Background: The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma.

Methods: A large, multicenter case-control study of Caucasian and African-American women who were diagnosed at age < 65 years with their first invasive breast tumor from July 1, 1994 through April 30, 1998 was conducted. In-person interviews were conducted with 1749 postmenopausal patients, and their responses were compared with the responses of 1953 postmenopausal control women identified through random-digit dialing who met the study criteria of being postmenopausal at the time of diagnosis. Polytomous logistic regression was used to calculate the odds ratio (OR) as an estimate of the relative risk and to compute the 95% confidence interval (95%CI) associated with the use of various regimens of hormone replacement therapy (HRT) among women diagnosed with ductal breast carcinoma, lobular (or mixed lobular and ductal) breast carcinoma, and a grouping of other histologic types of breast carcinoma.

Results: Ever use of unopposed estrogen therapy (ERT) was not associated with an increase in the risk of any histologic type of breast carcinoma. The risk of invasive lobular breast carcinoma and the risk of breast carcinoma of the grouping of other histologies increased among women currently using CHRT (OR, 2.2; 95%CI, 1.4-3.3; and OR, 1.9; 95%CI, 1.0-3.4, respectively). The risk increase was greater for the mixed lobular-ductal type than for the pure lobular type of breast carcinoma, although the difference was not statistically significant. There was some indication that >or= 5 years of continuous CHRT (>or= 25 days per month of progestin) was associated with a higher risk of lobular breast carcinoma (OR, 2.5; 95%CI, 1.4-4.3) compared with sequential CHRT (< 25 days per month of progestin; OR, 1.5; 95%CI, 0.8-2.6). Current use of continuous CHRT was only moderately associated with risk of ductal breast carcinoma.

Conclusions: Postmenopausal women who take CHRT appear to be at an increased risk of lobular breast carcinoma. Data from this study suggest that neither ERT use nor CHRT substantially increase the risk of ductal breast carcinoma among women age < 65 years.