Family history and risk of breast cancer: an analysis accounting for family structure

Purpose Family history is an important risk factor for breast cancer incidence, but the parameters conventionally used to categorize it are based solely on numbers and/or ages of breast cancer cases in the family and take no account of the size and age-structure of the woman's family. Methods Using data from the Generations Study, a cohort of over 113,000 women from the general UK population, we analyzed breast cancer risk in relation to first-degree family history using a family history score (FHS) that takes account of the expected number of family cases based on the family's age-structure and national cancer incidence rates. Result Breast cancer risk increased significantly (P (trend) < 0.0001) with greater FHS. There was a 3.5-fold (95% CI 2.56-4.79) range of risk between the lowest and highest FHS groups, whereas women who had two or more relatives with breast cancer, the strongest conventional familial risk factor, had a 2.5-fold (95% CI 1.83-3.47) increase in risk. Using likelihood ratio tests, the best model for determining breast cancer risk due to family history was that combining FHS and age of relative at diagnosis. Conclusion A family history score based on expected as well as observed breast cancers in a family can give greater risk discrimination on breast cancer incidence than conventional parameters based solely on cases in affected relatives. Our modeling suggests that a yet stronger predictor of risk might be a combination of this score and age at diagnosis in relatives.