Paolo G. Toniolo
Nelson Institute of Environmental Medicine and Kaplan Cancer Center, New York University School of Medicine, New York, New York
It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu. Nearly all the epidemiological studies conducted in the 1970s and 1980s were hospital-based case-control studies in which specimen sampling was performed well after the clinical appearance of the disease. Early prospective cohort studies also had limitations in their small sample sizes or short follow-up periods. However, more recent case-control studies nested within large cohorts, such as the New York University Women's Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are generating new data indicating that increased levels of estrone, estradiol and bioavailable estradiol, as well as their androgenic precursors, may be associated with a 4- to 6-fold increase in the risk of postmenopausal breast cancer. Further new evidence, which complements and expands the observations from the latter studies, shows that women with the thickest bone density, which may be a surrogate for cumulated exposure to hormones, experience severalfold increased risk of subsequent breast cancer as compared to women with thin bones. These data suggests that endogenous sex hormones are a key factor in the etiology of postmenopausal breast cancer. New prospective cohort studies should be conducted to examine the role of endogenous sex hormones in blood and urine samples obtained early in the natural history of breast cancer jointly with an assessment of bone density and of other important risk factors, such as mammographic density, physical activity, body weight, and markers of individual susceptibility, which may confer increased risk through an effect on the metabolism of endogenous hormones or through specific metabolic responses to Western lifestyle and diet. -- Environ Health Perspect 105(Suppl 3):587-592 (1997)
Key words: breast neoplasms, estrogens, estrone, estradiol, sex hormone-binding globulin
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 6 June 1996; manuscript accepted 18 December 1996.
Supported by research grant CA34588 and by center grants CA16087 and ES00260 from the National Institutes of Health.
Address correspondence to Dr. P. Toniolo, New York University School of Medicine, 341 East 25th Street, 2nd floor, New York, NY 10010-2598. Telephone: (212) 263-6499. Fax: (212) 263-8570. E-mail: paolo.toniolo@ccmail.med.nyu.edu
Abbreviation used: SHBG, sex hormone-binding globulin.
Last Update: April 10, 1997