Epidemiologic analysis of breast and gynecologic cancers.Prog Clin Biol Res 1997; 396:17-29PC
This review focuses on etiologic factors and hormonal correlates of the three major gynecologic cancers-uterine cervix, uterine corpus and ovary- and breast cancer. The incidence rate of the three gynecologic cancers combined is only 40 percent of the breast cancer rate (43.6 vs 109.5 per 100,000), whereas the combined mortality rate is half that for breast cancer (14.3 vs 27.3 per 100,000). Cervical cancer is distinctive in that it's hormonal correlates are few; it exhibits the epidemiologic characteristics of a sexually transmitted disease. Integration of Human Papilloma Virus DNA types 16, 18 (or other) within the cellular genome has been identified in more than 80% of high grade cervical intraepithelial neoplasias and invasive carcinomas. Epithelial ovarian cancers occur most commonly in nulliparous, infertile women and familial carriers of BRCA1. Oral contraceptive (OC) use reduces ovarian cancer risk by at least one-half, a benefit which increases with increasing duration of use and persists for at least 15 years after discontinuation. Pregnancy and OCs suppress gonadotropin secretion, whereas fertility drugs enhance follicle-stimulating hormone production. These indicators of alterations in the hypothalmic-pituitary-ovarian axis provide some support for both the excess gonadotropin and the incessant ovulation theories of ovarian carcinogenesis. Endometrial carcinoma is the prototype hormonally-determined disease. Increased estrogen from either endogenous or exogenous sources increases risk. Lowering the estrogen load or adding progestin reduces risk. This explains the marked protection achieved by combined estrogen/progestin OC's and the dramatic increased risk uncurred by long-term estrogen replacement therapy (ERT). Breast tissue, also a target for sex steroid hormones, displays a more complex risk profile. Current ERT use increases breast cancer risk by about 30%; adding a progestin to the estrogen does not improve the situation (40% increased risk). Furthermore, OCs do not reduce breast cancer risk, but may increase it for current OC users under age 45. The magnitude of these hormonal effects is much smaller than that exhibited with endometrial cancer.