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Inclusion of endogenous plasma dehydroepiandrosterone sulphate and mammographic density in risk prediction models for breast cancer

Gabrielson M1, Ubhayaseker KA2, Acharya SR2, Andersson Franko M3, Eriksson M4, Bergquist J5, Czene K6, Hall P6.

Cancer Epidemiol Biomarkers Prev. 2020 Jan 16. pii: cebp.1120.2019. doi: 10.1158/1055-9965.EPI-19-1120. [Epub ahead of print]

Background Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women.

Methods This study within the KARMA cohort included pre-diagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulphate (DHEAS) and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density, to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score.

Results DHEAS and percentage density were independently and positively associated with breast cancer risk (P=0.007 and P<0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (odds ratio (OR) 3.5; 95% confidence interval (CI) 1.9-6.3) compared to the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P=0.008) and Tyrer-Cuzick (+1.3 units, P=0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units, (P=0.006) and 0.4 units (P=0.007), respectively, compared to only including density. Conclusion DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer. Impact Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualised breast cancer screening and/or preventive measures among postmenopausal women.