Effects of estrogens and hormone replacement therapy on breast cancer riskand on efficacy of breast cancer therapies

This review summarises preclinical and clinical data on effects of endogeno us and exogenous estrogens on probability of breast cancer diagnosis, and o n the course and efficacy of breast cancer therapies. The data indicate tha t higher endogenous estrogen exposure (e.g. pregnancy, early menarche and l ate menopause, estrogen levels in future breast cancer patients, obesity) o r exogenous estrogens (oral contraceptives; hormone replacement therapies) may be associated with an increased probability of breast cancer diagnosis. However, there is little evidence that estrogens have deleterious effects on the course of breast cancer. Moreover, increased incidence of breast can cer diagnosis after prolonged hormone replacement therapy (HRT) use seems t o be associated with clinically less advanced disease. In studies assessing both diagnosis and mortality, HRT is frequently associated with reduced mo rtality compared to never users. The interaction of progestagens and estrog ens on the probability of breast cancer diagnosis is complex and dependent on type of progestagens and regimens employed. Efficacy of current treatmen t modalities for breast cancer (surgery, irradiation, adjuvant therapy or c hemotherapy) is not negatively influenced by estrogens at concentrations co nsiderably higher than those attained with current HRT preparations. Althou gh it cannot be excluded that estrogens increase the probability of breast cancer diagnosis, available data fail to demonstrate that, once breast canc er has been diagnosed, estrogens worsen prognosis, accelerate the course of the disease, reduce survival or interfere with the management of breast ca ncer. It may therefore be concluded that the prevalent opinion that estroge ns and estrogen treatment are deleterious for breast cancer, needs to be re visited. However, results of ongoing prospective, randomised clinical trial s with different HRT regimens in healthy women or breast cancer survivors a re needed to provide more definite conclusions about risks and benefits of HRT. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.