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Otto Metzger, MD
Instructor in Medicine
Dana-Farber Cancer Institute
Conquer Cancer, the ASCO Foundation
Goal: To improve treatment responses for patients diagnosed with invasive lobular carcinoma (ILC).
Impact: Dr. Metzger and his colleagues have designed a clinical trial and are conducting laboratory-based studies that will inform strategies to prevent breast cancer recurrence in patients diagnosed with invasive lobular carcinoma (ILC). The identification of key mechanisms involved in resistance to standard-of-care treatments could lead to improved diagnostic and therapeutic approaches that will improve outcomes for ILC patients.
What’s next: Dr. Metzger’s team is searching for molecules responsible for some ILC tumors’ failure to respond to either drugs that target the cancer cells’ dependence on hormones (tamoxifen), or drugs that target signals regulating cell division (palbociclib).
ILC accounts for 10 percent of all breast cancers and are usually estrogen receptor positive. The ILC subgroup of breast cancer patients typically receive anti-estrogen therapy, but ILC patients relapse more frequently and the reason why is unknown. Dr. Metzger is therefore conducting both clinical and laboratory-based experiments that will inform future treatment strategies, and possibly overcome mechanisms that drive recurrence in patients with ILC.
Full Research Summary
Research area: Investigating mechanisms of resistance to endocrine therapy in patients with invasive lobular carcinoma (ILC).
Impact: There are several treatment options for patients with estrogen receptor (ER)-positive breast cancer. The recently approved CDK4/6 inhibitors, such as palbociclib, and endocrine therapies such as tamoxifen, have been successful in patients with early stage or advanced ER-positive breast cancer. ILC is a clinically and pathologically distinct form of ER-positive breast cancer but is treated as other ER-positive breast cancers without a clear understanding of the best treatment for these patients. As a result, ILC patients have a higher rate of recurrence than is seen with other ER-positive breast cancers. Dr. Metzger’s Conquer Cancer Foundation project, supported by BCRF, is focused on improving treatment strategies to prevent relapse in ILC patients.
Current research: Dr. Metzger is conducting a small preoperative clinical trial coupled to laboratory studies to identify key regulators of treatment resistance in patients with ILC.
What he’s learned so far: In early results, he found that tumor samples from patients with ILC had a distinct pattern of estrogen signaling not seen in IDC. These observed differences may explain why ILC patients relapse more often.
What’s next: In the coming year, his team will examine the response to CDK4/6 inhibitors in ILC versus IDC patients.
Otto Metzger received his MD from Federal University of Minas Gerais in his native Brazil. He then completed an internal medicine residency in a top-ranked general hospital, Hospital Felicio Rocho, and a medical oncology fellowship at the Brazilian National Cancer Institute (INCA). Motivated to be more involved in research, he joined a research fellowship program at the Institute Jules Bordet in Belgium. While in Brussels he conducted a series of translational research investigations focused on understanding the molecular underpinnings of lobular tumors. He identified a subpopulation of lobular tumors classified as high-risk using the Genomic Grade Index gene signature.
Upon completing his research fellowship in Brussels, Otto Metzger moved to Dana-Farber Cancer Institute as a Breast Cancer Goldfarb Fellow. In Boston, in conjunction with his clinical duties, he continued his research projects involving lobular breast cancer. In collaboration with the Breast International Group and using data from the HERA trial, he demonstrated that patients diagnosed with lobular tumors classified as HER2-positive derive the same magnitude of benefit from adjuvant trastuzumab when compared to HER2-positive ductal carcinoma. Subsequently, in collaboration with the International Breast Cancer Study Group, he performed an analysis using data from the phase III study BIG 1-98. His results points to a tamoxifen-resistant phenotype among patients diagnosed with lobular carcinoma.
In addition to his work as a physician at Dana-Farber, Otto Metzger holds an executive officer position at the Alliance for Clinical Trials in Oncology where he oversees the scientific and operational aspects of national and international clinical trials dedicated to breast cancer. Otto Metzger is also actively involved in teaching and advancing education efforts both within DFCI and abroad
BCRF Investigator Since