Norman Wolmark, MD

2012-2013 BCRF Project:
On behalf of National Surgical Adjuvant Breast and Bowel Project
Co-Investigators: Matthew J. Ellis, MD, PhD, Washington University School of Medicine, St. Louis, MO and Samuel A. Jacobs, MD, University of Pittsburgh Cancer Institute, Pittsburgh, PA

Technologies for unbiased discovery of the events underlying cancer are improving at a rapid pace. It is, therefore, critically important that scientists evolve their approaches to clinical investigation to match the demands and opportunities that the integrated studies of cancer DNA, RNA, and proteins - collectively referred to as "cancer 'omics" present.

The ready availability of tissue from patients receiving systemic treatment before surgery (neoadjuvant therapy) for breast cancer is of central importance to the 'omics field as serial sample acquisition can be reliably attempted before and after the initiation of therapy. Several National Cancer Institute Clinical Proteomic Tumor Analysis Consortium centers have, therefore, developed a collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the feasibility of conducting a deep proteogenomic analysis of samples from the phase II randomized clinical trial evaluating neoadjuvant chemotherapy regimens with weekly paclitaxel or eribulin followed by doxorubicin and cyclophosphamide in women with locally advanced HER2 negative breast cancer. The long-term objective of this study is to develop standard operating procedures that will allow integrated cancer 'omics from all neoadjuvant breast cancer protocols conducted by the NSABP, and indeed, by all cooperative groups.

Mid-year Progress: Mid-year Progress: This team has been busy completing pre-activation activities for their 50-patient pilot study, entitled, NSABP Discovery Protocol 1 ("DP-1"). To date, the contracting process has been completed and all the necessary agreements are in place. These agreements form the basis of the infrastructure necessary to support DP-1, including acollaboration between the NSABP, Washington University, and several National Cancer Institute U24 Clinical Proteomic Tumor Analysis Consortium (CPTAC) centers to determine the feasibility of conducting a deep proteogenomic analysis of samples from patients receiving neoadjuvant chemotherapy. Pre-study activities, which include clinical, regulatory, and logistical tasks, are 95% complete, and the group anticipates DP-1 being open to selected sites in early 2013. The ready availability of tissue from patients receiving systemic treatment before surgery for breast cancer is of central importance to the "omics" field as serial sample acquisition can be reliably attempted before and after the initiation of therapy. The long-term objective of this study is to develop standard operating procedures that will allow integrated cancer "omics" from all neoadjuvant breast cancer protocols conducted by the NSABP, and indeed, by all cooperative groups. By October 2013, Dr. Ellis's team plans to enroll and collect specimens from as many of the 50 patient sample size as possible.

BCRF funding has been also been applied towards a second NSABP study led by grantee Patricia A. Ganz, MD (University of California, Los Angeles). Clinical trials focus primarily on the efficacy of a treatment -- does it prolong survival or disease-free survival? The final outcomes and interpretation of clinical trials are often enhanced through collection of patient reported outcomes (PROs) related to symptoms and quality of life that reflect the experience of the patients receiving the therapy, especially when one treatment arm is expected to be substantially more toxic than the other.

A second kind of outcome study, less frequently included in this setting, is a cost of care study; however, such research is equally important for the interpretation of how best to implement the results of clinical trials in breast cancer once a trial has been completed. As new targeted therapies demonstrate benefit in advanced metastatic breast cancer, they are being moved into the adjuvant treatment of breast cancer. These new agents bring substantial promise for higher cure rates when added to standard adjuvant therapy but can also add substantially to the cost of care. The increased cost of care includes the drug itself, which may be considerable, along with additional costs that can be incurred due to increased toxicities resulting in additional office visits, prescribed medications to manage toxicities, as well as increased hospitalizations. Collecting this type of data prospectively, during the conduct of the trial, is essential in order to assess the additional cost burden of administering a new agent. BCRF funds are allowing researchers to collect data on the extra costs incurred by women who receive the new agent everolimus (Affinitor®) in addition to standard endocrine adjuvant therapy, in a large randomized trial, to determine whether or not the benefits of therapy outweigh the costs. BCRF support will help with the development of the questionnaire to collect the cost data as well as modest support for the additional data collection by the clinical trials staff. The team has started working on amending the study protocol and development of the data collection questionnaire.

Bio:
Norman Wolmark, MD is Chairman and Principal Investigator of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which is primarily funded by the National Cancer Institute and is based in Pittsburgh, Pennsylvania. He is also Professor and Chairman of Human Oncology, Drexel University School of Medicine.

Dr. Wolmark gained his MD at McGill University, Montreal, Canada and he subsequently completed his residency at the University of Pittsburgh. Dr. Wolmark was then appointed to the position of Cancer Expert at the Surgery Branch of the National Cancer Institute, Bethesda, Maryland. Dr. Wolmark is a member of numerous professional societies, including the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR), and the American Surgical Association (ASA).

He is a reviewer for the journal of Clinical Oncology and the New England Journal of Medicine and an editorial board member of the Journal of Women's Cancer, and Clinical Breast Cancer. He also serves on numerous boards and as an advisor to oncology programs, societies and institutes throughout the United States, Europe, and Asia.