Therapeutic and Diagnostic Factors as Related to Cancer Risk

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A large part of our portfolio within this Project has focused on the effects on cancer risk of exogenous hormones. Descriptive analyses using data from SEER documented increases in endometrial cancer incidence after 2002 when results from the Womens Health Initiative (WHI) Trial were published. We hypothesized that this reflected widespread decreases in continuous estrogen plus progestin (E+P) MHT use (the therapy linked with increased breast cancer risk within WHI), given that this is an exposure that we as well as others have documented as leading to reductions in endometrial cancer risk in overweight and obese women. In contrast, in another analysis, we found long-term sequential E+P use (which involves substantial exposure to unopposed estrogens) is associated with increased risk; this association was restricted to thin-to-normal weight women, presumably reflecting their lower endogenous estrogen levels. In an additional investigation focused on ovarian cancer, we found that both sequential and continuous E+P usage was associated with ovarian cancer risk increases. In fact, in a descriptive study, we noted an accelerated decline in ovarian cancer incidence among women 50 years and older in age-period-cohort models following the marked reduction in MHT use that occurred after publication of the WHI results. The notable gender discrepancy in rates of liver cancer has suggested that hormones influence risk, leading to an interest in the effects of MHT use. However, in the Liver Cancer Pooling Project (LCPP), we found no evidence that liver cancer risk was related to MHT use, although we had limited information of the specific types of preparations used.In addition to MHT, we have also been concerned regarding the long-term use of fertility drugs. In an extended followup of our large U.S. infertility cohort, we saw no relationship of clomiphene use to either ovarian or endometrial cancers. However, women exposed to 12 or more clomiphene cycles were at an