Matthew J. Ellis, MD, PhD

1) On behalf of Cancer & Leukemia Group B
(made possible by generous support from Genentech)
Co-Invesigators: Richard L. Schilsky, MD, Chairman, Cancer and Leukemia Group B, Chicago; Lisa A. Carey, MD, University of North Carolina at Chapel Hill; and William M. Sikov, MD, Brown University, Providence, RI

Advances in the postoperative treatment of breast cancer have led to new challenges in drug development. Recurrence rates from breast cancer have declined substantially in recent years. While there is no question that the decline in recurrence is good news, it has lead to an increasing need to conduct very large clinical trials in order to detect small benefits from new treatments. In addition, it often takes years before results are available. The preoperative administration of systemic therapy (e.g., chemotherapy, hormonal therapy, and/or targeted therapy) is safe and effective. In addition, from a research standpoint, it has two major benefits: 1) researchers can quickly see whether treatment shrinks the cancer and 2) samples of the cancer can be obtained for study before and after treatment to assess the impact of therapies.

Over the next year in the CALGB, researchers are going to test two new targeted therapies using this approach. In patients with tumors that are dependent on HER2, they will compare trastuzumab (Herceptin®) versus lapatinib (Tykerb„µ) versus both. In patients with hormone receptor-poor/HER2-negative tumors (often referred to as triple negative or basal-like), they will test the addition of an antibody that shuts off new blood vessel formation, bevacizumab (Avastin®). These studies represent a unique opportunity for the CALGB as researchers will have the ability to see the effects of their treatments on tumors before surgery and will be able to gather extensive tissues for later study.

With support from BCRF, they will build and maintain the infrastructure needed to collect these tissues, to store them until the clinical studies are completed, to distribute them to collaborating investigators, and to perform studies on them. The results of this program should improve our understanding of how our available therapeutics kill cancer and lead to improved treatment approaches.

2) On behalf of the American College of Surgeons Oncology Group
Co-Investigators: Karla Ballman, PhD,, Mayo Clinic, Rochester, MN; Kelly K. Hunt, MD, University of Texas MD Anderson Cancer Center, Houston, TX; and John A. Olson, Jr., MD, PhD, Duke University, Durham, NC

Postmenopausal women with strongly ER-positive stage 2 and 3 breast cancer who are at risk for a mastectomy are candidates for preoperative endocrine therapy to down stage the tumor and improve surgical outcomes. This practice is supported by randomized clinical trials that show an increased chance of breast conservation when aromatase inhibitors were utilized in this indication in comparison with tamoxifen.

In this project, the ACOSOG researchers are using tumor samples from ongoing ACOSOG clinical trial Z1031 to address why estrogen receptor positive breast cancers are not universally responsive to this approach. Specifically, they are asking if large gains in DNA segments in tumor cells called "amplicons" are associated with treatment resistance. This information will not only define which patients are suitable for preoperative endocrine therapy, but will aid in the identification of genes that are responsible for treatment failure.

This may lead to the development of new treatments that increase the effectiveness of endocrine therapy through the application of targeted pharmacological agents. The monthly accrual rate is on target and the trial is estimated to close in summer 2009. The trial continues to provide the availability of pre and post endocrine treatment tissue samples that will allow valuable new insights into the biological basis for the success and failure of endocrine therapy.

Bio:
Originally from the United Kingdom, Matthew Ellis completed his initial medical training in the U.K. at the Universities of Cambridge and London before coming to the United States in 1991 as a Medical Research Council of Great Britain Traveling Fellow at the Lombardi Cancer Research Center at Georgetown University. He stayed at Georgetown until 2000, at which time he was Assistant Professor of Medicine in the Division of Hematology/Oncology.

In 2000, he became Director of the Duke University Breast Cancer Program and Associate Professor in the Department of Medicine. After 3 years with Duke University, Dr. Ellis took over as the Head of Medical Oncology at Washington University in St. Louis where he is currently a Tenured Associate Professor of Medicine and Director of the Breast Cancer Program at Siteman Cancer Center.

Dr. Ellis's research has focused on the use of aromatase inhibitors and targeted therapy in treating breast cancer. He is a member of the Cancer and Leukemia Group B (CALGB) Breast Cancer Committee and Chairman of the Working Group for Correlative Science in Breast Cancer.