Effect of hormone replacement therapy on breast cancer risk: Estrogen versus estrogen plus progestin

Background: Hormone replacement therapy (HRT) given as unopposed estrogen r eplacement therapy (ERT) gained widespread popularity in the United States in the 1960s and 1970s. Recent prescribing practices have favored combinati on HRT (CHRT), i.e., adding a progestin to estrogen for the entire monthly cycle (continuous combined replacement therapy [CCRT]) or a part of the cyc le (sequential estrogen plus progestin therapy [SEPRT]). Few data exist on the association between CHRT and breast cancer risk. We determined the effe cts of CHRT on a woman's risk of developing breast cancer in a population-b ased, case-control study, Methods: Case subjects included those with incide nt breast cancers diagnosed over 4 1/2 years in Los Angeles County, CA, in the late 1980s and 1990s, Control subjects were neighborhood residents who were individually matched to case subjects on age and race. Case subjects a nd control subjects were interviewed in person to collect information on kn own breast cancer risk factors as well as on HRT use. Information on 1897 p ostmenopausal case subjects and on 1637 postmenopausal control subjects age d 55-72 Sears who had not undergone a simple hysterectomy was analyzed. Bre ast cancer risks associated with the various types of HRT were estimated as odds ratios (ORs) after adjusting simultaneously for the different forms o f HRT and for known risk factors of breast cancer. All P values are two-sid ed, Results: HRT was associated with a 10% higher breast cancer risk for ea ch 5 years of use (OR5 = 1.10; 95% confidence interval [CI] = 1.02-1.18). R isk 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 high er for SEPRT (OR5 = 1.38; 95% CI = 1.13-1.68) than for CCRT (OR5 = 1.09; 95 % CI = 0.88-1.35), but this difference was not statistically significant. C onclusions: This study provides strong evidence that the addition of a prog estin to HRT enhances markedly the risk of breast cancer relative to estrog en use alone. These findings have important implications for the risk-benef it equation for HRT in women using CHRT.