positive (ER+) breast cancers, 3) PI3K signaling and endocrine therapy resistance in ER+ breast cancers, 4) chemotherapy resistance in triple negative breast cancers, and 5) biomarker prediction of treatment response in human breast cancers. Identification of targetable pathways in breast cancer. To enhance understanding of breast cancer biology and to elucidate molecular determinants of clinical efficacy, Dr. Mayer obtained a Vanderbilt Physician Scientist Development (VPSD) Award. The specific aims of this grant were to identify relevant tumor antigens by multidimensional liquid chromatography (LC) and tandem mass spectrometry (MS) using antibodies raised against specific peptide motifs recognized by circulating IgGs in breast cancer patients sera and to determine if these tumor antigens could be detected by immunohistochemistry in all different subsets of primary breast tumors. Preliminary results of this work led to testing of new therapeutic strategies targeting the phosphatidylinositol-3 kinase (PI3K)/Akt and correlated pathways in triple-negative, hormone-refractory and HER2-overexpressing refractory breast cancers, using biologically-based targeted agents. Initially, Dr. Mayer conducted a pilot project to determine the safety of an oral mTOR inhibitor in combination with an EGFR inhibitor in patients with metastatic breast cancer, addressing the synergism between EGFR and PI3K pathways. This study was partially funded by a Breast Cancer SPORE Pilot Project Grant. The outcome from this pilot project served as the preliminary data for her K23 Career Development Award. This grant included molecular analysis of individual breast cancers to determine how the biology of the cancer affects the response to the therapeutic agent. ErbB signaling and endocrine therapy resistance in ER+ breast cancers. Preclinical models and some clinical observations suggest that ER+ breast cancers initially inhibited by a selective estrogen-receptor modulator (SERM) can use autocrine ErbB signaling in order to escape SERM action. This mechanism involves crosstalk between growth factor signaling and ER. Dr. Mayer obtained a Breast Cancer Research Foundation American Association for Cancer Research (BCRF-AACR) Grant for Translational Breast Cancer Research to explore if clinically combining an aromatase inhibitor with an EGFR/HER2 inhibitor would restore sensitivity to endocrine treatment in ER+/HER2+ breast cancers and would prevent the emergence of cells resistant to endocrine therapy. As a continuation of this work, funds were also obtained through the Breast Cancer Specialized Program of Research Excellence (SPORE), Project 1 to determine 1) if combined neoadjuvant breast cancer therapy with the aromatase inhibitor letrozole and the HER2 tyrosine kinase inhibitor lapatinib induces pathologic complete responses in hormone receptor-positive breast cancers that overexpress HER2 and 2) to establish biomarkers predictive of response to this therapy, 3) to determine if the post-letrozole Ki67 in hormone receptor-positive/HER2-negative tumors mirrored the recurrence score as measured by RT-PCR of 21 selected genes in formalin-fixed tumor tissue sections, and 4) to use these biomarkers to discover gene expression signatures associated with response or resistance to estrogen deprivation. PI3K signaling and endocrine therapy resistance in ER+ breast cancers. Preclinical and a few clinical studies have already suggested that ER+/PI3K mutant tumors exhibit a lower response to antiestrogens compared to ER+/PI3K wild-type tumors. Upon recent renewal of the Breast Cancer Specialized Program of Research Excellence (SPORE), Project 1, Dr. Mayer is seeking to explore if the combination of antiestrogens with a PI3K inhibitor would be more effective against ER+/PI3K mutant

Research Keywords

Breast Cancer - Targeted Therapies

Education

MD - Federal University of Sao Paulo, Brazil (1993)
M.S.C.I. - Vanderbilt University School of Medicine, Nashville, TN (2006)
Postgraduate Training - University of Miami Health System, Miami, FL (1994)
Postgraduate/Graduate Training - Vanderbilt University School of Medicine, Nashville, TN (2006)