Effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin. J Natl Cancer Inst 2000;92:328–32

therapy (HRT) given as unopposed es-trogen replacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have fa-vored combination HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous com-bined replacement therapy [CCRT]) or a part of the cycle (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We de-termined the effects of CHRT on a woman’s risk of developing breast can-cer in a population-based, case–control study. Methods: Case subjects included those with incident breast cancers diag-nosed over 41⁄2 years in Los Angeles County, CA, in the late 1980s and 1990s. Control subjects were neighbor-hood residents who were individually matched to case subjects on age and race. Case subjects and control subjects were interviewed in person to collect information on known breast cancer risk factors as well as on HRT use. In-formation on 1897 postmenopausal case subjects and on 1637 postmeno-pausal control subjects aged 55–72 years who had not undergone a simple hysterectomy was analyzed. Breast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simulta-neously for the different forms of HRT and for known risk factors of breast cancer. All P values are two-sided. Re-sults: HRT was associated with a 10% higher breast cancer risk for each 5 years of use (OR5 = 1.10; 95 % confi-dence interval [CI] = 1.02–1.18). Risk was substantially higher for CHRT use (OR5 = 1.24; 95 % CI = 1.07–1.45) than for ERT use (OR5 = 1.06; 95 % CI = 0.97–1.15). Risk estimates were highe