Hormone replacement therapy in patients at high risk of developing breast cancer: The use of a combined risk model

Abstract

Controversy surrounds the use of hormone replacement therapy (HRT) in patients who have concomitant risk factors for the development of breast cancer. In this study, we review data reported in meta-analyses on breast cancer risk with HRT use. The hypothesis is tested that HRT and pre-existing risk factors would act in synergism as risk factors for breast cancer. The pre-existing risk factors for breast cancer addressed are benign breast disease, a family history of breast cancer, nulliparity, a late first delivery, and natural menopause.We have developed a model in which the risk increase by HRT use (b) and that by a pre-existing risk factor (c) would be added to the general risk for breast cancer in the normal population (i). The difference in risk with the use of HRT between the risk found in women with a pre-existing risk factor (a + b + c + d) and the risk found in women without a pre-existing risk factor (a + b) is dependent on the typical relative risk increase by the pre-existing risk factor (c) and on a possible risk interaction factor (d). Since the risk increase due to the typical relative risk (c) is known from the literature, the risk interaction factor d may be calculated. Ifd = 0, there is no interaction between HRT and the pre-existing risk factor. With a positive value of d there is synergism between HRT and the pre-existing risk factor.Using data from six recent meta-analyses, we failed to demonstrate a consistent synergistic increase of breast cancer risk with any of the investigated risk factors when HRT is used.