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BCRF Grantee Since

2002

Donor Recognition

The Play for P.I.N.K. Award

Area(s) of Focus

Julie R. Gralow, MD

Jill D. Bennett Professor of Breast Cancer
Professor of Medical Oncology
University of Washington School of Medicine
Director, Breast Medical Oncology
Seattle Cancer Care Alliance
Associate Breast Cancer Program Head
Fred Hutchinson Cancer Research Center
Seattle, Washington

Current Research

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 2013-2014.

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.

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.

Male Breast Cancer Study
Due to the rarity of the male breast cancer, international cooperation is necessary to undertake relevant projects with potential clinical impact. With BCRF support, the Male Breast Cancer International Registration and Biologic Characterization Program has been launched, as a joint effort between the Breast International Group (BIG) and the North American Breast Cancer Groups (NABCG) and coordinated by the European Organization for the Research and Treatment of Cancer (EORTC). In the first part of this program, clinical data and tumor samples from male BC cases treated in the last 20 years are being collected. Patients are accruing rapidly, with about 1600 patients registered, which makes this study the largest series of male breast cancer cases ever investigated. The pathology analysis of these tumor samples in the central labs has begun and will lead to a better understanding of the biological characteristics of this disease and to the identification of important potential prognostic (indicative of the good or bad outcome of the disease) and predictive (indicative of probability of response to certain therapies) markers. In 2013-2014, this international team plans to launch the second part of this program, a prospective registry, and will continue negotiations for the third part, a prospective clinical trial. finalized.

RxPONDER Trial
RxPONDER(Rx for Positive Node, Endocrine Responsive Breast Cancer) (S1007) is a clinical trial led by the national clinical trial cooperative group SWOG, done through The North American Breast Cancer Group (NABCG). It is a Phase III randomized clinical trial of best endocrine therapy versus best endocrine therapy and chemotherapy. The goal of the study is to determine the effect of chemotherapy in patients with node positive and HR-positive disease who do not have high recurrence score (RS). Patients with histologically confirmed diagnosis of node positive invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, have their tumors tested with the Oncotype DX assay. If the recurrence score is equal or less than 25 (low or intermediate RS), patients are eligible for randomization. This is the perfect opportunity to do systematic research to compare the clinical effectiveness and cost-effectiveness of breast cancer care based on genomic tools and markers compared to existing standards of care that do not use genome-based approaches. The researchers believe that this study will answer one of the most important scientific and clinical questions in breast oncology, and if successful, would be a practice-changing trial for these patients.

In 2013-2014, BCRF funds will support the participation of Spanish Breast Cancer Research Group (GEICAM) in the study. Since GEICAM’s founding in 1995, a total of 43,571 patients have been enrolled in 99 national and international clinical trials. At present, more than 180 hospitals in Spain are involved in the network. The BCRF grant will be used to cover logistics expenses for informed consent process, patient accrual, data collection, data management, sample collection and shipment, pharmacovigilance activities, protocol amendments, IRB costs and the costs of other regulatory processes."

Mid-Year Summary

For the S0307 (AZURE) trial , the researchers report that a safety monitoring committee reviewed the data of patients through October 2013 and toxicities will now be analyzed and reviewed further. For the Predictors of Bone Metastases study, a selection of matched controls from a related study is pending.

The retrospective component of the international Male Breast Cancer study has completed accrual of greater than 1200 patients. The researchers are currently planning a prospective study to assess long-term outcomes in male breast cancer patients. Current efforts are aimed at recruiting male breast cancer patients who have been seen at the SCCA and Harborview Hospital. Additionally, Drs. Gralow and Porter and their team are planning targeted recruit efforts through the advocacy community. The prospective component of the study is in the final planning stages, and the Washington researcher expect to send this to their institutional review board within the next six months.

The construction of tissue microarray (TMA) from tumor samples collected in clinical trials significantly increases the value of the trials. Using this tool, hundreds of tumor samples can be simultaneously tested for tumor-related biomarkers. To assess the expression of potential targets for treatment, such as tubulins, in SWOG clinical trials, the Porter laboratory has constructed tissue microarrays (TMAs) for SWOG phase II trials and larger SWOG-led phase III Intergroup breast cancer studies clinical trials. The researchers continue to evaluate tumors in the unique S9313 clinical trial for biomarkers that will help them to understand the factors related to survival of women with breast cancer treated with anthracycline-based therapy. New tissue microarray blocks are being constructed so that this unique resource can continue to be used for studies of novel markers.

Specifically, the researchers are assessing over 2000 tumors for breast cancer subtype (triple negative and luminal A and B) and expression of ALDH, ER, PR, HER2 and Ki-67. New studies include evaluation of BRCA expression and methylation in triple negative breast cancers identified in the trial. The Cancer Research and Biostatistics (CRAB) group is analyzing the data from these BCRF-funded studies . Previously published and new results from the S9313 trial are helping researchers better understand response to this important and commonly used chemotherapeutic agent.

RxPONDER Trial
RxPONDER(Rx for Positive Node, Endocrine Responsive Breast Cancer) (S1007) is a clinical trial led by the national clinical trial cooperative group SWOG, done through The North American Breast Cancer Group (NABCG). It is a Phase III randomized clinical trial of best endocrine therapy versus best endocrine therapy and chemotherapy. The goal of the study is to determine the effect of chemotherapy in patients with node positive and HR-positive disease who do not have high recurrence score (RS). Patients with histologically confirmed diagnosis of node positive invasive breast carcinoma with positive estrogen and/or progesterone receptor status, and negative HER-2, have their tumors tested with the Oncotype DX assay. If the recurrence score is equal or less than 25 (low or intermediate RS), patients are eligible for randomization. This is the perfect opportunity to do systematic research to compare the clinical effectiveness and cost-effectiveness of breast cancer care based on genomic tools and markers compared to existing standards of care that do not use genome-based approaches. The researchers believe that this study will answer one of the most important scientific and clinical questions in breast oncology, and if successful, would be a practice-changing trial for these patients.

In 2013-2014, BCRF funds will support the participation of Spanish Breast Cancer Research Group (GEICAM) in the study. Since GEICAM’s founding in 1995, a total of 43,571 patients have been enrolled in 99 national and international clinical trials. At present, more than 180 hospitals in Spain are involved in the network. The BCRF grant will be used to cover logistics expenses for informed consent process, patient accrual, data collection, data management, sample collection and shipment, pharmacovigilance activities, protocol amendments, IRB costs and the costs of other regulatory processes. "

Mid-Year Summary:
SWOG Rx Ponder Trial: BCRF is a major funder of the S1007 genomic tests. Funding for the current year is ensuring success in trial accrual through support of the leading international contributor- GEICAM. GEICAM is the major Spanish clinical trials cooperative group, which was impacted significantly with the downturn in the Spanish economy. Their participation in S1007 was tenuous in Oct 2013. Thanks to BCRF, GEICAM continues to engage approximately 17% of the patients in this trial. The study is actively accruing at 20 centers in Spain. 566 patients have been registered and have had tissues tested or are participating in on-going testing for Oncotype DX; 341 have been randomized ahead of the estimated accrual goals. As of January 1, 2014, accrual for the trial is ahead of schedule.

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.

Co-Investigators