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Original Research |

Identifying Women With Dense Breasts at High Risk for Interval Cancer: A Cohort StudyIdentifying Women With Dense Breasts at High Risk for Interval Cancer

Karla Kerlikowske, MD; Weiwei Zhu, MS; Anna N.A. Tosteson, ScD; Brian L. Sprague, PhD; Jeffrey A. Tice, MD; Constance D. Lehman, MD, PhD; Diana L. Miglioretti, PhD, for the Breast Cancer Surveillance Consortium*
[+] Article, Author, and Disclosure Information

* For a list of Breast Cancer Surveillance Consortium investigators, see the Appendix.


From the University of California, San Francisco, San Francisco, California; Group Health Cooperative and University of Washington School of Medicine, Seattle, Washington; Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire; University of Vermont, Burlington, Vermont; and University of California, Davis, Davis, California.

Acknowledgment: The authors thank the participating women, mammography facilities, and radiologists for the data they provided for this study. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes are provided at http://breastscreening.cancer.gov.

Grant Support: This work was supported by the National Cancer Institute–funded BCSC (P01 CA154292, HHSN261201100031C, and U54 CA163303). The collection of cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. A full description of these sources is available at http://breastscreening.cancer.gov/work/acknowledgement.html.

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1465.

Reproducible Research Statement:Study protocol and statistical code: Available from the BCSC's statistical coordinating center (e-mail, SCC@ghc.org). Data set: Available with approval of the BCSC Steering Committee (http://breastscreening.cancer.gov).

Requests for Single Reprints: Karla Kerlikowske, MD, San Francisco Veterans Affairs Medical Center, General Internal Medicine Section, 111A1, 4150 Clement Street, San Francisco, CA 94121.

Current Author Addresses: Dr. Kerlikowske: San Francisco Veterans Affairs Medical Center, General Internal Medicine Section, 111A1, 4150 Clement Street, San Francisco, CA 94121.

Ms. Zhu: Group Health Research Institute, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101.

Dr. Tosteson: Geisel School of Medicine at Dartmouth, One Medical Center Drive (HB7505), Lebanon, NH 03756.

Dr. Sprague: Office of Health Promotion Research, 1 South Prospect Street, Burlington, VT 05446.

Dr. Tice: Associate Professor of Medicine, University of California, San Francisco, 1545 Divisadero, 309, San Francisco, CA 94143-0320.

Dr. Lehman: University of Washington, Seattle Cancer Care Alliance, 825 Eastlake Avenue East, G2-600, Seattle, WA 98109.

Dr. Miglioretti: UC Davis School of Medicine, Department of Public Health Sciences, One Shields Avenue, Med Sci 1C, Room 145, Davis, CA 95616.

Author Contributions: Conception and design: K. Kerlikowske, B.L. Sprague, D.L. Miglioretti.

Analysis and interpretation of the data: K. Kerlikowske, W. Zhu, A.N.A. Tosteson, B.L. Sprague, J.A. Tice, C.D. Lehman, D.L. Miglioretti.

Drafting of the article: K. Kerlikowske.

Critical revision of the article for important intellectual content: K. Kerlikowske, A.N.A. Tosteson, B.L. Sprague, J.A. Tice, C.D. Lehman, D.L. Miglioretti.

Final approval of the article: K. Kerlikowske, W. Zhu, A.N.A. Tosteson, B.L. Sprague, J.A. Tice, C.D. Lehman, D.L. Miglioretti.

Provision of study materials or patients: K. Kerlikowske.

Statistical expertise: K. Kerlikowske, W. Zhu, D.L. Miglioretti.

Obtaining of funding: K. Kerlikowske, A.N.A. Tosteson, B.L. Sprague, D.L. Miglioretti.

Administrative, technical, or logistic support: K. Kerlikowske.

Collection and assembly of data: K. Kerlikowske, W. Zhu, B.L. Sprague, D.L. Miglioretti.


Ann Intern Med. 2015;162(10):673-681. doi:10.7326/M14-1465
Text Size: A A A

Background: Twenty-one states have laws requiring that women be notified if they have dense breasts and that they be advised to discuss supplemental imaging with their provider.

Objective: To better direct discussions of supplemental imaging by determining which combinations of breast cancer risk and Breast Imaging Reporting and Data System (BI-RADS) breast density categories are associated with high interval cancer rates.

Design: Prospective cohort.

Setting: Breast Cancer Surveillance Consortium (BCSC) breast imaging facilities.

Patients: 365 426 women aged 40 to 74 years who had 831 455 digital screening mammography examinations.

Measurements: BI-RADS breast density, BCSC 5-year breast cancer risk, and interval cancer rate (invasive cancer ≤12 months after a normal mammography result) per 1000 mammography examinations. High interval cancer rate was defined as more than 1 case per 1000 examinations.

Results: High interval cancer rates were observed for women with 5-year risk of 1.67% or greater and extremely dense breasts or 5-year risk of 2.50% or greater and heterogeneously dense breasts (24% of all women with dense breasts). The interval rate of advanced-stage disease was highest (>0.4 case per 1000 examinations) among women with 5-year risk of 2.50% or greater and heterogeneously or extremely dense breasts (21% of all women with dense breasts). Five-year risk was low to average (0% to 1.66%) for 51.0% of women with heterogeneously dense breasts and 52.5% with extremely dense breasts, with interval cancer rates of 0.58 to 0.63 and 0.72 to 0.89 case per 1000 examinations, respectively.

Limitation: The benefit of supplemental imaging was not assessed.

Conclusion: Breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies.

Primary Funding Source: National Cancer Institute.

Figures

Grahic Jump Location
Figure.

Study flow diagram.

* Includes 1079 women with ductal carcinoma in situ.

† Mammography not associated with invasive cancer diagnosis ≤12 mo after examination and occurring >9 mo before mammography associated with invasive cancer diagnosis.

Grahic Jump Location

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Summary for Patients

Identifying Women With Dense Breasts at High Risk for Interval Cancer

The full report is titled “Identifying Women With Dense Breasts at High Risk for Interval Cancer. A Cohort Study.” It is in the 19 May 2015 issue of Annals of Internal Medicine (volume 162, pages 673-681). The authors are K. Kerlikowske, W. Zhu, A.N.A. Tosteson, B.L. Sprague, J.A. Tice, C.D. Lehman, and D.L. Miglioretti, for the Breast Cancer Surveillance Consortium.

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