Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer

Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study

Background: The etiology of pancreatic cancer remains elusive. Several studies have suggested a role for diabetes mellitus, but the magnitude of its contribution remains controversial. Objectives: Utilizing a large administrative database, this retrospective cohort study was designed to investigate the relationship between type 2 diabetes mellitus and pancreatic cancer. Patients and design: Using the Veterans Integrated Services Network 16 database, 322,614 subjects were enrolled in the study, including 110,919 with type 2 diabetes mellitus and 211,695 diabetes-free controls matched by gender, year of birth and healthcare facility. Results: A significantly higher incidence of pancreatic cancer was observed in patients with type 2 diabetes mellitus, with an adjusted hazard ratio (95% confidence interval) of 2.17 (1.70–2.77) for type 2 diabetes mellitus compared to controls (p < 10 −9 ) after controlling for the matching factors. Conclusion: The association between type 2 diabetes mellitus and pancreatic cancer was statistically significant and may, in part, explain the rising incidence of pancreatic cancer

Relevance of Pathological Complete Response after Neoadjuvant Therapy for Breast Cancer

Breast cancer is a heterogeneous disease, and the different biological subtypes have different prognostic impacts. Neoadjuvant trials have recently become popular as they offer several advantages compared to traditional adjuvant trials. Studies have shown that patients who achieve pathological complete response (pCR) after neoadjuvant treatment have a better long-term outcome. Consequently, increasing the rate of pCR became the end point of neoadjuvant trials with the expectation of translation into improved survival. However, the definition of pCR has lacked uniformity, and the prognostic impact of achievement of pCR on survival in different breast cancer subtypes is uncertain. In this review, we present the controversies associated with the use of pCR as an end point in neoadjuvant trials

Relevance of Pathological Complete Response after Neoadjuvant Therapy for Breast Cancer

Breast cancer is a heterogeneous disease, and the different biological subtypes have different prognostic impacts. Neoadjuvant trials have recently become popular as they offer several advantages compared to traditional adjuvant trials. Studies have shown that patients who achieve pathological complete response (pCR) after neoadjuvant treatment have a better long-term outcome. Consequently, increasing the rate of pCR became the end point of neoadjuvant trials with the expectation of translation into improved survival. However, the definition of pCR has lacked uniformity, and the prognostic impact of achievement of pCR on survival in different breast cancer subtypes is uncertain. In this review, we present the controversies associated with the use of pCR as an end point in neoadjuvant trials