Cancers

Philadelphia-Negative Myeloproliferative neoplasms (MPNs) are chronic clonal hematopoietic malignancies characterized by dysregulated myeloid proliferation, chronic inflammation, and an increased risk of thrombotic and hemorrhagic complications. In addition to disease-related morbidity, MPNs are associated with a substantial symptom burden that significantly impacts quality of life. Menopause is accompanied by hormonal changes that can produce symptoms overlapping with those of MPNs, complicating clinical assessment and management in affected women. This challenge is further compounded by the lack of disease-specific guidance on menopause management in women with MPNs and ongoing concerns regarding the thrombotic risk associated with hormone replacement therapy (HRT). This narrative review summarizes the current evidence on menopause in women with Philadelphia chromosome–negative MPNs, with particular focus on the safety and role of HRT, non-hormonal therapeutic alternatives, and supportive care strategies. We also propose a pragmatic clinical algorithm to support individualized menopause management in this high-risk population.

Background: Cancer screening disparities remain understudied, particularly among underrepresented groups at the county level. This study compared the use of preventive breast and colorectal cancer screening services between sexual and gender minority (SGM) adults and cisgender heterosexual adults in Missouri. Methods: The 2022 Missouri County-Level Study, a probabilistic survey of health-related behaviors in each county, was used to estimate breast and colorectal cancer (BC and CRC) screening prevalence. Screening prevalence was calculated using weighted samples, and regression models were used to adjust for demographic composition and age eligibility for both cancer sites. Results: Compared to cisgender heterosexual adults (n = 48,257), SGM adults (n = 2801) were significantly younger and more likely to reside in urban areas and be employed. Statewide, county-representative prevalence of breast cancer screening in the last 2 years was 75.6%, and colorectal cancer screening (i.e., colonoscopy in the last 10 years or sigmoidoscopy in the last 5 years) was 63.1%. In age-adjusted models for BC screening for participants (ages 40–74), age had a curvilinear association, increasing at younger ages but declining in later years. For CR screening (ages 45–75), age showed a strong, stable, positive effect. SGM adults had similar odds of breast cancer screening; however, for CRC, SGM adults had higher odds of ever being screened but similar odds to cisgender heterosexual adults of up-to-date screening. Differences largely reflect eligibility windows and initiation versus maintenance dynamics. Conclusions: In this large sample of Missouri county residents, breast cancer and colorectal cancer screening rates were comparable between SGM adults and cisgender heterosexual adults for up-to-date screening probability. Improving statewide cancer prevention will require addressing the broader structural and regional barriers that suppress screening uptake across Missouri communities. Impact: These findings demonstrate the importance of using age-appropriate, guideline-aligned analyses to accurately assess cancer screening equity and avoid overstating disparities among SGM populations. By identifying where differences do not exist, this work helps focus resources on the structural and regional barriers that continue to limit cancer prevention for all Missourians.

Background/Objectives: The Iroquois (IRX) family of homeobox genes regulates critical developmental processes, and emerging evidence suggests that their dysregulation contributes to cancer progression, particularly in relation to cancer stemness. Although their expression appears to be influenced by hormonal regulation, their potential roles in hormone-sensitive cancers remain incompletely understood. Methods: In this study, we performed a comprehensive, exploratory analysis of all six Iroquois genes (IRX1–IRX6) across prostate, breast, ovarian, and endometrial cancers. Using large-scale publicly available transcriptomic datasets, we systematically examined IRX gene expression patterns and their associations with tumour progression, prognosis, hormone regulation, drug response, and cancer stemness. Results:IRX3 and IRX5 were consistently elevated in estrogen-dependent tumours and IRX2 and IRX4 were notably upregulated in prostate cancer. Despite evidence of estrogen receptor 1 (ESR1) and androgen receptor (AR) binding near several IRX promoters, estrogen treatment assays showed that ESR1 binding at promoters alone was insufficient to induce IRX transcription. Clinically, IRX2 expression was associated with favourable outcomes in breast, endometrial, and ovarian cancers and showed correlations with stemness-related signatures in prostate cancer. Similarly, IRX4 expression was associated with stemness features in prostate and endometrial cancers. In addition, IRX6 expression showed associations with reduced sensitivity to abiraterone, suggesting a potential link with therapeutic resistance in these tumours. Conclusions: Collectively, these findings highlight the context-dependent expression patterns and clinical associations of IRX genes across hormone-driven cancers. While largely correlative, this study provides a framework for future functional investigations and suggests that selected IRXs may have potential utility as biomarkers for disease stratification and treatment response in hormone-sensitive cancers.