Purpose Endogenous hormones are risk factors for postmenopausal breast cancer, and their measurement may improve our ability to identify high-risk women. Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone-binding globulin (SHBG) improved risk prediction for postmenopausal invasive breast cancer (n = 437 patient cases and n = 775 controls not using postmenopausal hormones) in the Nurses'Health Study.
Methods We evaluated improvement in the area under the curve (AUC) for 5-year risk of invasive breast cancer by adding each hormone to the Gail and Rosner-Colditz risk scores. We used stepwise regression to identify the subset of hormones most associated with risk and assessed AUC improvement; we used 10-fold cross validation to assess model overfitting.
Results Each hormone was associated with breast cancer risk (odds ratio doubling, 0.82 [SHBG] to 1.37 [estrone sulfate]). Individual hormones improved the AUC by 1.3 to 5.2 units relative to the Gail score and 0.3 to 2.9 for the Rosner-Colditz score. Estrone sulfate, testosterone, and prolactin were selected by stepwise regression and increased the AUC by 5.9 units (P = .003) for the Gail score and 3.4 (P = .04) for the Rosner-Colditz score. In cross validation, the average AUC change across the validation data sets was 6.0 (P = .002) and 3.0 units (P = .03), respectively. Similar results were observed for estrogen receptor-positive disease (selected hormones: estrone sulfate, testosterone, prolactin, and SHBG; change in AUC, 8.8 [P < .001] for Gail score and 5.8 [P = .004] for Rosner-Colditz score).
Conclusion Our results support that endogenous hormones improve risk prediction for invasive breast cancer and could help identify women who may benefit from chemoprevention or more screening.