Abstract
PurposeFamily 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.MethodsUsing 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.ResultsBreast cancer risk increased significantly (Ptrend < 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.ConclusionsA 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.
Highlights
Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide [1]
There was a 3.5-fold range of risk between the lowest and highest family history score (FHS) groups, whereas women who had two or more relatives with breast cancer, the strongest conventional familial risk factor, had a 2.5-fold increase in risk
The best model for determining breast cancer risk due to family history was that combining FHS and age of relative at diagnosis
Summary
Breast cancer is the most common cancer in women and the leading cause of cancer-related deaths in women worldwide [1]. In assessing risk of breast cancer, the categorization of family history as a risk factor for breast cancer has ranged from presence or absence of a family history [5,6,7,8,9,10,11,12,13] to more specific descriptions of cases in the family such as the number, type, age at diagnosis (e.g., B45 or [45 [14, 15], or B50 or [50 years [11, 14, 16]) of relatives who have had breast cancer [16,17,18,19,20,21,22,23,24,25], and a combination of the type of relative and age at diagnosis [3, 26] These methods did not consider, the number of female relatives, and the person-years they have lived through, by age and calendar period, i.e., the denominator of the family’s risk. We used data from the Generations Study, a cohort study of women in the UK, to analyze breast cancer incidence risks in relation to a family history score that takes account of the person-years at risk by age and calendar period, and the relatives’ ages at breast cancer incidence, and the numbers of breast cancers expected in the family
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