814 - REVIEW Relationship Between Estrogen Levels, Use of...

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REVIEW Relationship Between Estrogen Levels, Use of Hormone Replacement Therapy, and Breast Cancer Graham A. Colditz* We sought to determine the strength of the evidence suggest- ing that estrogen and postmenopausal replacement hor- mones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE® on hormones and breast cancer, including re- ports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link be- tween environmental factors and disease were used to review the evidence for a causal relationship between female hor- mones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose–response pattern, biologic plausibility, temporality, strength of asso- ciation, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The posi- tive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hor- mones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relation- ship between use of estrogens and progestins, levels of en- dogenous estrogens, and breast cancer incidence in post- menopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal symptoms and the long-term preven- tion of osteoporosis and heart disease. [J Natl Cancer Inst 1998;90:814–23] During the past 40 years, we have moved from a period when the use of postmenopausal estrogen was advocated to reduce the risk of breast cancer to the present, when a plethora of epide- miologic studies suggests a positive relationship between estro- gen levels, markers of estrogen exposure, the use of estrogens after menopause, and an increased risk of breast cancer. Numer- ous meta-analyses of the published studies concerning the use of postmenopausal hormones provide a quantitative summary of the field, indicating that a significant relationship exists between the duration of use of postmenopausal hormones and the risk of breast cancer (1,2). Furthermore, the combined reanalysis of original data from 51 epidemiologic studies that included more
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This note was uploaded on 02/17/2011 for the course CHEMISTRY 101 taught by Professor Csr during the Spring '11 term at University of Louisville.

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814 - REVIEW Relationship Between Estrogen Levels, Use of...

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