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- Title
Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model.
- Authors
Clendenen, Tess V.; Ge, Wenzhen; Koenig, Karen L.; Afanasyeva, Yelena; Agnoli, Claudia; Brinton, Louise A.; Darvishian, Farbod; Dorgan, Joanne F.; Eliassen, A. Heather; Falk, Roni T.; Hallmans, Göran; Hankinson, Susan E.; Hoffman-Bolton, Judith; Key, Timothy J.; Krogh, Vittorio; Nichols, Hazel B.; Sandler, Dale P.; Schoemaker, Minouk J.; Sluss, Patrick M.; Sund, Malin
- Abstract
<bold>Background: </bold>Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.<bold>Methods: </bold>In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.<bold>Results: </bold>The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.<bold>Conclusions: </bold>AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
- Subjects
BREAST cancer
- Publication
Breast Cancer Research, 2019, Vol 21, Issue 1, pN.PAG
- ISSN
1465-5411
- Publication type
journal article
- DOI
10.1186/s13058-019-1126-z