Breast Cancer Research and Treatment

, Volume 149, Issue 3, pp 569–575 | Cite as

Breast cancer risk associated with benign breast disease: systematic review and meta-analysis

  • Sara W. DyrstadEmail author
  • Yan Yan
  • Amy M. Fowler
  • Graham A. Colditz


Benign breast disease (BBD) is a broad category of diagnoses reported to convey a variable degree of increased risk of developing breast cancer. A meta-analysis of the existing literature was performed to quantify the risk estimate associated with BBD. Pubmed, Google Scholar, and EMBASE databases were searched in January 2011. English retrospective and prospective observational studies published from 1972 to 2010 evaluating BBD and the risk of breast cancer were included with data acquisition reported from 1930 to 2007. Eligibility was performed independently following a standardized protocol for full-text publication review by a single reviewer and reviewed by a second author. Of the 3,409 articles retrieved from the literature search, 32 studies met the selection criteria. Reported risk estimates, including relative risk, odds ratio, standardized incidence ratios, rate ratio, hazards ratio, and incidence rate ratio, were the primary outcomes extracted. The most commonly reported pathologies were decided prior to extraction and organized into the following categories for analysis of the extracted risk estimate: non-proliferative disease (NPD), proliferative disease without atypia, benign breast disease not otherwise specified (BBD), and atypical hyperplasia not otherwise specified (AHNOS). The mean age at benign breast biopsy was 46.1 years and the mean age of developing breast cancer was 55.9 years. The mean follow-up length was 12.8 years (range 3.3–20.6). The summary risk estimate of developing breast cancer for NPD was 1.17 (N = 8; 95 % CI 0.94–1.47). Proliferative disease without atypia was associated with significantly increased risk of future breast cancer, summary relative risk 1.76 (N = 15; 95 % CI 1.58–1.95). The summary risk estimate for AHNOS was 3.93 (N = 13; 95 % CI 3.24–4.76). This meta-analysis demonstrates that proliferative benign breast disease with or without atypia is associated with a significant increase in risk of developing breast cancer. These data support management strategies for women with benign breast disease such as additional screening methods or chemoprevention.


Benign breast disease Breast cancer Atypia Meta-analysis 



Sara W. Dyrstad, MD has full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest

The authors declare that they have no conflict of interest.


NCI P30CA091842, the Breast Cancer Research Foundation, and the Foundation for Barnes-Jewish Hospital. GAC is supported by an ACS Clinical Research Professorship.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Sara W. Dyrstad
    • 1
    • 2
    Email author
  • Yan Yan
    • 3
  • Amy M. Fowler
    • 1
    • 4
  • Graham A. Colditz
    • 3
  1. 1.Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. LouisUSA
  2. 2.Odessa Regional Medical CenterOdessaUSA
  3. 3.Division of Public Health Sciences, Department of SurgeryWashington University School of MedicineSt. LouisUSA
  4. 4.University of Wisconsin in MadisonMadisonUSA

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