Risk factors for breast cancer for women aged 40 to 49 years: a systematic review and meta-analysis

Ann Intern Med. 2012 May 1;156(9):635-48. doi: 10.7326/0003-4819-156-9-201205010-00006.


Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions.

Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.

Data sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium.

Study selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor.

Data extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means.

Data synthesis: Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk.

Limitations: Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered.

Conclusion: Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening.

Primary funding source: National Cancer Institute.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Biopsy
  • Breast / anatomy & histology
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • Early Detection of Cancer
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Mammography
  • Mass Screening / methods
  • Middle Aged
  • Proportional Hazards Models
  • Reproductive History
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology