From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Background Typically, women in South Africa (SA) are diagnosed with breast cancer when they self-present with symptoms to health facilities. The aim of this study was to determine the pathway that women follow to breast cancer care and factors associated with this journey. Methods A cross-sectional study was conducted at a tertiary hospital in the Western Cape Province, SA, between May 2015 and May 2016. Newly diagnosed breast cancer patients were interviewed to determine their socio-demographic profile; knowledge of risk factors, signs and symptoms; appraisal of breast changes; clinical profile and; key time events in the journey to care. The Model of Pathways to Treatment Framework underpinned the analysis. The total time (TT) between a woman noticing the first breast change and the date of scheduled treatment was divided into 3 intervals: the patient interval (PI); the diagnostic interval (DI) and the pre-treatment interval (PTI). For the PI, DI and PTI a bivariate comparison of median time intervals by various characteristics was conducted using Wilcoxon rank-sum and Kruskal-Wallis tests. Cox Proportional-Hazards models were used to identify factors independently associated with the PI, DI and PTI. Results The median age of the 201 participants was 54 years, and 22% presented with late stage disease. The median TT was 110 days, with median patient, diagnostic and pre-treatment intervals of 23, 28 and 37 days respectively. Factors associated with the PI were: older age (Hazard ratio (HR) 0.59, 95% CI 0.40–0.86), initial symptom denial (HR 0.43, 95% CI 0.19–0.97) and waiting for a lump to increase in size before seeking care (HR 0.51, 95% CI 0.33–0.77). Women with co-morbidities had a significantly longer DI (HR 0.67, 95% CI 0.47–0.96) as did women who mentioned denial of initial breast symptoms (HR 4.61, 95% CI 1.80–11.78). The PTI was associated with late stage disease at presentation (HR 1.78, 95% CI 1.15–2.76). Conclusion The Model of Pathways to Treatment provides a useful framework to explore patient’s journeys to care and identified opportunities for targeted interventions

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial

Additional file 2: of From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Predictors of the Patient Interval. Table with results of the Cox Regression analysis (DOCX 17 kb

Additional file 1: of From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Pathways to breast cancer care questionnaire. (PDF 344 kb

Additional file 4: of From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Predictors of the Pre-Treatment Interval. Table with results of the Cox Regression analysis (DOCX 14 kb

Additional file 3: of From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

Predictors of the Diagnostic Interval. Table with results of the Cox Regression analysis (DOCX 15 kb

Sleep and cognition in South African patients with non-functioning pituitary adenomas.

Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients' cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter

Between-group differences on BTACT Bi-factor outcome variables: Radiotherapy versus no radiotherapy.

Between-group differences on BTACT Bi-factor outcome variables: Radiotherapy versus no radiotherapy.</p

Regression analysis: Group status (NFPA patients versus healthy controls) as a predictor of sleep quality and cognitive performance (N = 37).

Regression analysis: Group status (NFPA patients versus healthy controls) as a predictor of sleep quality and cognitive performance (N = 37).</p

Sample sociodemographic characteristics (N = 37).

Strong lines of evidence in the neuroscience literature indicate that (a) healthy sleep facilitates cognitive processing, and (b) sleep disruption is associated with cognitive dysfunction. Despite the fact that patients with pituitary disease often display both disrupted sleep and cognitive dysfunction, few previous studies investigate whether these clinical characteristics in these patients might be related. Hence, we explored whether sleep disruption in patients with pituitary disease mediates their cognitive dysfunction. We recruited 18 patients with non-functioning pituitary adenomas (NFPA) and 19 sociodemographically matched healthy controls. They completed the Global Sleep Assessment Questionnaire (thus providing self-report data regarding sleep disruption) and were administered the Brief Test of Adult Cognition by Telephone, which assesses cognitive functioning in the domains of processing speed, working memory, episodic memory, inhibition, and reasoning. We found no significant differences in cognition between patients and controls. Furthermore, spectra of sleep disturbance did not differ significantly between patients and controls. Our data suggest that NFPA patients’ cognition and sleep quality is relatively intact, and that sleep disruption does not mediate cognitive dysfunction. Larger studies should characterize sleep and cognition in patients with NFPA (and other pituitary diseases) to confirm whether disruption of the former mediates impairment in the latter.</div