Joseph A. Sparano, MD

2012-2013 BCRF Project:
On behalf of Coalition of Cancer Cooperative Groups
Co-Investigators: Robert L. Comis, MD, Coalition of Cancer Cooperative Groups, Philadelphia, PA 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.

Bio:
Dr. Joseph Sparano is Professor of Medicine and Professor of Obstetrics, Gynecology, and Women's Health at the Albert Einstein College of Medicine, and Associate Chairman of the Department of Oncology at Montefiore Medical Center. He currently serves as the faculty supervisor of the Einstein Cancer Center Clinical Trials Office, and leads the Einstein Breast Cancer Working Group, a multidisciplinary group of physicians and scientists focused on translational breast cancer research. Other positions include Associate Chair for Disease Oriented Research in the Eastern Cooperative Oncology Group (ECOG), Vice Chair of the AIDS Malignancy Consortium (AMC), and Chair of the ECOG Breast Cancer Committee. He is a member of the several National Cancer Institute (NCI) scientific committees, including the Breast Cancer Steering Committee, and co-chair of the Breast Cancer Correlative Science Committee. He is principal investigator of a U10 grant funding Einstein as a main member institution of ECOG, and directs the New York Cancer Consortium (www.newyorkcancerconsortium.org ). He is a former director of the Hematology-Oncology Fellowship Program at Albert Einstein/Montefiore, and is the founder and program director for the ECOG Young Investigator Symposium; this meeting is held annually at the fall ECOG meeting since 2001, and is designed to introduce trainees and junior faculty members to cooperative group research. Dr. Sparano's area of expertise includes phase I-III clinical trials, developmental therapeutics, and clinical application of genomic profiling. He currently serves as the study chair of TAILORx (Trial Assigning Individualized Options for Treatment), the first NCI-sponsored trial integrating a gene expression assay in clinical decision making. He has authored or coauthored approximately 200 original articles, reviews, chapters, and editorials.