Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model

Using Clinical Factors and Mammographic Breast Density to Estimate Breast Cancer Risk: Development and Validation of a New Predictive Model

From University of California, San Francisco, San Francisco, California, and Cancer Research and Biostatistics and University of Washington, Seattle, Washington.

Abstract

Background: Current models for assessing breast cancer risk are complex and do not include breast density, a strong risk factor for breast cancer that is routinely reported with mammography.

Objective: To develop and validate an easy-to-use breast cancer risk prediction model that includes breast density.

Design: Empirical model based on Surveillance, Epidemiology, and End Results incidence, and relative hazards from a prospective cohort.

Setting: Screening mammography sites participating in the Breast Cancer Surveillance Consortium.

Patients: 1 095 484 women undergoing mammography who had no previous diagnosis of breast cancer.

Measurements: Self-reported age, race or ethnicity, family history of breast cancer, and history of breast biopsy. Community radiologists rated breast density by using 4 Breast Imaging Reporting and Data System categories.

Results: During 5.3 years of follow-up, invasive breast cancer was diagnosed in 14 766 women. The breast density model was well calibrated overall (expected–observed ratio, 1.03 [95% CI, 0.99 to 1.06]) and in racial and ethnic subgroups. It had modest discriminatory accuracy (concordance index, 0.66 [CI, 0.65 to 0.67]). Women with low-density mammograms had 5-year risks less than 1.67% unless they had a family history of breast cancer and were older than age 65 years.

Limitation: The model has only modest ability to discriminate between women who will develop breast cancer and those who will not.

Conclusion: A breast cancer prediction model that incorporates routinely reported measures of breast density can estimate 5-year risk for invasive breast cancer. Its accuracy needs to be further evaluated in independent populations before it can be recommended for clinical use.

Article and Author Information

Acknowledgment: The authors thank the BCSC investigators, participating mammography facilities, and radiologists for the data they provided for the study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are available at http://breastscreening.cancer.gov/.
Grant Support: By the National Cancer Institute–funded Breast Cancer Surveillance Consortium cooperative agreement (grants U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040) and a Building Interdisciplinary Research Careers in Women's Health faculty development grant (K12 AR47659).
Potential Financial Conflicts of Interest:Consultancies: S.R. Cummings (Eli Lilly). Honoraria: S.R. Cummings (Eli Lilly).
Grants received: J.A. Tice (Building Interdisciplinary Careers in Women's Health [career development award]), S.R. Cummings (Eli Lilly, Lilly Foundation). Grants pending: S.R. Cummings (Eli Lilly, Lilly Foundation).
Reproducible Research Statement: The data set is available through the BCSC Web site (available at http://breastscreening.cancer.gov/).
Requests for Single Reprints: Jeffrey A. Tice, MD, Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, 1701 Divisadero Street, Suite 554, San Francisco, CA 94143-1732; e-mail, jtice{at}medicine.ucsf.edu.
Current Author Addresses: Dr. Tice: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, 1701 Divisadero Street, Suite 554, San Francisco, CA 94143-1732.
Dr. Cummings: San Francisco Coordinating Center, 185 Berry Street, Lobby 4, Suite 5700, San Francisco, CA 94107.
Dr. Smith-Bindman: University of California, San Francisco, 185 Berry Street, Suite 350, San Francisco, CA 94143.
Ms. Ichikawa: The Center for Health Studies, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.
Dr. Barlow: Cancer Research and Biostatistics, 1730 Minor Avenue, Suite 1900, Seattle, WA 98101.
Dr. Kerlikowske: University of California, San Francisco, 4150 Clement Street, San Francisco, CA 94121.
Author Contributions: Conception and design: J.A. Tice, S.R. Cummings, W.E. Barlow, K. Kerlikowske.
Analysis and interpretation of the data: J.A. Tice, S.R. Cummings, W.E. Barlow, K. Kerlikowske.
Drafting of the article: J.A. Tice, K. Kerlikowske.
Critical revision of the article for important intellectual content: J.A. Tice, S.R. Cummings, L. Ichikawa, K. Kerlikowske.
Final approval of the article: J.A. Tice, S.R. Cummings, L. Ichikawa, W.E. Barlow, K. Kerlikowske.
Provision of study materials or patients: K. Kerlikowske.
Statistical expertise: J.A. Tice, W.E. Barlow.
Obtaining of funding: J.A. Tice, W.E. Barlow, K. Kerlikowske.
Administrative, technical, or logistic support: S.R. Cummings, K. Kerlikowske.
Collection and assembly of data: L. Ichikawa, W.E. Barlow, K. Kerlikowske.