Background Cardiovascular disease is the primary cause of death among patients with breast cancer. However, the association of cardiovascular-disease risk factors (CVD-RFs) with long-term survival and cardiac events is not well studied. Methods We examined SWOG (formerly the Southwest Oncology Group) breast cancer trials from 1999 to 2011. We identified baseline diabetes, hypertension, hypercholesterolemia, and coronary artery disease by linking trial records to Medicare claims. The primary outcome was overall survival. Patients with both baseline and follow-up claims were examined for cardiac events. Cox regression was used to assess the association between CVD-RFs and outcomes. Results We identified 1,460 participants older than 66 years of age from five trials; 842 were eligible for survival outcomes analysis. At baseline, median age was 70 years, and median follow-up was 6 years. Hypertension (73%) and hypercholesterolemia (57%) were the most prevalent conditions; 87% of patients had one or more CVD-RF. There was no association between any of the individual CVD-RFs and overall survival except for hypercholesterolemia, which was associated with improved overall survival (hazard ratio [HR], 0.73; 95% CI, 0.57 to 0.93; P = .01). With each additional CVD-RF, there was an increased risk of death (HR, 1.23; 95% CI, 1.08 to 1.40; P = .002), worse progression-free survival (HR, 1.12; 95% CI, 1.00 to 1.25; P = .05), and marginally worse cancer-free survival (HR, 1.15; 95% CI, 0.99 to 1.34; P = .07). The relationship between baseline CVD-RFs and cardiac events was analyzed in 736 patients. A strong linear association between the number of CVD-RFs and cardiac event was observed (HR per CVD-RF, 1.41; 95% CI, 1.17 to 1.69; P < .001). Conclusion Among participants in clinical trials, each additional baseline CVD-RF was associated with an increased risk of cardiac events and death. Efforts to improve control of modifiable CVD-RFs are needed, especially among those with multiple risk factors.

In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

Background It has long been assumed that in retinitis pigmentosa, disease presentation and progression are symmetrical. This study investigated whether hyperautofluorescent ring size, one known marker of disease progression, is symmetrical in typical RP patients. Materials and Methods A total of 88 patients with typical retinitis pigmentosa were enrolled in the study. Each presented with a hyperautofluorescent ring when imaged at baseline with fundus autofluorescence (AF). Vertical and horizontal diameters were analyzed according to mode of inheritance and age group. Seven of 88 patients had data missing in one eye and were excluded from further analysis. Results There was no significant relationship between hyperautofluorescent ring diameter and inheritance mode. There was a tendency toward smaller ring size with age and 3.7% of subjects displayed marked asymmetry in ring size between right and left eyes, although their electroretinogram results did not differ. Overall, when patients were considered as a group, there was a high correlation between right and left eyes’ horizontal and vertical diameters (r = 0.99, p<0.0001; r = 0.98, p<0.0001). Comparing individual patients’ eyes, and accounting for measurement error, a smaller majority of patients displayed symmetry of the hyperautofluorescent ring in both dimensions (85.7% in the vertical dimension, 87.3% in the horizontal dimension). Conclusion This study confirmed the highly symmetrical nature of the hyperautofluorescent ring in RP patients, except in a small subgroup. AF results, which provide less variability per image, and are consistently interpreted between different observers, may be a more sensitive and reliable method for testing symmetry than many functional tests.

Context Breast cancer is increasing in prevalence in parallel with rising rates of obesity worldwide. Obesity is recognized as a leading modifiable risk factor for the development of breast cancer; however, this association varies considerably by clinicopathologic features, and the underlying mechanisms are complex. Evidence Acquisition Pubmed literature search using combinations of “obesity,” “breast cancer risk,” “diet,” “exercise,“ “weight gain”, “weight loss”, “adipose tissue inflammation”, “crown-like structure”, “immune markers”, “metformin”, “gliflozins”, “SGLT-2i”, “GLP1-RA,” and related terms. Evidence Synthesis Elevated body mass index and weight gain are associated with increased risk of postmenopausal, hormone receptor-positive breast cancer. Emerging evidence suggests that adverse measures of body composition in individuals of any weight can also confer increased breast cancer risk. Mechanistically, various factors including altered adipokine balance, dysfunctional adipose tissue, dysregulated insulin signaling, and chronic inflammation contribute to tumorigenesis. Weight loss and more specifically, fat mass loss through lifestyle and pharmacologic interventions improve serum metabolic and inflammatory markers, sex hormone levels, and measures of breast density, suggesting a link to decreased breast cancer risk. Conclusion Incorporating markers of metabolic health and body composition measures with body mass index can capture breast cancer risk more comprehensively. Further studies of interventions targeting body fat levels are needed to curb the growing prevalence of obesity-related cancer.

