Falk RT, et al. - Given that the Women's Health Initiative (WHI) found an unexpected reduced breast cancer risk in women using CEE alone, researchers investigated whether this reduction by CEE alone could be attributed to induction of estrogen hydroxylation along the 2-pathway rather than the competing 16-pathway. They examined 1,864 women in a Women's Health Initiative Observational Study (WHIOS) case-control study of estrogen metabolism and ovarian and endometrial cancer. Among those, a total of 609 subjects were current E+P users (351 used CEE+MPA), while 272 used E alone (162 used CEE). Findings suggested a more extensive metabolism via the 2- vs the competing 16-pathway among women using E alone vs E+P users, and this is consistent with epidemiologic evidence of a lower risk of postmenopausal breast cancer linked with this metabolic profile. These data could also shed light on the reduced risk of breast cancer in those using CEE alone during the WHI.