Peggy L. Porter, MD

2012-2013 BCRF Projects:
(made possible by generous support from Play for P.I.N.K.)
1) On behalf of SWOG
Co-Investigator: Julie R. Gralow, MD, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle

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, and data are 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.

Male Breast Cancer Study
Dr. Porter is taking part in a second project initiated by BCRF-funded grantees. Due to the low incidence of male breast cancer, international cooperation is necessary to undertake relevant projects with potential clinical impact. With the support of BCRF, 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 about 1,500 male breast cancer cases are being collected. Accrual to these studies is happening rapidly, and over 400 patients have registered. This is the largest study on male breast cancer to date. The pathology analysis of these tumor samples in the central labs 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. The second part of this program, a prospective registry, is about to be launched.

Mid-year Progress: To date, 700 patients registered for this study, which represents the largest study of male breast cancer ever undertaken. The pathology analysis of these tumor samples in the central labs will begin when all samples are received 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. The second part of this program, a prospective registry, is being launched.

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. Porter obtained her medical degree in 1987 from the University of New Mexico and completed her residency in Pathology at the University of Washington where she was a recipient of the American Cancer Society Clinical Oncology Fellowship. She joined the FHCRC in 1993. Her lab focuses on identifying and understanding the molecular events associated with initiation and progression of human cancer, particularly the role of abnormal cell cycle control. In collaboration with epidemiologists and basic science researchers at the FHCRC, studies in the Porter lab identified the loss of cell cycle inhibitor p27 as an important indicator of poor prognosis in breast cancer. Investigations are underway to evaluate the relationship of p27 loss, along with abnormalities in other cell cycle regulators, with response or failure to specific chemotherapeutic agents.

As head of the multi-institutional Breast Cancer Program centered at the FHCRC, Dr. Porter leads a dynamic group of basic scientists, epidemiologists, surgeons, oncologists and pathologists dedicated to reducing the incidence and subsequent mortality of breast cancer. Projects by members of the program range from mapping mutations that contribute to cancer risk to evaluating life-style factors and potential interventions. Dr. Porter joined the Southwest Oncology Group in 2000 and is working actively with the Breast Committee, led by Dr. Robert Livingston, to take advantage of new technologic developments that will broaden the scope of clinical research questions that can be asked and answered in the clinical trials setting.