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BCRF Grantee Since


Donor Recognition

The Eisai Oncology Award

Area(s) of Focus

Daniel F. Hayes, MD

Stuart B. Padnos Professor of Breast Cancer Research
Clinical Director, Breast Oncology Program
University of Michigan
Ann Arbor, Michigan

Current Research

Project 1: The North American Breast Cancer Group (NABCG) has prospectively collected and stored breast cancer tissues and other biospecimens (blood, serum, DNA, etc.) from patients who participated in prospective randomized clinical trials. These samples are available for studies of new or promising tumor markers. A Correlative Science Committee (CSC) rigorously reviews submitted concepts to decide which should go forward.

Since 2006, BCRF has supplied support for ongoing activities of the CSC, including support for approved studies, for infrastructure projects related to archived specimens, and collaborations with the Breast International Group (BIG).

BCRF has supplied support for ongoing activities of the Correlative Science Committee. These include the following initiatives:

  • Research grants to individual laboratory investigators to conduct correlative science studies
  • Infrastructure grants to the Pathology Coordinating Offices of the individual cooperative groups to support construction of tissue microarrays (TMAs), ha rvesting of DNA and RNA, and staining of tissue sections for standard markers, such as estrogen receptor and HER2
  • Support of workshop meetings between investigators in NABCG and other investigators in related fields
  • Support of the Breast International Group (BIG) for the following activities
  • Development of a BIG correlative science website ( which is linked to the NABCG CSC website (
  • Generation of TMAs from selected studies conducted by BIG
  • Staining of these TMAs for standard markers

Over the last half-decade, at least 15 papers and reports at major scientific meetings have been published by funded investigators. Inventories of the archived tissues are now publicly available, and these specimens have been centrally evaluated for ER, PgR, and HER2. Major workshops have led to initiatives within the NABCG for pharmacogenomics and to standardize assays for an important biomarker, Ki67.

In this funding period, NABCG will continue to provide support to investigators whose concepts are approved by the NABCG CSC; to the pathology offices of the various cooperative groups to build new TMAs, perform routine marker analyses, and harvest nucleic acids; to the International Ki67 Working group, and to BIG to further support their translational science activities. The NABCG also will plan a workshop to consider correlative studies within the TAILORx study. They wish to establish a Translational Science Fellowship to support a junior investigator with an interest in translational science to work with senior members of the NABCG/BIG and the Secretariat of the Oxford Overview Collaboration to pursue the objectives of the “TransOx” committee. Finally, the research group will continue efforts and studies to standardize immunohistochemistry staining of Ki67 so that measure of proliferation can be done routinely on NABCG/BIG archived specimens, and so that Ki67 can be used with confidence in routine clinical practice.

Project 2: Co-Investigator: James M. Rae, PhD, University of Michigan, Ann Arbor, MI

The primary goal of Drs. Hayes and Rae's research is to identify genetic markers that can be used to predict whether an individual patient will respond to and tolerate specific anti-estrogen breast cancer therapies. To this end, they have been genotyping patients from two of the largest clinical trials that tested the efficacy and safety of tamoxifen and aromatase inhibitors (AIs), the “Intergroup Exemestane Study” (IES) and the “Arimidex, Tamoxifen, Alone or in Combination” Trial (ATAC). Drs. Hayes and Rae recently published their results showing that CYP2D6 genotype does not predict response to tamoxifen therapy in patients enrolled in ATAC. They have also completed analysis of an independent validation set using patients enrolled in IES. They have now genotyped nearly 1,200 patients for CYP2D6 alleles, and completed their statistical analyses testing for possible associations between CYP2D6 genotype and response to tamoxifen and exemestane (as a control group). The researchers failed to detect an association between CYP2D6 genotype and response in this patient population. The results from IES reconfirm their findings from ATAC. Both studies did not support the hypothesis that CYP2D6 genotype predicts clinical benefit from adjuvant tamoxifen treatment among postmenopausal breast cancer patients, and Drs. Hayes and Rae conclude that CYP2D6 genotype should not be used clinically to determine the use of tamoxifen. Having successfully completed their analyses of CYP2D6, this group has begun a series of studies examining additional gene variants for their possible association with response to anti-estrogen therapy in both the ATAC and IES trials.

