Postmenopausal Estrogen-Progestin Therapy in Relation To Cancers of the Endometrium and Breast

Abstract

Under the direction of Drs. Shirley Beresford and Janet Stanford, population-based case-control studies of endometrial and breast cancer have been completed in western Washington State during the past year. In-person interviews were obtained with women diagnosed with one of these conditions, and the responses were compared to those of a random sample of female residents of the same area.

As had been noted in a previous study of endometrial cancer in the same population, among estrogen users a supplementary progestational agent was taken more commonly by controls than cases. However, the risk of endometrial cancer was reduced to that of an estrogen non-user only if: a) progestin use occurred for 10 or more days per month; and b) such use had not been preceded by several years of unopposed estrogens. A similar proportion of breast cancer cases and controls had taken unopposed estrogens; neither was there any difference in the use of estrogens accompanied by a progestin. Long-term use of an estrogen/progestin combination was associated with, if anything, a decreased risk of breast cancer relative to hormone non-users.

The results of these studies suggest that the addition of a progestational agent to a regimen of postmenopausal estrogen therapy does not have an adverse effect on the incidence of breast cancer and affords at least partial protection against the occurrence of endometrial cancer.

Estrogen preparations are used by a great number of postmenopausal women, due both to their short-term influence on symptoms and their longer-term benefit with respect to skeletal strength and reduced risk of coronary heart disease. The potential of these hormones to predispose to the occurrence of endometrial cancer has led many physicians to prescribe a combination of estrogen plus progestin (E+P; combined hormone therapy). While this combination appears to offset the risk of endometrial cancer associated with estrogen use to at least some extent (1), the dose and/or duration of progestin that is optimal in this (and other) regard(s) is uncertain. Furthermore, the potential influence of combination therapy on cancers developing in other hormonally-sensitive organs, e.g., the breast, has only begun to be explored in epidemiologic studies (2).

Two parallel case-control studies have been performed by investigators at the Fred Hutchinson Cancer Research Center and the University of Washington to address these issues. The first, on endometrial cancer, was conducted by Shirley Beresford, Lynda Voigt, Noel Weiss, and Barbara McKnight. The second, on breast cancer, was conducted by Janet Stanford, Noel Weiss, Lynda Voigt, and Janet Daling.