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Purpose: Screening guidelines for breast cancer (BC) in transgender male (TM) patients are not well defined. This study describes referral patterns and compliance with referral for BC screening among TM patients receiving care at a tertiary care center. Methods: This was a retrospective cohort study of TM patients, 40–74 years of age, presenting for care between 2017 and 2020. The electronic medical record was queried for medical history and cancer screening data. Compliance with referral and screening was defined as occurring within 2 years of when screening would be expected. Results: Of the 266 patients identified, 45 met inclusion criteria. One (2.2%) had a history of BC, 0 (0%) had hereditary BC risk, and 11 (24.4%) had a family history of BC. Of the patients, 18 (40%) were referred for BC screening, of whom 13 (72.2%) were compliant with screening. Ten (55.6%) were referred by a primary care provider, 2 (11.1%) were referred by a transgender medicine specialist, and 6 (33.3%) were referred by both. Of the cohort, 27 (60%) had undergone masculinizing mastectomy. Six (22.2%) of these patients were referred for screening, of whom 0 (0%) had pre-screening clinical findings indicating need for screening. Of the 18 (40%) patients who had not undergone masculinizing mastectomy, 12 (66.7%) were referred for BC screening. Conclusions: There was heterogeneity in referral patterns for BC screening between TM patients who had undergone masculinizing mastectomy and those who had not. BC screening guidelines should be established for TM patients who have undergone masculinizing mastectomy. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is hypothesized to impact tumor progression by altering tumor metabolism. In this study, we assessed the impact of an unrestricted KD on epithelial ovarian cancer (EOC) tumor growth, gene expression, and metabolite concentration in a mouse model. ID8 EOC cells, which were syngeneic with C57Bl/6J mouse strain and transfected with luciferase (ID8-luc), were injectedand monitored for tumor development. Female mice were fed either a strict KD, a high fat/low carbohydrate (HF/LC) diet, or a low fat/high carbohydrate (LF/HC) diet (n = 10 mice per group) ad libitum. EOC tumor growth was monitored weekly, and tumor burden was determined based on luciferase fluorescence (photons/second). At the endpoint (42 days), tumors were collected and processed for RNA sequencing. Plasma and tumor metabolites were evaluated using LC-MS. The KD-fed mice exhibited a statistically significant increase in tumor progression in comparison to the HF/LC- and LF/HC-fed groups (9.1 vs. 2.0 vs. 3.1-fold, respectively, p < 0.001). The EOC tumors of the KD-fed mice exhibited significant enrichment of the peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid metabolism pathways based on the RNA sequencing analysis when compared to the LF/HC- and HF/LC-fed mice. Thus, unrestricted KD diet enhanced tumor progression in our mouse EOC model. KD was associated with the upregulation of fatty acid metabolism and regulation pathways, as well as enrichment of fatty acid and glutamine metabolites. [ABSTRACT FROM AUTHOR]

The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer‐related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat‐secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we now know that additional adipokines can impact tumorigenesis. A deeper understanding of the adipokine‐activated signaling in cancer may identify new treatment strategies irrespective of obesity. Moreover, adipokines may serve as disease biomarkers, harnessing the potential of obesity‐associated factors to serve as indicators of treatment response and disease prognosis. As studies investigating obesity and women's cancers continue to expand, it has become evident that breast, ovarian, and uterine cancers are distinctly impacted by adipokines. While complex, these distinct interactions may provide insight into cancer progression in these organs and new opportunities for targeted therapies. This review aims to organize and present the literature from the last 5 years investigating the mechanisms and implications of adipokine signaling in breast, endometrial, and ovarian cancers with a special focus on leptin and adiponectin. [ABSTRACT FROM AUTHOR]

Purpose: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG.Methods and Materials: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed.Results: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016).Conclusions: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex. [ABSTRACT FROM AUTHOR]

Purpose of Review: We review the emerging evidence regarding the relationship between the microbiota of the gastrointestinal and female reproductive tracts and gynecologic cancer. Recent Findings: The microbiome has essential roles in maintaining health. In recent years, the microbiota of the gastrointestinal and female reproductive tracts have been linked to many diseases, including gynecologic cancer. Alterations to the bacterial populations in a microbiota, or dysbiosis, have been shown to favor a pro-carcinogenic state through altered immune responses, dysregulated hormone metabolism, and modulation of the cell cycle. Pre-clinical and clinical studies have emerged, demonstrating that specific bacteria or microbial communities may be associated with increased risk for uterine, ovarian, and cervical cancers. Notably, numerous studies have linked a non-Lactobacillus-dominant vaginal microbiota, composed of anaerobic bacteria, with HPV infection, persistence, and development of invasive cervical cancer. Similarly, next-generation high-throughput sequencing techniques have enabled the characterization of unique microbiotas in patients with malignant and benign gynecologic conditions, shedding light on new associations between bacterial species and gynecologic cancers. Harnessing the power of the microbiome for early diagnosis, therapeutic intervention and modulation creates tremendous potential to optimize gynecologic cancer outcomes in the future. [ABSTRACT FROM AUTHOR]

