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Erschienen in: Breast Cancer Research and Treatment 2/2017

08.08.2017 | Epidemiology

Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones

verfasst von: Yiwey Shieh, Donglei Hu, Lin Ma, Scott Huntsman, Charlotte C. Gard, Jessica W. T. Leung, Jeffrey A. Tice, Elad Ziv, Karla Kerlikowske, Steven R. Cummings

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

Background

Models that predict the risk of estrogen receptor (ER)-positive breast cancers may improve our ability to target chemoprevention. We investigated the contributions of sex hormones to the discrimination of the Breast Cancer Surveillance Consortium (BCSC) risk model and a polygenic risk score comprised of 83 single nucleotide polymorphisms.

Methods

We conducted a nested case-control study of 110 women with ER-positive breast cancers and 214 matched controls within a mammography screening cohort. Participants were postmenopausal and not on hormonal therapy. The associations of estradiol, estrone, testosterone, and sex hormone binding globulin with ER-positive breast cancer were evaluated using conditional logistic regression. We assessed the individual and combined discrimination of estradiol, the BCSC risk score, and polygenic risk score using the area under the receiver operating characteristic curve (AUROC).

Results

Of the sex hormones assessed, estradiol (OR 3.64, 95% CI 1.64–8.06 for top vs bottom quartile), and to a lesser degree estrone, was most strongly associated with ER-positive breast cancer in unadjusted analysis. The BCSC risk score (OR 1.32, 95% CI 1.00–1.75 per 1% increase) and polygenic risk score (OR 1.58, 95% CI 1.06–2.36 per standard deviation) were also associated with ER-positive cancers. A model containing the BCSC risk score, polygenic risk score, and estradiol levels showed good discrimination for ER-positive cancers (AUROC 0.72, 95% CI 0.65–0.79), representing a significant improvement over the BCSC risk score (AUROC 0.58, 95% CI 0.50–0.65).

Conclusion

Adding estradiol and a polygenic risk score to a clinical risk model improves discrimination for postmenopausal ER-positive breast cancers.
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Metadaten
Titel
Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones
verfasst von
Yiwey Shieh
Donglei Hu
Lin Ma
Scott Huntsman
Charlotte C. Gard
Jessica W. T. Leung
Jeffrey A. Tice
Elad Ziv
Karla Kerlikowske
Steven R. Cummings
Publikationsdatum
08.08.2017
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4430-2

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