The research focus of Matthew P. Goetz, M.D., is on estrogen receptor (ER) positive breast cancer and the development of novel therapeutics for endocrine-resistant breast cancer. His laboratory and clinical work is funded by National Institutes of Health grants, including R01 CA 133049-3 and P50 CA 116201-6 (Mayo Clinic Breast Cancer SPORE).
- 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 NCI/DTP, he has led a team of investigators in the development of a novel formulation of endoxifen (endoxifen hydrochloride) for the treatment of ER positive breast cancer. Initial preclinical toxicology and pharmacology studies (in the laboratories of Matthew M. Ames, Ph.D., and Joel M. Reid, Ph.D.) were completed in 2010, and first-in-human phase I studies of endoxifen hydrochloride commenced in 2011 at Mayo Clinic (NCT01327781) and NCI (NCT01273168). A phase II study of endoxifen will commence in 2013 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 — tamoxifen has been the most important drug for the treatment and prevention of premenopausal and postmenopausal breast cancer. Many studies indicate that endoxifen concentrations are low in patients with genetic and drug-induced reductions in CYP2D6. 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.
BEAUTY — a critical element of this 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.
- Deputy Director, Mayo Clinic Breast Cancer SPORE (Principal Investigator: James N. Ingle, M.D.)
- Chair, Breast Cancer Disease-Oriented Group, Mayo Clinic Cancer Center