Objectives: The ketogenic diet (KD) is hypothesized to protect against cancer progression due to metabolic reprogramming. Sustained dietary modifications alter the composition of the gut microbiome, which may influence tumor growth. Here, we present the impact of KD on the gut microbiome in relation to epithelial ovarian cancer (EOC) progression. Methods: C57Bl/6J ID8 (luciferase-tagged) tumor-bearing mice were fed a KD (10% protein, 0% carbohydrates, 90% fat), high fat diet (HFD) (10% protein, 15% carbohydrates, 75% fat), and control diet (CD) (10% protein, 77% carbohydrates, and 13% fat) (n =10 mice per group). Blood ketone and glucose levels were serially measured. EOC tumor growth was monitored with in Vivo Imaging System (IVIS) via intraperitoneal D-luciferin. Total tumor burden was measured in total flux (photons/second). Stool was collected at baseline, midpoint (four weeks after tumor cell injection), and endpoint (tumor mass of >150 mm3, ascites development, or weight loss >20%); 16S rDNA was isolated, and sequence reads were assigned to genus-level amplicon sequence variants (ASV) in DADA2 as well as analyzed for alpha and beta microbial diversity using Phyloseq. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression, and Wilcoxon test. A p-value of <0.05 was considered statistically significant. Results: KD-fed mice exhibited an increase in ketone blood levels (2.22 mmol/L) compared to both HFD- (0.7 mmol/L, p<0.0001) and CD-fed mice (0.61 mmol/L, p<0.0001) at the endpoint. There was no significant difference in overall glucose levels or body mass composition between the groups. By day 42, there was a 9.1-fold increase in tumor growth from baseline in the KD-fed group compared to HFD-and CD-fed groups (9.1 vs 2.0 vs 3.1-fold, respectively, p<0.001 and p<0.001). By study endpoint, KD-fed mice exhibited a statistically significant increase in gut microbial alpha diversity in comparison to HFD and CD (p<0.01 at the midpoint and p<0.05 at the endpoint). Brays-Curtis dissimilarity based on microbial beta diversity demonstrated that the relative abundance of gut microbial species between the three groups was similar at baseline. However, KD-fed mice had significantly altered gut microbial composition than HFD-and CD-fed mice at both midpoint and endpoint (p = 0.001); 16S data analysis demonstrated a relative decrease in Lactobacillus and Coriobacteriaceae species and a relative increase in Romboutsia and Akkermansia species in the KD-fed mice. Conclusions: In our EOC murine model, KD was associated with increased EOC growth and distinct gut microbial alterations in comparison to HFD and CD. KD-fed mice exhibited increased gut microbial diversity over time, a relative depletion of bacterial species Lactobacillus and Coriobacteriaceae , and a relative enrichment of bacterial species Romboutsia and Akkermansia. Further studies are needed to understand the mechanisms underlying the relationship between KD, the gut microbiome, and EOC progression. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: The ketogenic diet (KD) is hypothesized to impact tumor progression indirectly through altering the immune system as well as directly at the cellular level. Our studies were designed to assess changes in tumor resident immune cells and tumor gene expression in relation to epithelial ovarian cancer (EOC) progression in KD-fed mice. Methods: ID8 EOC cells, syngeneic with C57Bl/6J mouse strain, transfected with luciferase (ID8-Luc), were injected and monitored for tumor development via imaging with an in vivo Imaging System (IVIS) intraperitoneal D-luciferin. Tumor-bearing mice were fed a KD (10% protein, 0% carbohydrates, 90% fat), high fat diet (HFD) (10% protein, 15% carbohydrates, 75% fat), or control diet (CD) (10% protein, 77% carbohydrates, and 13% fat) (n =10 mice per group). EOC tumor growth was monitored weekly, and tumor burden was determined based on total flux recorded in photons/second measured. At the endpoint, tumors were collected and processed for flow cytometry and RNAseq analysis. Single-cell dissociated tumors (Papain System) were stained with an immune targeted antibody panel and analyzed on the BD Cytek Aurora. RNA was isolated (Qiagen), and sequencing was performed. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression, and Wilcoxon test; a p-value of <0.05 was considered statistically significant. Results: Throughout the study, KD-fed mice exhibited a statistically significant increase in tumor progression. We observed a 9.1-fold increase in tumor volume from baseline in the KD-fed group compared to HFD and CD-fed groups (9.1 vs 2.0 vs 3.1-fold, respectively, p<0.001). At the endpoint, tumor-associated macrophages (TAM) were significantly enriched and activated lymphoid cells (NK cells) were significantly diminished in the KD group (p<0.001). There was a trend toward increased M2:M1 polarization in KD-fed mice. However, there was no significant difference in Treg cells or activated CD8+ cells among diet groups. EOC tumors in KD-fed mice exhibited a significant decrease in differential gene expression on RNA seq compared to CD- and HFD-fed tumors, with no significant difference between CD- and HFD-fed groups at the gene expression level. Gene set enrichment analysis (GSEA) demonstrated that EOC tumors from KD-fed mice had enhanced angiogenesis, inflammatory response, and epithelial to mesenchymal transition (EMT) phenotype, as well as altered lipid metabolism. Specifically, an increase in lipid catalytic activity and catabolism and decrease in lipid synthesis were noted among KD-fed mice versus HFD-fed mice. Conclusions: KD induced tumor progression in our murine EOC model compared to HFD and CD. KD was associated with an increase in TAM and a decrease in activated NK cells consistent with a protumorigenic immune environment. KD-fed mice exhibited markedly increased alterations in angiogenesis, inflammation, and EMT pathways with enhanced lipid catabolic activity. Further testing of KD in human EOC cells is needed to clarify the in-vivo effect of KD on EOC growth. [Display omitted] [ABSTRACT FROM AUTHOR]