Mechanisms of stress-attributed breast cancer incidence and progression.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in women, with psychosocial stress commonly cited by patients as one of its causes. While there is conflicting epidemiological evidence investigating the association between psychosocial stress and breast cancer incidence and progression, there is reason to believe that interventions aimed at reducing stress pharmacologically or psychologically may improve breast cancer outcomes. The aim of this review is to discuss the molecular and biological mechanisms of stress-attributed breast cancer incidence and progression, including the induction of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as well as decreased immune function and stress hormone-induced resistance to chemotherapy. Moreover, these mechanisms have been cited as potential therapeutic targets of pharmacologic and psychological interventions that may improve the care, well-being and survival of breast cancer patients. Further research is recommended to investigate whether interventions in the primary care setting for women with risk factors for breast cancer development may lead to a decreased incidence of invasive breast tumors.

Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Mode of detection matters: Differences in screen-detected versus symptomatic breast cancers.

OBJECTIVE: Although extensive analyses evaluating screening mammography for breast cancer have been published, some utilized databases do not distinguish between modes of detection, which confounds the conclusions made about the impact of screening mammography. METHODS: A retrospective cohort study of women at our institution with pathologically-proven breast cancer from January 2015 to April 2018 was conducted. Subjects were categorized by their mode of diagnosis: screening or non-screening. Patient demographics, tumor characteristics, and treatments were compared between detection methods using Wilcoxon rank-sum test for continuous variables and chi-squared or Fisher's exact test. RESULTS: 1026 breast cancers were analyzed. 80.8% of screen-detected breast cancers were invasive. Compared to symptomatically detected cancers, screen-detected were smaller (median size 8 mm vs. 15 mm, p < 0.001), less invasive (80.8% vs. 94.3), had a lower pathologic grade (29% grade 3 vs. 45.7%, p < 0.001), a lower clinical stage, and less aggressive histology (51.9% low Ki67 vs. 30.5%, and 88.2% HER2 negative vs. 76.6%, p < 0.001). Screen-detected cancers were less likely to have extramammary disease (13.2% positive lymph nodes vs. 34.0% and 0.4% distant metastases vs. 6.9%, p < 0.001). Women with screen-detected cancers were more likely to undergo conservative treatment (74.8% underwent lumpectomy vs. 59.9%, and 80.0% received no chemotherapy vs. 51.3%, p < 0.001). CONCLUSION: In this study, while the vast majority of screen-detected cancers were invasive, they were more likely to be smaller, less aggressive, and a lower pathologic grade and clinical stage. Furthermore, women with screen-detected cancers were less likely to have extramammary disease and more likely to undergo conservative treatment.

Breast cancer in women under age 40: A decade of trend analysis at a single institution.

BACKGROUND: Women should be evaluated for breast cancer risk by age 30 to assess for screening need. Recent trends in breast cancer in this population may further inform recommendations. OBJECTIVE: The aim of this study was to analyze trends over time in the rate of breast cancer, tumor characteristics and treatment in women under age 40. METHODS: Retrospective cohort study of women under age 40 at our institution diagnosed with breast cancer from January 2007 to April 2018 was conducted. Patient demographics, tumor characteristics and treatment outcomes were collected. Descriptive statistics and the Mann-Kendell Trend test were calculated. Two-proportion z-tests were used to compare proportions of stage, pathology and treatment between 2007-2013 and 2014-2018. RESULTS: 197 women under age 40 were treated for a new diagnosis of breast cancer at our institution. A higher proportion of women were diagnosed with invasive carcinoma in 2013-2018 (91%) compared to 2007-2012 (78%), p = 0.008. A higher proportion of women were diagnosed with advanced stage disease (stage III-IV) in 2013-2018 (24%) compared to 2007-2012 (2%), p = 0.001. No statistically significant evidence for an increasing trend of overall rate of breast cancer over the last 11 years (p = 0.419) was observed. CONCLUSIONS: While no statistically significant increase in overall rate of breast cancer was noted, an increase in invasive and later staged breast cancers was observed. CLINICAL IMPACT: Rise in more aggressive cancers in a population that is largely not screened may have implications both on the individual young woman's morbidity as well as on a public health level.

Radiation and Immunotherapy in High-grade Gliomas: Where Do We Stand?

High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease. A combination of radiotherapy and immunotherapy may prove to be even more effective than either alone, and preclinical evidence suggests that hypofractionated radiotherapy can actually prime the immune system to make immunotherapy more effective. This review addresses the complications of the current radiotherapy regimen, various methods of immunotherapy, and preclinical and clinical data from combined radioimmunotherapy trials.