Julie R. Gralow, MD

BCRF has supported several SWOG initiatives led and coordinated by Drs. Gralow and Porter. Among these endeavors are a phase III clinical trial of bisphosphonates as adjuvant therapy for primary breast cancer (S0307), the SWOG tissue microarray resource, the clinical and biological characterization of male breast cancer, and predictors of bone metastases. These projects will remain the focus of BCRF-supported studies in 2012-2013.

Impact of Bisphosphonates on Bone Quality
The S0307 clinical trial, called AZURE, continues to follow-up and monitor volunteers. All 6,097 patients have been followed for at least one year, and no patients remain in the monthly dosing portion of the zoledronic therapy. These patients will be followed closely for recurrence for up to ten years. A recent presentation of this clinical trial findings occurred at the San Antonio Breast Cancer Symposium in December 2010. The conclusion, with the combined evidence of other trials, regarding whether adjuvant bisphosphonates reduce recurrence or death due to breast cancer and in which patient populations, remains unclear, and further study is warranted. S0307 will continue as planned. The first interim analysis took place in early October 2011 and the next one is scheduled to take place in fall 2012.

Mid-year progress: As of February 2013, all 6,097 patients of the AZURE trial have been followed for at least two years, and they will continue to be followed closely for recurrence for up to ten years. The conclusion, with the combined evidence of other trials, regarding whether adjuvant bisphosphonates reduce recurrence or death due to breast cancer and in which patient populations, remains unclear and further study is warranted. A safety monitoring committee reviewed the data of patients through October 2012 and recommended that the patients who received treatment on study continue to be followed long term as planned. The researchers will review the data collected from the study patients every six months.

Predictors of Bone Metastases
In the predictors of bone metastases study, 93 patients with distant recurrence have been identified, and tissue microarrays of 80 patients and slides from 13 patients have been created using their specimens. Clinical/pathological information has been finalized, and initial lab work was performed with related data finalized. Further lab work is pending from collaborators at Amgen. Preliminary analysis of the data set confirmed that ER positivity is related to higher probability of bone metastasis. A selection of matched controls from a related study is pending. Further tests are still being conducted with data yet to be analyzed and finalized.

Mid-year Progress:To date, the team continues to finalize clinical and pathological information on collected samples, and initial lab work was performed with related data finalized. Further lab work is pending from collaborators from industry.Preliminary analysis of their data set confirmed that ER positivity is related to higher probability of bone metastasis. A selection of matched controls from a related study is pending.

Tissue Microarray
The construction of tissue microarrays (TMAs) from tumor samples collected in clinical trials significantly increases the value of the trials. To assess the expression of potential targets for treatment, such as tubulins, in SWOG clinical trials, Dr. Porter's laboratory has constructed TMAs for SWOG phase II trials and larger SWOG-led phase III Intergroup breast cancer studies clinical trials. Another study is underway using the S9313 TMA that aims to test the relationship of ALDH expression and survival from breast cancer in patients treated with anthracycline-based therapy. ALDH is a marker of breast cancer stem cells, which have been shown to be associated with resistance to chemotherapy in vitro. The assessment of ALDH is complete and the data are currently being analyzed.

Over the past funding period, researchers led by Drs. Gralow and Porter conducted central evaluation of estrogen receptor (ER) in tumor samples collected from the S9313 clinical trial. This evaluation of over 2,000 tumors for expression of ER is now complete, and data have been analyzed. A manuscript describing these findings is underway.

Additional analyses, made possible with the funding from BCRF, are being done to better understand the relationship of "normal" HER2 and clinical outcome for women in the S9313 clinical trial who received chemotherapy. For example, the researchers continue to evaluate tumors from the trial for biomarkers, such as progesterone receptor (PR) and the cell proliferation marker, Ki-67, which will help them understand the factors related to survival of women with breast cancer treated with anthracycline-based therapy. The investigators anticipate that results from this study will help improve understanding of response to this important and commonly used chemotherapeutic agent.

Bio:
Dr. 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.

At the University of Washington School of Medicine, Dr. Julie Gralow, professor (Medical Oncology), is the inaugural holder of the Jill D. Bennett Endowed Professorship in Breast Cancer. In addition, she has been a professor of medicine since 2009 and director of Breast Medical Oncology at the Seattle Cancer Care Alliance since 2007.

Also, Dr. Gralow is 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.