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Impact of aging on the biology of breast cancer
Christopher C. Benz, MD
Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
Accepted 5 September 2007
1. Breast cancer: a heterogeneous age-associated malignancy
2. Normal mammary gland changes with aging and menopause
3. Tumorigenic predisposition within the aging mammary gland
3.1. Timing of carcinogenic events
3.2. Persistence with aging of breast epithelium susceptible to transformation
4. Cellular mechanisms linking aging and cancer
4.1. Do late-onset breast cancers derive from senescent stroma or epithelium?
4.2. Do cancer-aging hypotheses predict clinical breast cancer behavior?
5. Biological differences between early-onset and late-onset breast cancers
5.1. Inverse age relationship between ER and measures of breast cancer growth and genome stability
5.2. Aging and measures of breast cancer invasiveness and angiogenesis
5.3. Early-onset and late-onset breast cancers arise by epigenetically different mechanisms
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Irmgard Irminger-Finger Ph.D., Molecular Gynecology and Obstetrics Laboratory, Department of Gynecology and Obstetrics, University Hospitals Geneva, Maternit'e,
30 Blvd de la Cluse, Geneva 1211, Switzerland.
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The author wishes to expresses sincere appreciation to his many coauthors who contributed to the original studies discussed herein; particularly noteworthy are his longstanding collaborations with Ann D. Thor, Dan H. Moore, Joe W. Gray, Donna Albertson, Serenella Eppenberger-Castori, and Urs Eppenberger. Outstanding contributions by investigators-in-training, Vita Fedele and Christina Yau, were critical to furthering our understanding of this important area of breast cancer research. Lastly, the comments of Judy Campisi, Ph.D., were most helpful in the preparation of this manuscript. The author's studies were supported in part by National Institute of Health grants R01-AG020521, R01CA71468, P01-AG025901, and P50-CA58207; California Breast Cancer Research Program grant 10YB-0125; and Hazel P. Munroe memorial funding to the Buck Institute.
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Christopher C. Benz, M.D., Director of Buck Institute Program on Cancer and Developmental Therapeutics, and adjunct professor of medicine in UCSF Division of Hematology-Oncology and Comprehensive Cancer Center, earned his B.S. in biochemistry at University of California, Los Angeles (UCLA) in 1968, and M.D. at University of Michigan School of Medicine (Ann Arbor) in 1972. He completed his internal medicine and oncology specialty training at the Vancouver General Hospital, University of British Columbia in 1978, and then finished his postdoctoral training and joined the medical faculty at Yale University School of Medicine. In 1983 he was recruited to join the Division of Hematology-Oncology (Department of Medicine) and Cancer Research Institute of the University of California, San Francisco (UCSF) and, shortly thereafter, also became a member of the Joint UCSF/UC Berkeley Bioengineering Graduate Program. In 2000, Dr. Benz relocated his 20-yearold federally funded UCSF breast cancer research program to become one of the founding faculty of the newly opened Buck Institute for Age Research in Novato, CA. He continues to maintain his professorship at UCSF, cares for patients at the UCSF/Mt. Zion Breast Care Clinic, and plays an active role as senior member of the UCSF Comprehensive Cancer Center's Breast Oncology Program.
As Director of the Buck Institute's Program on Cancer and Developmental Therapeutics, Dr. Benz's translational research program focuses on identifying molecular strategies to improve breast cancer diagnostics and therapeutics, with a special emphasis on trying to understand and interrupt the link between breast cancer and aging. He has published nearly 200 peer-reviewed manuscripts and serves on multiple national and international review and oversight committees, including the National Cancer Institute's DTP/DCTD Biological Resources Branch Oversight Committee and the American Association of Cancer Research's Task Force on Cancer and Aging.
Tel.: +1 415 209 2092; fax: +1 415 209 2232.
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Please cite this article in press as: Benz CC, Impact of aging on the biology of breast cancer, Crit. Rev. Oncol./Hematol. (2007), doi:10.1016/j.critrevonc.2007.09.001
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