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Cancer Epidemiol Biomarkers Prev. 2020 Mar;29(3):574-581. doi: 10.1158/1055-9965.EPI-19-1120. Epub 2020 Jan 16.

Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer.

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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Analytical Chemistry and Neurochemistry, Department of Chemistry - BMC, Uppsala University, Uppsala, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology, South General Hospital, Stockholm, Sweden.



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.


This study within the KARMA cohort included prediagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (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.


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 (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with 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 with only including density.


DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer.


Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.

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