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PURPOSEWomen with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake.METHODSBetween July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months.RESULTSAmong 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO.CONCLUSIONThe rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS. more...

Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of cardiomyopathy in patients with solid malignancies. CHIP has also been shown to increase T cell activation in heart failure patients. It is unclear whether CHIP can affect the risk of immune checkpoint inhibitor (ICI) myocarditis in patients with cancer treated with immunotherapy. Methods We enrolled patients with solid tumors in a prospective study, determined CHIP status at time of enrollment through blood whole exome sequencing, and assessed incidence of ICI myocarditis from time of enrollment through December 1st, 2023. We performed a competing risk cox regression to evaluate the role of CHIP in ICI myocarditis, accounting for patient demographics, cardiac comorbidities, cardiotoxic cancer therapy, and dual ICI use in our covariates. We also generated cumulative incidence curves using subdistribution hazards to evaluate development of ICI myocarditis stratified by CHIP vs no CHIP. Chart review was performed to evaluate patient co-morbidities, lab values, imaging findings and outcomes. Results Among the 88 patients receiving ICI therapy, average age was 67 ± 14 years, of which 50% harbored CHIP variants. Among all comorbidities, including diabetes, heart failure and obstructive coronary artery disease, only coronary artery calcifications were significantly increased in patients with CHIP. There were no statistically significant differences in cancer therapy or cardiovascular drugs between patients with and without CHIP. Among examined outcomes, patients with CHIP had a statistically higher rate of ICI myocarditis (overall: 57%, CHIP: 73% (32/44), no CHIP: 41% (18/44), p = 0.003) and death (CHIP: 60%, no CHIP 31%, p = 0.011). In a multivariate competing risk analysis, CHIP status doubled the risk of developing ICI myocarditis, similar to the risk of dual ICI use (CHIP status HR 2.74, 95% CI: 1.44–5.22, p = 0.002 vs dual ICI use HR 2.39, 95% CI: 1.11–5.14, p = 0.026). Conclusions This study is the first to show that CHIP independently increases risk of ICI myocarditis, with implications for risk stratification of patients prior to ICI initiation and frequency of cardiac monitoring. more...