Breast Cancer Risk From Modifiable and Nonmodifiable Risk Factors Among White Women in the United States

Abstract

Importance: An improved model for risk stratification can be useful for guiding public health strategies of breast cancer prevention.

Objective: To evaluate combined risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epidemiologic risk factors.

Design, setting, and participants: Using a total of 17 171 cases and 19 862 controls sampled from the Breast and Prostate Cancer Cohort Consortium (BPC3) and 5879 women participating in the 2010 National Health Interview Survey, a model for predicting absolute risk of breast cancer was developed combining information on individual level data on epidemiologic risk factors and 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, population incidence rate from the National Cancer Institute-Surveillance, Epidemiology, and End Results Program cancer registry and data on risk factor distribution from nationally representative health survey. The model is used to project the distribution of absolute risk for the population of white women in the United States after adjustment for competing cause of mortality.

Exposures: Single nucleotide polymorphisms, family history, anthropometric factors, menstrual and/or reproductive factors, and lifestyle factors.

Main outcomes and measures: Degree of stratification of absolute risk owing to nonmodifiable (SNPs, family history, height, and some components of menstrual and/or reproductive history) and modifiable factors (body mass index [BMI; calculated as weight in kilograms divided by height in meters squared], menopausal hormone therapy [MHT], alcohol, and smoking).

Results: The average absolute risk for a 30-year-old white woman in the United States developing invasive breast cancer by age 80 years is 11.3%. A model that includes all risk factors provided a range of average absolute risk from 4.4% to 23.5% for women in the bottom and top deciles of the risk distribution, respectively. For women who were at the lowest and highest deciles of nonmodifiable risks, the 5th and 95th percentile range of the risk distribution associated with 4 modifiable factors was 2.9% to 5.0% and 15.5% to 25.0%, respectively. For women in the highest decile of risk owing to nonmodifiable factors, those who had low BMI, did not drink or smoke, and did not use MHT had risks comparable to an average woman in the general population.

Conclusions and relevance: This model for absolute risk of breast cancer including SNPs can provide stratification for the population of white women in the United States. The model can also identify subsets of the population at an elevated risk that would benefit most from risk-reduction strategies based on altering modifiable factors. The effectiveness of this model for individual risk communication needs further investigation.

Figure 1. Projected Distribution of Absolute Lifetime Risk of Breast Cancer for White Women in the United States Ages 30 to 80 Years

SNP indicates single nucleotide polymorphisms.

Figure 2. Cumulative and 10-Year Breast Cancer Risk for White Women in the United States Stratified by Risk Percentiles

Cumulative risk is evaluated as absolute risk between age 30 years and a specific age shown on the x-axis. The 10-year risk is evaluated as absolute risk over the next 10 years for a woman who has attained a specific age (shown on the x-axis) without developing breast cancer.

Figure 3. Distribution of Absolute Lifetime Risk Associated With Modifiable Risk Factors Stratified by Deciles of Nonmodifiable Risk for White Women in the United States

The horizontal line in the middle of each box indicates the median, while the top and bottom borders of the box mark the 75th and 25th percentiles, respectively. The whiskers above and below the box are the minimum and maximum excluding outliers; outliers were defined as individuals who had risk beyond above or below a standard deviation of 3 of means in the log-scale. Lifetime risk refers to cumulative risk between age 30 to 80 years. The dashed line indicates average lifetime risk for the population.