The research focus of Matthew P. Goetz, M.D., is on estrogen receptor positive breast cancer and the development of novel therapeutics for endocrine-resistant breast cancer. His laboratory and clinical work is funded by the National Institutes of Health.
- Pharmacogenetics of tamoxifen. A notable area of Dr. Goetz's focus has been the pharmacogenetics of tamoxifen. Out of this work, and in collaboration with the Developmental Therapeutics Program of the National Cancer Institute (NCI), Dr. Goetz has led a team of investigators in the development of a novel formulation of endoxifen hydrochloride for the treatment of estrogen receptor positive breast cancer. The first-in-human phase I studies of endoxifen hydrochloride started in 2011 at Mayo Clinic and the NCI, and a phase II study of endoxifen began in 2014 within the Alliance for Clinical Trials in Oncology, with the initial focus being in AI refractory, metastatic breast cancer.
- Breast Cancer Genome-Guided Therapy (BEAUTY) study. Dr. Goetz co-leads with Judy C. Boughey, M.D., the BEAUTY study, which is funded by the Mayo Clinic Center for Individualized Medicine and the Mayo Clinic Cancer Center. The goal of this study is to identify novel genetic alterations and changes in cancer pathways both at the time of diagnosis and after completion of neoadjuvant chemotherapy in women with high-risk breast cancer. In this study, both the host and tumor genomes are sequenced prior to therapy, after 12 weeks of paclitaxel and at the time of surgery.
Significance to patient care
Tamoxifen has been the most important drug for the treatment and prevention of premenopausal and postmenopausal breast cancer. Many studies have demonstrated that low endoxifen concentrations in patients with genetic and drug-induced reductions in the CYP2D6 enzyme are associated with higher rates of breast cancer recurrence. Because liver metabolism limits the concentrations of endoxifen that can be achieved, the direct delivery of endoxifen will allow for achievement of much higher endoxifen concentrations than is currently possible when tamoxifen is delivered using a standard dose.
A critical element of the BEAUTY study is the development of patient-derived xenografts in which patients' tumor tissue is kept alive by implanting tumor cells into immune-compromised mice before and after chemotherapy. The use of these mouse avatars will allow Dr. Goetz and his colleagues to quickly determine whether the genetic alterations identified by sequencing are functional, with the initial focus on studying novel drugs and drug combinations in avatars derived from women with chemotherapy resistance. The laboratory studies for BEAUTY are being led by Liewei Wang, M.D., Ph.D., and Richard Weinshilboum, M.D., who co-lead the Mayo Clinic Pharmacogenomics Research Network.
- Co-principal investigator, Mayo Clinic Breast Cancer Specialized Program of Research Excellence (SPORE), 2014-present
- Co-leader, Women's Cancer Program, Mayo Clinic Cancer Center, 2014-present
- Chair, Breast Cancer Disease-Oriented Group, Mayo Clinic Cancer, 2012-present