Director of the Lester and Sue Smith Breast Center
Professor of Medicine and
Cellular and Molecular Biology
Baylor College of Medicine
Adjuvant breast cancer therapy is given after removal of the primary tumor to kill cancer cells that have disseminated to other parts of the body and would otherwise persist and grow, ultimately resulting in metastasis. A laboratory test that could identify whether disseminated cells are present after adjuvant therapy would help doctors manage treatment of a patient’s breast cancer. If a standard drug is not working, a different drug could be offered while the disease is still curative, before the development of overt metastatic disease. If disseminated cells are not present then surgery is adequate and systemic adjuvant therapy could be avoided. A new technique has recently been developed that has the potential to track disseminated disease in a very specific way. Tumors develop because of the accumulation of changes in the genome called “somatic mutations”. Somatic mutations occur during the course of tumorigenesis – acquired mutations that in some way benefit the tumor. They are only present in the tumor cells, not in normal cells. Remarkably somatic mutations can be now detected in the blood using new very sensitive technologies called circulating tumor(ct) DNA assays. In the coming year, Dr. Ellis and colleagues will collect serial samples from patients enrolled in an adjuvant chemotherapy trial and sequence the patients’ tumor DNA. They will develop a ctDNA assay to track disseminated tumor cells to determine the effectiveness of the treatment in eradicating the disseminated cells. If successful, the ctDNA assay could become a powerful clinical tool in personalized medicine by assessing treatment effectiveness early in the course of therapy so that changes in therapy can be considered while the cancer is still curable.
BCRF has provided critical support for National Cancer Institute-sponsored Cooperative Group neoadjuvant trials in women with ER+ breast cancers. One such trial is the ALTERNATE trial, led by Drs. Ma and Ellis under the auspices of the Alliance for Clinical Trials in Oncology, one of the NCI cooperative groups. The overarching objective of this Phase III neoadjuvant treatment trial is to validate a test called modified Preoperative Endocrine Prognostic Index (PEPI) in predicting endocrine therapy sensitivity and to develop a mutation based classification of ER+ breast cancer that will inform new approaches to reduce the recurrence rate.
Dr. Ellis is also the lead investigator on a study to develop and test experimental models of metastatic breast cancer called patient derived xenografts or PDX. This project, which is part of the Evelyn H. Lauder Founder’s Fund AURORA US effort, brings together a team of investigators with strong track records of investigating breast cancer biology and therapeutics using models generated directly from patients with breast cancer. Through the generous support of the BCRF Founder’s Fund, the four funded centers (Baylor College of Medicine, Houston, TX, Washington University, St. Louis, MO, Memorial Sloan Kettering Cancer Center, New York, NY and Univeristy of Utah, Huntsman Cancer Institute, Salt Lake City, UT) are developing new PDX models designed to study the metastatic process by preparing PDX of both the primary tumor and one from a metastatic site. The investigators will use these models to pinpoint the mechanisms whereby tumors spread from the breast to cause a lethal systemic disease. The study will also generate a resource for investigators who want access to PDX for therapeutic and biological studies. In their first year of BCRF support, the consortium has generated one primary metastatic PDX pair and are actively screening high-risk patient populations. Together with ongoing projects, they now have nearly 100 PDX models and are organizing the clinical and genomic data for access by BCRF investigators.
Originally from the United Kingdom, Matthew Ellis completed his medical training in the U.K. at the Universities of Cambridge and London. After 11 years at Washington University in St Louis, Dr Ellis is the incoming Director of the Lester and Sue Smith Breast Center and Professor of Medicine and Cellular and Molecular Biology at Baylor College of Medicine, Houston Texas. His research interests include the identification of genes that affect responses and resistance to endocrine therapy in breast cancer Patients. Dr. Ellis is also co-principal investigator for the NCI-funded Proteome Characterization Center and co-project leader for The Cancer Genome Atlas (TCGA) Breast Project. Dr. Ellis was the recipient of ASCO's 2015 Gianni Bonadonna Breast Cancer Award and Lecture for his pioneering research into the clinical relevance of activating mutations in HER2 and in the deployment of patient-derived xenografts for the pharmacological annotation of breast cancer genomes.