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.

Factors Influencing Patient Confidence in Screening Mammography.

BACKGROUND: We aimed to assess factors associated with patients' confidence in the ability of screening mammography to detect breast cancer. METHODS: Data were analyzed from a cross-sectional, prospective survey conducted in 2017 of women without a breast cancer history who were undergoing screening mammography at our institution. RESULTS: In total, 390 women completed the survey questions relevant to this study. Most respondents were 46 years or older (89.7%), White (87.6%), and college-educated (66.1%). Approximately 80% of respondents reported having confidence in the ability of screening mammography to detect breast cancer. Factors significantly associated with lower confidence in screening mammography were higher education (P = .01) and dense breast tissue (P < .001). Age (P = .12), race (P = .64), family history of breast cancer (P = .17), prior abnormal mammogram (P = .07), and mammogram frequency (P = .42) were nonsignificant. Women with a college education or higher were less likely to report confidence in routine mammography than women with less education (odds ratio [OR]= 0.43; 95% CI, 0.20-0.84; P = .02). Compared with women who reported their breast tissue as not dense, women who were aware they had increased breast density (OR = 0.16; 95% CI, 0.04-0.49; P = .004) or were unaware whether they had increased breast density (OR = 0.17; 95% CI, 0.04-0.51; P = .005) reported less confidence in screening mammography. DISCUSSION: Most respondents were confident in the ability of screening mammography to detect breast cancer. Confidence was inversely associated with education level and self-reported increased breast density. CONCLUSIONS: These findings highlight the importance of continued patient education about the effectiveness of screening mammography for patients with dense breast tissue.

Breast Cancer Polygenic-Risk Score Influence on Risk-Reducing Endocrine Therapy Use: Genetic Risk Estimate (GENRE) Trial 1-Year and 2-Year Follow-Up.

Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors. PREVENTION RELEVANCE: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.