Benign breast disease, mammographic breast density, and the risk of breast cancer

Jeffrey A. Tice, Ellen S. O'Meara, Donald L. Weaver, Celine Vachon, Rachel Ballard-Barbash, Karla Kerlikowske

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Background Benign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk. Methods We included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided. Results Benign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P <. 001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P =. 003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P <. 001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P <. 001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses. Conclusions Women with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.

Original languageEnglish (US)
Pages (from-to)1043-1049
Number of pages7
JournalJournal of the National Cancer Institute
Issue number14
StatePublished - Jul 17 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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