Validation of a clinical breast cancer risk assessment tool combining a polygenic score for all ancestries with traditional risk factors.

PURPOSE: We previously described a combined risk score (CRS) that integrates a multiple-ancestry polygenic risk score (MA-PRS) with the Tyrer-Cuzick (TC) model to assess breast cancer (BC) risk. Here, we present a longitudinal validation of CRS in a real-world cohort. METHODS: This study included 130,058 patients referred for hereditary cancer genetic testing and negative for germline pathogenic variants in BC-associated genes. Data were obtained by linking genetic test results to medical claims (median follow-up 12.1 months). CRS calibration was evaluated by the ratio of observed to expected BCs. RESULTS: Three hundred forty BCs were observed over 148,349 patient-years. CRS was well-calibrated and demonstrated superior calibration compared with TC in high-risk deciles. MA-PRS alone had greater discriminatory accuracy than TC, and CRS had approximately 2-fold greater discriminatory accuracy than MA-PRS or TC. Among those classified as high risk by TC, 32.6% were low risk by CRS, and of those classified as low risk by TC, 4.3% were high risk by CRS. In cases where CRS and TC classifications disagreed, CRS was more accurate in predicting incident BC. CONCLUSION: CRS was well-calibrated and significantly improved BC risk stratification. Short-term follow-up suggests that clinical implementation of CRS should improve outcomes for patients of all ancestries through personalized risk-based screening and prevention.

Emerging From the Haze™: Pilot Feasibility Study Comparing Two Virtual Formats of a Cognitive Rehabilitation Intervention.

OBJECTIVES: To gather feasibility and preliminary data comparing two virtual delivery methods for providing Emerging From the Haze™ (Haze) to cancer survivors compared to waitlist control (WLC). SAMPLE & SETTING: Eligible participants (N = 93) reported cancer-related cognitive impairment following chemotherapy for stage I-III solid tumors, Hodgkin lymphoma, or non-Hodgkin lymphoma. METHODS & VARIABLES: A three-arm randomized design was used to compare virtual live group presentation of Haze sessions, virtual prerecorded Haze group sessions, and WLC. Data were collected at baseline, week 10, and week 14. RESULTS: Feasibility was demonstrated. Significant cognitive function improvement at week 10 versus WLC was reported for the live group, and clinical improvement was reported for the prerecorded group. The prerecorded group reported significant improvement at week 14 versus WLC in physical activity, sleep, and health-related quality of life. IMPLICATIONS FOR NURSING: Additional pilot and feasibility evidence for cognitive rehabilitation interventions was demonstrated. Prerecorded Haze delivery shows potential for clinical effectiveness and scalability. Future multisite research is warranted.