Abstract
BACKGROUND: The Breast and Ovarian Analysis of Disease Incidence Algorithm (BOADICEA) model predicts breast cancer risk using cancer family history, epidemiological, and genetic data. We evaluated its validity in a large prospective cohort.
METHODS: We assessed model calibration, discrimination and risk classification ability in 217 885 women (6838 incident breast cancers) aged 40-70 years of self-reported White ethnicity with no previous cancer from the UK Biobank. Age-specific risk classification was assessed using relative risk thresholds equivalent to the absolute lifetime risk categories of less than 17%, 17%-30%, and 30% or more, recommended by the National Institute for Health and Care Excellence guidelines. We predicted 10-year risks using BOADICEA v.6 considering cancer family history, questionnaire-based risk factors, a 313-single nucleotide polymorphisms polygenic score, and pathogenic variants. Mammographic density data were not available.
RESULTS: The polygenic risk score was the most discriminative risk factor (area under the curve [AUC] = 0.65). Discrimination was highest when considering all risk factors (AUC = 0.66). The model was well calibrated overall (expected-to-observed ratio = 0.99, 95% confidence interval [CI] = 0.97 to 1.02; calibration slope = 0.99, 95% CI = 0.99 to 1.00), and in deciles of predicted risks. Discrimination was similar in women aged younger and older than 50 years. There was some underprediction in women aged younger than 50 years (expected-to-observed ratio = 0.89, 95% CI = 0.84 to 0.94; calibration slope = 0.96, 95% CI = 0.94 to 0.97), which was explained by the higher breast cancer incidence in UK Biobank than the UK population incidence in this age group. The model classified 87.2%, 11.4%, and 1.4% of women in relative risk categories less than 1.6, 1.6-3.1, and at least 3.1, identifying 25.6% of incident breast cancer patients in category relative risk of at least 1.6.
CONCLUSION: BOADICEA, implemented in CanRisk (www.canrisk.org), provides valid 10-year breast cancer risk, which can facilitate risk-stratified screening and personalized breast cancer risk management.