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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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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Abbreviations

AUROC:

Area under the receiver operating characteristic curve

BCSC:

Breast Cancer Surveillance Consortium

BI-RADS:

Breast Imaging Reporting and Data System

BMI:

Body mass index

CCR:

California Cancer Registry

CPMC:

California Pacific Medical Center

GWAS:

Genome-wide association study

LR:

Likelihood ratio

OR:

Odds ratio

PRS:

Polygenic risk score

SFMR:

San Francisco Mammography Registry

SHBG:

Sex hormone binding globulin

SNPs:

Single nucleotide polymorphisms

USPSTF:

United States Preventive Services Task Force

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Acknowledgements

We are grateful to Charles E. McCulloch, PhD for his input on statistical methods. The collection of cancer data was supported in part by the California Cancer Registry. For a full description, please see: http://breastscreening.cancer.gov/work/acknowledgement.html. We thank the participating women, mammography facilities, and radiologists for the data they have provided for this study.

Funding

This work was supported by the NCI-funded Breast Cancer Surveillance Consortium grant P01 CA154292. E. Ziv also received support from the National Cancer Institute under grant K24 CA169004. S.R. Cummings also received support for the collection of blood specimens from the DaCosta Fund for the Prevention of Breast Cancer, the Clinical Research in Clinical Care (CRCLE) funds provided by the California Pacific Medical Center, and by a grant from the Eli Lilly Foundation. Y. Shieh was supported by a National Research Service Award through the National Institutes of Health T32 HP19025. Data collection for this work was supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium (HHSN261201100031C). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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Authors and Affiliations

  1. Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94115, USA

    Yiwey Shieh, Donglei Hu, Scott Huntsman, Jeffrey A. Tice & Elad Ziv

  2. University of California, San Francisco, Box 1793, 550 16th Street, San Francisco, CA, 94158, USA

    Lin Ma

  3. Department of Economics, Applied Statistics, and International Business, New Mexico State University, MSC 3CQ, P.O. Box 30001, Las Cruces, NM, 88003, USA

    Charlotte C. Gard

  4. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1350, Houston, TX, 77030, USA

    Jessica W. T. Leung

  5. Department of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA

    Karla Kerlikowske

  6. General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, 4150 Clement St, Mailing Code 111A1, San Francisco, CA, 94121, USA

    Karla Kerlikowske

  7. San Francisco Coordinating Center, California Pacific Medical Center Research Institute, Box 0560, 550 16th Street, 2nd Floor, San Francisco, CA, 94159, USA

    Steven R. Cummings

Authors
  1. Yiwey Shieh
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  2. Donglei Hu
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  3. Lin Ma
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  4. Scott Huntsman
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  5. Charlotte C. Gard
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  6. Jessica W. T. Leung
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  7. Jeffrey A. Tice
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  8. Elad Ziv
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  9. Karla Kerlikowske
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  10. Steven R. Cummings
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Corresponding author

Correspondence to Yiwey Shieh.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Specifically, each registry in the Breast Cancer Surveillance Consortium and the Statistical Coordinating Center (SCC) have received institutional review board approval for either active or passive consenting processes or a waiver of consent to enroll participants, link data, and perform analytic studies. All procedures are Health Insurance Portability and Accountability Act (HIPAA) compliant and all registries and the SCC have received a Federal Certificate of Confidentiality and other protection for the identities of women, physicians, and facilities who are subjects of this research.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Shieh, Y., Hu, D., Ma, L. et al. Joint relative risks for estrogen receptor-positive breast cancer from a clinical model, polygenic risk score, and sex hormones. Breast Cancer Res Treat 166, 603–612 (2017). https://doi.org/10.1007/s10549-017-4430-2

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  • DOI: https://doi.org/10.1007/s10549-017-4430-2

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