Robert L. Comis, MD

2012-2013 BCRF Projects:
1) On behalf of Coalition of Cancer Cooperative Groups
Co-Investigators: Joseph A. Sparano, MD, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY and Kathy D. Miller, MD, Indiananopolis University School of Medicine, Indianapolis, IN

National Cancer Institute (NCI) statistics as of January 2009 reveal that there were over 2.7 million women alive in the United States, who have a history of cancer of breast cancer. Approximately 30% of these women already have, or will eventually develop recurrence and incurable metastatic disease. Late relapse, which is defined as occurring five or more years after an initial diagnosis of operable breast cancer, accounts for up to one-half of all breast cancer recurrences. It is difficult for researchers to study tumor and host-associated factors driving late recurrence because of the lack of adequate biospecimens (i.e. primary and metastatic tumor specimens, blood specimens, and germline DNA) linked to clinical data with sufficiently long follow-up. Further complicating this issue, late recurrence may be driven by dynamic rather than static host factors that may wax or wane with time and thus require serial biospecimen collection at diagnosis, before recurrence, and at recurrence, rather than the usual paradigm of collecting biospecimens only at diagnosis.

Although late relapse has been recognized as a major clinical problem, accounting for up to one-half of all relapses in estrogen receptor positive (ER+) disease, it also may occur unpredictably in other breast cancer subtypes. For example, when evaluating patterns of recurrence in 4,950 eligible patients enrolled in the E1199 trial who received adjuvant chemotherapy (plus endocrine therapy if ER+), the annual hazard rate (HR) of recurrence within the first five years of diagnosis was about three-fold higher for patients with triple negative breast cancer (TNBC), and two-fold higher for HER2 positive (HER2+) breast cancer (before the use of adjuvant trastuzumab or Herceptin®), compared with ER+ and/or progesterone positive, HER2-negative disease, but was higher for ER+/PR+ disease compared with other subtypes beyond five years, In addition, recurrence risk persisted over time for all subtypes after five years. Moreover, host factors such as body mass index (BMI) at diagnosis may contribute to late relapse, especially in ER+/PR+ disease. Two prior reports have found a similar association between obesity and recurrence specifically in ER-positive disease, but this study indicates that obesity is specifically associated with late recurrence.

There are no clinical or pathologic features predictive of late relapse; gene expression assays predict earlier recurrences. Although extended adjuvant therapy with an aromatase inhibitor given for up to five years after two to five year course of tamoxifen therapy has been shown to reduce the risk of recurrence in ER-positive disease, the absolute benefits are low, resulting in many patients receiving unnecessary therapy. The overall aims of this multi-institutional, multi-year trial, therefore, are to: (1) create a plasma/serum biorepository for evaluating determinants of late relapse; (2) create a biorepository of metastatic tumor samples in patients who have had a late relapse; (3) determine body mass index (BMI) and co-morbidity burden in patients with operable breast cancer 5 or more years after diagnosis, and (4) determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence.

Mid-year Progress: The Coalition of Cancer Cooperative Groups reports that the establishment of a Late Relapse Biorepository is proceeding as scheduled. Presently, the protocols for the TAILORx and E5103 studies, which form the basis for this endeavor, have been modified to allow patients participating in the original studies to enroll in this new research study if eligibility requirements are met. Recruitment efforts will commence in March 2013, immediately following February activation of the amended protocols. All processes and procedures are in place.

2) On behalf of Eastern Cooperative Oncology Group

The Breast Committee of the Eastern Cooperative Oncology Group (ECOG) continues to perform correlative laboratory studies attached to cutting-edge clinical trials and research studies utilizing specimens obtained and stored from patients participating in ECOG trials. Current active trials seek to determine is there is a link between a woman's ability to metabolize tamoxifen and her progression-free survival from metastatic breast cancer (E3108) and to determine whether, after systemic therapy for metastatic disease, immediate removal of the primary tumor confers survival benefit more than the current practice of waiting to do the surgery (E2108). Additionally, specimens archived from older ECOG trials continue to provide resources for current research necessary to expand the understanding of the causes and treatment of breast cancer.

Mid-year Progress: Over the last year, several projects have requested the use of archived specimens, two of which resulted in published manuscripts in 2012. Current active trials continue, one of which seeks to determine if there is a link between a woman's ability to metabolize tamoxifen and her progression-free survival from metastatic breast cancer (E3108). Another aims to determine whether, after systemic therapy for metastatic disease, immediate removal of the primary tumor confers survival benefit more than the current practice of waiting to do the surgery (E2108). A third study is trying to identify markers that would predict aromatase-inhibitor musculoskeletal symptoms (AIMSS) which lead to discontinuation of adjuvant therapy with AIs in 30% of treated patients (E1Z11). Presently, projects continue to explore markers associated with taxane neuropathy, treatment response, and establishment of predictive and prognostic biomarker profiles. Active procurement of outstanding materials is also pursued. Additionally, for all trials, procurement will be ongoing to replace exhausted resources.

Bio:
Dr. Robert L. Comis, President and Chairman of the Coalition of Cancer Cooperative Groups, is Group Chair of the Eastern Cooperative Oncology Group (ECOG), and Professor of Medicine and Director of the Drexel University Clinical Trials Research Center in Philadelphia, PA.

A leader in international clinical trials research since 1977, Dr. Comis is a champion for patient access to cancer clinical trials, spearheading multiple initiatives to raise awareness about the pivotal role of cancer clinical trials in cancer prevention, detection and treatment. Dr. Comis is a member, Board of Directors, of C-Change and the National Coalition for Cancer Research. He has served on the editorial boards of the Journal of Clinical Oncology, Cancer Research, and Clinical Cancer Research. His previous board positions include the American Radium Society and the American Society of Clinical Oncology, where he served the society in a variety of other capacities including the Executive Committee, Chair of the Program, Nominating and Audit committees, and Steering Committee for the Clinical Trials Workshop.