Problems involved in including women with simple hysterectomy in epidemiologic studies measuring the effects of hormone replacement therapy on breast cancer risk.

A number of epidemiologic studies of breast cancer risk have classified women who reported undergoing simple premenopausal hysterectomy without bilateral oophorectomy as being postmenopausal at the age when natural menopause has occurred in a high percentage (S:90 percent) of women (1-3). We demonstrate below that this approach to the inclusion of women with simple hysterectomy leads to an underestimate of the effect of age at menopause on breast cancer risk, as well as an underestimate of the effect of hormone replacement therapy (HRT) on breast cancer risk. Other epidemiologic studies of breast cancer have included women with simple hysterectomy in their analyses by setting the woman's age at menopause equal to her age at hysterectomy, with the inclusion of an indicator variable for this category of women (4). We demonstrate below that this approach also leads to biased results, again underestimating the impact of age at menopause and of HRT use on breast cancer risk.