Post-menopausal
hormone therapy with
estrogen plus
progestin is consistently reported to be associated with an increased risk of invasive
breast cancer. However, findings on an association between
hormone use and
ductal carcinoma in situ of the breast (
DCIS), a possible precursor lesion of invasive
breast cancer, are sparse and inconsistent. Women's Health Initiative data were used to assess the effects of
hormone therapy on the risk of
DCIS in two clinical trials of
hormone therapy (16,276 women enrolled in the trial of daily
conjugated equine estrogens plus
medroxyprogesterone acetate (CEE + MPA) vs placebo; 10,187 women enrolled in the trial of CEE-alone vs placebo). The effects of
hormone therapy on
DCIS in clinical trial participants were assessed during the intervention, post-intervention, and entire followup periods, and in the observational study (OS; 30,421 CEE + MPA users and non-users and 18,657 CEE-alone users and non-users who met eligibility criteria similar to the clinical trial). Compared to placebo, CEE + MPA was non-significantly associated with higher risk of
DCIS over approximate average of 11 years of follow-up (HR = 1.23; 95 % CI: 0.91-1.64). No statistical difference was detected between intervention and post-intervention phases (p = 0.32). Corresponding OS results supported an increased risk for
DCIS in CEE + MPA users compared to women who were non-users (HR = 1.65; 95 % CI: 1.25-2.19) after adjusting for potential confounders. There was no clear association between CEE-alone use and risk of
DCIS. CEE-alone trial data showed that the risk of
DCIS was non-significantly lower in the treatment than in the placebo group, while analysis of the corresponding OS showed a non-significantly higher risk of
DCIS in the CEE-alone users than non-users. Our analysis suggests that combined
estrogen plus
progestin use in post-menopausal women may increase risk of
DCIS. Whether
estrogen-alone use is associated with
DCIS requires further investigation.