Cancer cachexia is increasingly recognized as a poor prognostic marker for various tumor types. Weight loss in esophageal cancer is multifactorial, as patients with bulky tumors also have reduced ability to eat. We aimed to investigate the relationship between prediagnosis weight loss and mortality in esophageal cancer and to determine whether these associations vary with tumor stage. We conducted a prospective cohort study of esophageal cancer patients at two tertiary centers. We recorded baseline patient characteristics including medications, smoking, body mass index, and weight loss in the year prior to diagnosis, and collected data on treatment and outcomes. We used Cox regression modeling to determine the associations between percent weight loss and outcomes. The main outcome of interest was all-cause mortality; secondary endpoints were esophageal cancer-specific mortality and development of metastases. We enrolled 134 subjects, the majority of whom had adenocarcinoma (82.1%); median percent weight loss was 4.7% (IQR: 0%-10.9%). Increasing percent weight loss was not associated with all-cause mortality (ptrend = 0.36). However, there was evidence of significant interaction by tumor stage (p = 0.02). There was a strong and significant association between prediagnosis weight loss and mortality in patients with T stages 1 or 2 (adjusted HR 8.26 for highest versus lowest tertile, 95%CI 1.11-61.5, ptrend = 0.03) but not for T stages 3 or 4 (ptrend = 0.32). Body mass index one year prior to diagnosis was not associated with mortality. Prediagnosis weight loss was associated with increased all-cause mortality only in patients with early stage esophageal cancer. This suggests that tumor-related cachexia can occur early in esophageal cancer and represents a poor prognostic marker.

Purpose To report the phenotypes caused by a novel mutation in the PDE6B gene in a family with two affected siblings and one affected cousin with a 2-year follow-up. Design Three patients from a family with a history of retinitis pigmentosa underwent clinical evaluations. The affected patients’ DNA was analyzed using next-generation sequencing and segregation analyses were performed for the family. Setting Edward S. Harkness Eye Institute, New York Presbyterian Hospital. Participants Two siblings, one cousin, and five unaffected family members. Main outcome measures Macular appearance assessed by funduscopy, autofluorescence imaging, spectral-domain optical coherence tomography and visual function assessed by electroretinography. Results The proband, brother, and cousin had rod-cone degeneration with cystoid macular edema. Fundus autofluorescence showed hyperautofluorescent ring constriction over time. Spectral-domain optical coherence tomography revealed retinal pigment epithelium atrophy, loss of external limiting membrane, retinal layer thinning, and reduction in ellipsoid zone length over time. Next-generation whole exome sequencing revealed a homozygous c.1923_1969ins6del47 nonsense PDE6B mutation, which has not been previously described, that segregated with the disease in the family. Conclusions The homozygous PDE6B mutation causes retinitis pigmentosa. Acetazolamide treatment improved visual acuity but rod degeneration continued. Despite having the same mutation and living in the same environment, the proband’s brother progressed at a faster rate starting at a younger age, suggesting that gene modifiers may influence the expressivity of the phenotype. Next-generation sequencing, used to discover this mutation, is a practical new technology that can detect novel disease-causing alleles, where previous arrayed primer extension (APEX) technology could not.

Highlights Endometrial mesonephric-like adenocarcinoma (MLA) is a rare and aggressive subtype of epithelial endometrial cancer. KRAS mutations are characteristic in patients with endometrial MLA. We report two cases of KRAS -mutated endometrial MLA with excellent and durable responses to lenvatinib and pembrolizumab. Tumors with KRAS mutations may be particularly sensitive to lenvatinib, but this warrants further study.

No abstract