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Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk-Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry.

ABSTRACT: The extent to which clinical breast cancer risk prediction models can be improved by including information on known susceptibility SNPs is not known.Using 750 cases and 405 controls from the population-based Australian Breast Cancer Family Registry who were younger than 50 years at diagnosis and recruitment, respectively, Caucasian and not BRCA1 or BRCA2 mutation carriers, we derived absolute 5-year risks of breast cancer using the BOADICEA, BRCAPRO, BCRAT, and IBIS risk prediction models and combined these with a risk score based on 77 independent risk-associated SNPs. We used logistic regression to estimate the OR per adjusted SD for log-transformed age-adjusted 5-year risks. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC). Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. We also constructed reclassification tables and calculated the net reclassification improvement.The ORs for BOADICEA, BRCAPRO, BCRAT, and IBIS were 1.80, 1.75, 1.67, and 1.30, respectively. When combined with the SNP-based score, the corresponding ORs were 1.96, 1.89, 1.80, and 1.52. The corresponding AUCs were 0.66, 0.65, 0.64, and 0.57 for the risk prediction models, and 0.70, 0.69, 0.66, and 0.63 when combined with the SNP-based score.By combining a 77 SNP-based score with clinical models, the AUC for predicting breast cancer before age 50 years improved by >20%.Our estimates of the increased performance of clinical risk prediction models from including genetic information could be used to inform targeted screening and prevention.

SUBMITTER: Dite GS

PROVIDER: S-EPMC4767544 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk-Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry.

Dite Gillian S GS MacInnis Robert J RJ Bickerstaffe Adrian A Dowty James G JG Allman Richard R Apicella Carmel C Milne Roger L RL Tsimiklis Helen H Phillips Kelly-Anne KA Giles Graham G GG Terry Mary Beth MB Southey Melissa C MC Hopper John L JL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20151216 2

<h4>Background</h4>The extent to which clinical breast cancer risk prediction models can be improved by including information on known susceptibility SNPs is not known.<h4>Methods</h4>Using 750 cases and 405 controls from the population-based Australian Breast Cancer Family Registry who were younger than 50 years at diagnosis and recruitment, respectively, Caucasian and not BRCA1 or BRCA2 mutation carriers, we derived absolute 5-year risks of breast cancer using the BOADICEA, BRCAPRO, BCRAT, and ...[more]

PMID: 26677205

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Project description:Background:Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. Objective:To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Design:Collaborative simulation modeling using national incidence, breast density, and screening performance data. Setting:United States. Patients:Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Intervention:Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Measurements:Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted. Results:Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Limitation:Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Conclusion:Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening. Primary Funding Source:National Cancer Institute.

Dataset Information

Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk-Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry.

Publications

Breast Cancer Risk Prediction Using Clinical Models and 77 Independent Risk-Associated SNPs for Women Aged Under 50 Years: Australian Breast Cancer Family Registry.

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