Epidemiological evidence now consistently supports a modest increase in
breast cancer risk among women using postmenopausal
hormones, usually
estrogens. Less is known regarding how the addition of
progestin affects
breast cancer risk. The objective of this study was to investigate the type and duration of postmenopausal
therapy and
breast cancer risk. We performed a multicenter population-based case-control study set in Massachusetts, New Hampshire, and Wisconsin. The subjects were 5298 postmenopausal women (age range, 50-79 years) with a new diagnosis of invasive
breast cancer from statewide
tumor registries. For comparison, 5571 controls were randomly selected from population lists. Participants completed a structured telephone interview covering
hormone use and
breast cancer risk factors. Multivariable regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The RR for
breast cancer increased with longer durations of
hormone use, about 2%/year for
estrogen alone (RR, 1.02; 95% CI, 1.01-1.03) and 4%/year for
estrogen-
progestin use (RR, 1.04; 95% CI, 1.01-1.08).
Estrogen-
progestin use that was both recent and long term (>5 years in duration) was more strongly associated with
breast cancer risk (RR, 1.57; 95% CI, 1.15-2.14) than similar use of
estrogen alone (RR, 1.39; 95% CI, 1.17-1.65). In
estrogen-
progestin users, risks were similar for sequential and continuous use regimens but perhaps stronger for lobular than ductal
breast cancer. Use of
progestin alone was associated with a doubling of risk (RR, 2.09; 95% CI, 1.07-4.07 for ever use versus nonuse).
Estrogen-
progestin use, both sequential and continuous, appears to be more strongly associated with risk of
breast cancer than use of
estrogen alone.