Tosteson, Anna N.A.

10500 Background: Inherited pathogenic variants in ATM, CHEK2, and PALB2 confer moderate to high risks of breast cancer. The optimal approach to screening in these women has not been established. Methods: We used two simulation models from the Cancer Intervention and Surveillance Modeling Network (CISNET) and data from the Cancer Risk Estimates Related to Susceptibility consortium (CARRIERS) to project lifetime breast cancer incidence and mortality in ATM, CHEK2, and PALB2 carriers. We simulated screening with annual mammography from ages 40-74 alone and with annual magnetic resonance imaging (MRI) starting at ages 40, 35, 30, and 25. Joint and separate mammography and MRI screening performance was based on published literature. Lifetime outcomes per 1,000 women were reported as means and ranges across both models. Results: Estimated risk of breast cancer by age 80 was 22% (21-23%) for ATM, 28% (26-30%) for CHEK2, and 40% (38-42%) for PALB2. Screening with MRI and mammography reduced breast cancer mortality by 52-60% across variants (Table). Compared to no screening, starting MRI at age 30 increased life years (LY)/1000 women by 501 (478-523) in ATM, 620 (587-652) in CHEK2, and 1,025 (998-1,051) in PALB2. Starting MRI at age 25 versus 30 gained 9-12 LY/1000 women with 517-518 additional false positive screens and 197-198 benign biopsies. Conclusions: For women with ATM, CHEK2, and PALB2 pathogenic variants, breast cancer screening with MRI and mammography halves breast cancer mortality. These mortality benefits are similar to those for MRI screening for BRCA1/2 mutation carriers and should inform practice guidelines.[Table: see text]

Background. Patients’ values are fundamental to decision models, cost-effectiveness analyses, and pharmacoeconomic analyses. The standard methods used to assess how patients value different health states are inherently quantitative. People without strong quantitative skills (i.e., low numeracy) may not be able to complete these tasks in a meaningful way. Methods. To determine whether the validity of utility assessments depends on the respondent’s level of numeracy, the authors conducted in-person interviews and written surveys and assessed utility for the current health for 96 women volunteers. Numeracy was measured using a previously validated 3-item scale. The authors examined the correlation between self-reported health and utility for current health (assessed using the standard gamble, time trade-off, and visual analog techniques) across levels of numeracy. For half of the women, the authors also assessed standard gamble utility for 3 imagined health states (breast cancer, heart disease, and osteoporosis) and asked how much the women feared each disease. Results. Respondent ages ranged from 50 to 79 years (mean = 63), all were high school graduates, and 52% had a college or postgraduate degree. Twenty-six percent answered 0 or only 1 of the numeracy questions correctly, 37% answered 2 correctly, and 37% answered all 3 correctly. Among women with the lowest level of numeracy, the correlation between utility for current health and self-reported health was in the wrong direction (i.e., worse health valued higher than better health): for standard gamble, Spearman r = -0.16, P =0.44; for time trade-off, Spearman r = -0.13, P = 0.54. Among the most numerate women, the authors observed a fair to moderate positive correlation with both standard gamble (Spearman r = 0.22, P = 0.19) and time trade-off (Spearman r = 0.50, P = 0.002). In contrast, using the visual analog scale, the authors observed a substantial correlation in the expected direction at all levels of numeracy (Spearman r =0.82, 0.50, and 0.60 for women answering 0-1, 2, and 3 numeracy questions, respectively; all P s ≤ 0.003). With regard to the imagined health states, the most feared disease had the lowest utility for 35% of the women with the lowest numeracy compared to 76% of the women with the highest numeracy (P = 0.03). Conclusions. The validity of standard utility assessments is related to the subject’s facility with numbers. Limited numeracy may be an important barrier to meaningfully assessing patients’ values using the standard gamble and time trade-off techniques.