Julie R. Gralow, MD

1) On behalf of the Southwest Oncology Group
(made possible by generous support from Play For P.I.N.K.)
Co-Investigator: Peggy I. Porter, MD, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle

Sixty percent of all U.S. cancer patients are 65 years of age or older, and this number is expected to rise considerably in the next decade. There are many reasons why older patients may respond to cancer treatments differently than younger patients, including increasing numbers of general health problems, medications, and other age-related changes. Determining how best to treat older cancer patients, and determining the risks and benefits of cancer therapies in this population, is becoming increasingly critical. Approved cancer therapies are proven to be effective and safe through carefully conducted clinical trials.

Unfortunately, older cancer patients rarely participate in clinical trials. Because most cancer trials do not include sufficient numbers of older patients, there is not enough data to determine safety or efficacy for most cancer treatments in this population. The challenge of enrolling older cancer patients in clinical trials becomes more urgent as the number of older individuals in the United States increases. The Southwest Oncology Group (SWOG) is studying why older cancer patients either do or do not enroll on a cancer clinical trial. They hope to explore and define the barriers to clinical trials participation in older patients and develop successful interventions to overcome them.

A window of opportunity exists to forge new directions in cancer diagnosis, treatment and prevention, resulting from recent developments that create an unprecedented juncture in science and technology. New microarray technologies can identify genes and proteins involved in pathways that control cell proliferation, death, and differentiation. Evaluation of these genes and gene products in human tumors is the next critical step to assess their real clinical value.

A new method for rapid evaluation of large numbers of tumor samples at the same time, called tissue microarray, has been developed. This high-throughput technique can greatly expand our ability to test tumor markers identified through new array technologies, and rapidly translate molecular discoveries into clinical applications. The SWOG researchers propose to construct tissue microarrays (single paraffin blocks that contain small cores from hundreds of different tumors) from tumor samples that have been collected as part of the Southwest Oncology Group, an NIH-funded national cancer clinical trials cooperative research group.

Using this method, patient samples from an entire clinical trial can be analyzed by testing a few master slides instead of testing hundreds of conventional single slides. The tumor samples from the clinical trials constitute a unique resource that can be used to answer questions that cannot be answered in any other kind of study. For example, studies to identify tumor characteristics associated with response to a particular therapy or factors related to racial or age-related differences in breast cancer outcome would all be possible in a relatively short time. Using the tissue microarrays constructed from SWOG tumor samples, investigators nationwide will be able to test hypotheses and answer clinical research questions that could positively affect breast cancer patients throughout the world.

Metastases involving the bone are common in advanced breast cancer patients. Bone is the first site of distant recurrence in 25-40% of metastatic breast cancer cases. There is a synergistic interaction between the bone environment and breast cancer cells that enables bone cells to stimulate the growth and survival of breast cancer cells that migrate to the area. Bisphosphonates are a class of drugs that have a strong effect on bone, with their primary role being to inhibit the action of a type of bone cells called osteoclasts that are associated with bone breakdown. Bisphosphonates have been shown to strengthen bones in patients with osteoporosis, and in low doses are frequently used for this indication. In high doses, bisphosphonates have been shown to reduce bone destruction and improve bone symptoms in advanced breast cancer patients with bone metastases.

Small studies from Europe suggest that it is possible that these agents can also reduce and/or prevent the later occurrence of bone metastases when given to newly diagnosed, early stage breast cancer patients. A large, randomized, 4,500-patient multicenter trial (SWOG S0307) is currently ongoing to determine whether adjuvant bisphosphonates can prevent bone metastasis and improve survival in early stage breast cancer patients. It will be important to determine what risks are involved in the use of high-dose bisphosphonates in this setting. Companion studies to S0307 will look at the effect that high dose bisphosphonates have on bone quality and quantity by using bone biopsies, bone density scans, and blood and/or urine markers of bone turnover. The investigators hope to determine if long term use of high doses of bisphosphonates has a detrimental effect on bone.

Finally, over the coming year, the SWOG investigators will apply BCRF funds to the development and initiation of the following proposed trials: Treatment of Invasive Residual Disease after Preoperative Chemotherapy; a Post-Lymphoma Breast Cancer Registry; and Evaluating the Impact of Adding Serial Serum Tumor Marker Testing to Routine Follow-up of High-Risk, Stage II-III Breast Cancer Patients on Overall Survival.

2) On behalf of Memorial Sloan-Kettering Cancer Center, The Breast International Group (BIG) and The Breast Cancer Intergroup of North America (TBCI)
Co-Investigators: Fatima Cardoso, MD, Jules Bordet Institute, Belgium; Monica Morrow, MD, Memorial Sloan-Kettering Cancer Center; Martine J. Piccart-Gebhart, MD, PhD, Jules Bordet Institute, Beldium; William C. Wood, MD, Emory University

In contrast to women, men rarely develop breast cancer. In the US, less than 1% of all breast cancers are diagnosed in men. Doctors have a limited understanding of how to approach such an uncommon disease. Most decisions regarding treatment are based upon large clinical trials involving only women with this disease. However, there are important differences regarding the age at diagnosis, underlying risk factors, and biological characteristics which suggest that male breast cancer (Male BC) may be a distinct disease.

In order to develop more appropriate treatment recommendations, a better understanding of the natural history and biology of Male BC is desperately needed. Due to the rarity of this disease, such insight can only be gained through co-operation between hospitals in different countries worldwide. The Breast International Group, the Breast Cancer Intergroup of North America and Memorial Sloan-Kettering Cancer Center have joined forces to launch a three-part International Program on Male Breast Cancer (International Registration and Biologic Characterization Program).

The first part of this Program consists of a retrospective joint analysis of a very large series of men previously diagnosed with breast cancer. This initiative will gather data regarding patient characteristics, tumor features, treatment and outcome for more than 1600 men diagnosed with breast cancer over the last 20 years. Tumor specimens (both paraffin-embedded and frozen) from a large proportion of these patients will be collected and centrally analyzed, to understand the biological characteristics of this disease and to identify important potential prognostic (indicative of the good or bad outcome of the disease) and predictive (indicative of probability of response to certain therapies) markers, which will then be validated in the third part of the Program.

This important study will provide invaluable information regarding the behavior of this rare disease and, combined with the information gathered during the second part of the Program (an international Male BC registry), will form the basis and rationale for the design of an international Male BC clinical trial.

Bio:
Julie Gralow majored in Biologic Sciences as an undergraduate at Stanford University, attended medical school at the University of Southern California in Los Angeles, and trained as a resident in Internal Medicine at Brigham and Women's Hospital in Boston. Her Medical Oncology fellowship training was performed at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center.

As a breast cancer specialist and academician, Dr. Gralow's time is split between patient care, education, and clinical research. She is the principal investigator on several clinical trials related to breast cancer prevention and treatment, and is committed to patient education, outreach and wellness. She is co-chair of the Southwest Oncology Group’s Breast Cancer Committee, and serves as chair of the American Society of Clinical Oncology's Cancer Communications Committee.

Dr. Gralow is also Medical Director, Team Physician and co-founder of Team Survivor Northwest, an exercise and fitness program for women cancer survivors. She is co-author of "Breast Fitness: An Optimal Exercise and Health Plan for Reducing Your Risk of Breast Cancer".