Posted on March 03, 2000 06:38 AM PST

The relationship between postmenopausal hormone replacement therapy (HRT) and breast cancer remains controversial. Two recent studies suggest that estrogen use is associated with increased risk and that adding progestin to treatment may increase the risk further.

The first study was an analysis of 2082 breast cancers in 46,335 postmenopausal women participating in the National Cancer Institute's Breast Cancer Detection Demonstration Project. Investigators reported increased risk for cancer with estrogen alone (relative risk, 1.2; 95 percent CI, 1.0-1.4) and with estrogen-progestin (RR, 1.4; 95 percent CI, 1.1-1.8) when these agents were used within the 4 years before diagnosis. Among these recent users, the risk increased with each year of use, was significantly greater with estrogen-progestin than with estrogen alone, and was confined to women with body-mass indexes of 24.4 or less. Risk in heavier women did not increase with estrogen or estrogen-progestin. The trends in risk were evident regardless of the type of tumor or the extent of invasive disease.

In the second study, 1897 postmenopausal women with breast cancer were compared with 1637 postmenopausal controls who had not undergone hysterectomies. For each 5-year period of use, HRT was associated with a 10 percent higher risk for cancer. Again, the risk was substantially higher with estrogen-progestin (odds ratio for each 5-year period, 1.24) than with estrogen alone (OR, 1.06). There was a nonsignificant trend toward higher risk with sequential therapy than with continuous administration of estrogen-progestin.

Comment: These findings of increased risk for breast cancer associated with HRT are consistent with those of an earlier meta-analysis (see *JW* 1997 Nov 15, p. 174, accession number 971024001, and *Lancet* 1997; 350:1047). The current studies also reported a slightly greater risk associated with estrogen-progestin use. However, it should be noted that there were markedly fewer estrogen-progestin cases than estrogen-only cases. The data emphasize the need for careful consideration of estrogen use. -- RW Rebar