© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 814-823, Copyright © 1998 by Oxford University Press
GA Colditz
We sought to determine the strength of the evidence suggesting that
estrogen and postmenopausal replacement hormones play a role in the
development of breast cancer. We reviewed the existing English language
literature in MEDLINE on hormones and breast cancer, including reports 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 between environmental
factors and disease were used to review the evidence for a causal
relationship between female hormones 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 association, 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
positive relationship between endogenous hormone levels in postmenopausal
women and risk of breast cancer supports a biologic mechanism for the
relationship between use of hormones 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 relationship between use of estrogens
and progestins, levels of endogenous estrogens, and breast cancer incidence
in postmenopausal 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 prevention of osteoporosis and heart disease.
REVIEWS
Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, and The Harvard Center for Cancer Prevention, Boston, MA 02115, USA.
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