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.

Current State of Evidence-Based Long-Term Monitoring Protocols for Breast Plastic Surgery Patients.

BACKGROUND: Recommendations for breast surveillance following breast plastic surgery are frequently changing. Establishing guidelines for long-term monitoring protocols may help identify treatable conditions and prevent untoward sequelae. We sought to evaluate the current state of evidence-based long-term monitoring protocols for patients following breast augmentation, reduction, and breast reconstruction. METHODS: Official guidelines from various American societies and international societies were analyzed for alignment in evidence-based recommendations regarding breast surveillance. RESULTS: The most recent US FDA update recommends magnetic resonance imaging or ultrasound starting 5-6 years after surgery and every 2-3 years thereafter. Discrepancies exist among professional societies: the American Society of Plastic Surgeons (ASPS) aligns with the FDA, while the American Society of Breast Surgeons and American College of Radiology (ACR) find no role for imaging for asymptomatic cases. Ultrasound is first-line for any implant concerns, with MRI if necessary. European societies oppose routine breast implant imaging. Breast reduction patients lack unique screening protocols; monitoring aligns with age and cancer risk factors. Following mastectomy and breast reconstruction, most organizations advocate for annual clinical examinations, with more frequent examinations initially. Evidence suggests that physical examination is sufficient to detect local cancer recurrence, with imaging only indicated if there is concern for recurrence. No surveillance imaging is recommended by the American Society of Clinical Oncology, National Comprehensive Cancer Network, or ASPS; however, ACR recommends mammography for autologous reconstruction only. CONCLUSION: Multispecialty and regulatory body alignment may promote provider and patient adherence. Ongoing studies of long-term outcomes are needed to strengthen the level of evidence for monitoring guidelines.

Racial disparities in breast cancer risk factors and risk management.

Racial disparities in breast cancer outcomes are well described across the spectrum of screening, diagnosis, treatment, and survivorship. Breast cancer mortality is markedly elevated for Non-Hispanic Black women compared with other racial and ethnic groups, with multifactorial causes. Here, we aim to reduce this burden by identifying disparities in breast cancer risk factors, risk assessment, and risk management before breast cancer is diagnosed. We describe a reproductive profile and modifiable risk factors specific to the development of triple-negative breast cancer. We also propose that screening strategies should be both risk- and race-based, given the prevalence of early-onset triple-negative breast cancer in young Black women. We emphasize the importance of early risk assessment and identification of patients at hereditary and familial risk and discuss indications for a high-risk referral. We discuss the subtleties following genetic testing and highlight "uncertain" genetic testing results and risk estimation challenges in women who test negative. We trace aspects of the obesity epidemic in the Black community to infant feeding patterns and emphasize healthy eating and activity. Finally, we discuss building an environment of trust to foster adherence to recommendations, follow-up care, and participation in clinical trials. Addressing relevant social determinants of health; educating patients and clinicians on factors impacting disparities in outcomes; and encouraging participation in targeted, culturally sensitive research are essential to best serve all communities.