Mid-Year Summary

Project 1: In the last six months, BCRF funding to Dr. Hayes to support correlative science studies through the North American Breast Cancer Group (NABCG) has accomplished the following:

  • Provided funding to the ECOG tissue bank for further production of tissue microarrays (TMAs)
  • Provided funding to the Breast International Group for two projects related to the now fully-accrued SOFT and TEXT clinical trials:
  • Collection of breast cancer tissues from patients from North America who participated in these trials
  • Production of TMAs and harvesting of nucleic acids from the tissue blocks collected from all patients who participated in the trials
  • Made further progress within the International Ki67 working group to standardize analysis of this critical biomarker within the cooperative groups around the world, including publication of a landmark paper (Polley MY, Leung SC, McShane LM, et al. An international ki67 reproducibility study. J Natl Cancer Inst 2013;105:1897-906) and an oral presentation at the 2013 San Antonio Breast Cancer Symposium (Nielsen T, et al) describing the results of phase I and II studies to date.

In this funding period, Dr. Hayes will continue to provide support to investigators whose concepts are approved by the NABCG CSC, to the various cooperative groups to build new TMAs, perform routine marker analyses, and harvest nucleic acids, to the International Ki67 Working group to proceed into phase III of their efforts to standardize this marker, and to BIG to further support their translational science activities. They will also convene a workshop to consider correlative studies within the TAILORx study in March, 2014.

Project 2: Drs. Rae and Hayes are now conducting a large series of genetic analyses in these patient populations in order to test the clinical utility of additional proposed genetic markers of anti-estrogen response and side effects. They anticipate that successful completion of their studies will lead to personalized endocrine therapy based on the patient’s unique genetic makeup.


Daniel Fleming Hayes, MD, is the Director of the Breast Oncology Program at the University of Michigan Cancer Center, where he is also a Professor of Medicine. The University of Michigan is a federally designated Comprehensive Cancer Center that has placed a particular emphasis on cancer research that translates exciting findings from the laboratory to the clinic.

Over nearly twenty years, Dr. Hayes professional training and career have been directed toward bridging the gap between laboratory and clinical research. He received a bachelor's degree (1974) in biology and a master's degree (1977) in biochemistry at Indiana University. He received his MD from the Indiana University School of Medicine in 1979, followed by a residency in internal medicine at the University of Texas Health Science Center at Dallas, Texas (Parkland Memorial and affiliated hospitals). He served a fellowship in medical oncology from 1982-1985 at Harvard's Dana- Farber Cancer Institute in Boston, where he subsequently distinguished himself on the faculty in regards to breast cancer research and care. In 1992, he assumed the role as the Medical Director of the Breast Evaluation Center at DFCI. He held that title until 1996, when he moved to Georgetown University and spent the succeeding five years establishing an enormously successful collaboration with Dr. Marc E. Lippman. In 2001, both Drs. Lippman and Hayes joined the already prestigious University of Michigan Cancer Center to continue their fruitful relationship in the context of the existing translational science.

Dr. Hayes has been influential in both clinical and laboratory studies of the diagnosis and treatment of breast cancer. With his long-time colleague, Dr. Donald Kufe, Dr. Hayes published the first reports concerning the development of the CA15-3 blood test, which is currently used world-wide to evaluate patients with breast cancer. He has become an internationally recognized leader in the use of this and other tumor markers, such as HER-2. More recently, he and his colleagues have reported ground breaking results regarding circulating tumor cells in metastatic breast cancer and regarding the pharmacogenomics of tamoxifen. He is widely considered to be an expert in the field of clinical research of breast cancer, especially in regards to new hormonal and chemotherapeutic treatments. He also lectures and publishes extensively regarding the management of patients with breast cancer.

Reflecting his expertise, Dr. Hayes has been Chair of the Solid Tumor Correlative Sciences Committee of the Cancer and Leukemia Group B (CALGB), one of the leading federally-funded multi-institutional cooperative groups that perform definitive clinical research in cancer care and he now hold similar positions in the Southwest Oncology Group and the U.S. Breast Cancer Intergroup. He co-chairs the Expert Panel for Tumor Marker Practice Guidelines for the American Society of Clinical Oncology, and he is on the editorial boards of several leading cancer journals.

Dr. Hayes lives in Ann Arbor with his wife, Jane.

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