Emerging evidence suggests that BRCA1 pathway contributes to the behavior of sporadic triple negative breast cancer (TNBC), but little is known about the mechanisms underlying this association. Considering the central role that microRNAs (miRNAs) play in gene expression regulation, the aim of this study was to identify miRNAs specifically deregulated in TNBC and investigate their involvement in BRCA1 regulation. Using locked nucleic acid (LNA)-based microarrays, expression levels of 1919 miRNAs were measured in paraffin-embedded tissues from 122 breast tumors and 11 healthy breast tissue samples. Differential miRNA expression was explored among the main subtypes of breast cancer, and 105 miRNAs were identified as specific for triple negative tumors. In silico prediction revealed that miR-498 and miR-187-5p target BRCA1, and these results were confirmed by luciferase reporter assay. While miR-187-5p was found overexpressed in a luminal B cell line, miR-498 was highly expressed in a triple negative cell line, Hs578T, and its expression was negatively correlated with the levels of BRCA1. We functionally demonstrated that miR-498 inhibits BRCA1 in breast cancer cell lines, and showed that inhibition of miR-498 led to reduced proliferation in the triple negative cell line Hs578T. Our results indicate that miR-498 regulates BRCA1 expression in breast cancer and its overexpression could contribute to the pathogenesis of sporadic TNBC via BRCA1 downregulation.

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Purpose To explore the effect of type 2 diabetes mellitus (T2DM) on the risk of death among women with breast cancer (BC). Methods A survival analysis was conducted among a cohort of women diagnosed with BC between 2006 and 2012 in Spain (n = 4,493). Biopsy or surgery confirmed BC cases were identified through the state population-based cancer registry with information on patients’ characteristics and vital status. Physician-diagnosed T2DM was confirmed based on primary health care clinical history. Cox regression analyses were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for all-cause death. Analyses were adjusted for age, hospital size, several clinical characteristics (including BC stage and histology, among others) and treatment modalities. Results Among the 4,493 BC women, 388 (8.6%) had coexisting T2DM. Overall, 1,299 (28.9%) BC women died during the completion of the follow-up and 785 (17.5%) did so during the first five years after BC diagnosis, resulting in a five-year survival rate of 82.5%. The death rate was higher in women with T2DM (43.8% died during whole period and 26.0% during the first five years) when compared with women without T2DM (27.5% and 16.7%, respectively). Accordingly, all-cause mortality was higher in women with T2DM (aHR: 1.22; 95% CI 1.03–1.44), especially if T2DM was diagnosed before BC (aHR:1.24; 95% CI 1.03–1.50) and in women with BC diagnosed before 50 years (aHR: 2.38; 95% CI 1.04–5.48). Conclusions T2DM was associated with higher all-cause mortality among Spanish women with BC, particularly when the T2DM diagnosis was prior to the BC.

This study was designed to adapt the Breast Cancer and Lymphedema Symptoms Experience Index (BCLE-SEI) to the Spanish language (BCLE-SEI-Es) and to assess its psychometric properties in Spanish-speaking women diagnosed with breast cancer. 286 breast cancer survivors were recruited. Study measured demographic and medical data and the BCLE-SEI. Reliability was measured using Cronbach’s alpha and test-retest reliability (n = 29) after an interval of two weeks. A robust principal components analysis was conducted to explore the dimensions of each BCLE-SEI-Es subtest. Discriminant power of the BCLE-SEI was assessed through a non-parametric test evaluating score differences between non-lymphedema and lymphedema patients. A cut-off point was established via a ROC curve. Cronbach’s alpha: all scales had a value above 0.9. Test-retest reliability: Correlations between questionnaire administrations were above 0.7. The first and second subtests showed a good fit to a unidimensional and two-factor structure, respectively. Lymphedema patients score significantly higher in all BCLE-SEI scales (p < 0.001). A cut-off point was established to predict a possible lymphedema case. The BCLE-SEI-Es is a valid, reliable tool for assessing and identifying the presence of lymphedema among breast cancer survivors and assessing its impact on the physical, functional, psychological and emotional aspects.

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