Breast cancer: hormones and other risk factors

In North America and Northern Europe, breast cancer incidence rates begin i ncreasing in the early reproductive years and continue climbing into the la te seventies, whereas rates plateau after menopause in japan and less devel oped countries. Female gender, age and country of birth are the strongest d eterminants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphism s associated with estrogen synthesis and metabolism are currently under stu dy. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In post-m enopausal women, increased breast density on mammograms increases risk. Bon e density and breast cancer are associated, presumably through the mechanis m of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cance r may function through and endocrine mechanism. Current use of oral contrac eptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relations hips between various dietary micro and macronutrients and breast cancer hav e been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. C onclusion: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interacti on of these genes with steroid hormones: and relevant growth factors. This knowledge should be useful for breast cancer prevention. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.