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The purpose of this study was to identify microRNAs (miRNAs) closely associated with the prognosis of triple-negative breast cancer (TNBC) and their possible targets. This study recruited 125 early-stage TNBC patients, including 40 cases in the experimental group (20 cases with poor prognoses vs. 20 cases with good prognoses) and 85 cases in the validation group (27 cases with poor prognoses vs. 58 cases with good prognoses). In the experimental group, miRNA microarray showed 34 differentially expressed miRNAs in patients with different prognoses. We selected 5 miRNAs for validation. The differential expression of miR-221-3p was further verified in the experimental and validation groups using real-time polymerase chain reaction (PCR). High miR-221-3p expression was associated with better 5-year disease-free survival (DFS) (HR = 0.480; 95% CI, 0.263–0.879; p = 0.017) of TNBC patients. High expression of its target gene PARP1 predicted poorer 5-year DFS (HR = 2.236, 95% CI, 1.209-4.136, p = 0.010). MiR-221-3p down-regulated PARP1 by targeting its 3'-untranslated region.In conclusion, low miR-221-3p expression may contribute to the poor outcome of TNBC patients through regulating PARP1. MiR-221-3p likely plays a role as a PARP1 inhibitor by directly regulating PARP1 expression, thereby affecting the prognoses of TNBC patients.

PurposeIt is widely accepted that aldehyde dehydrogenase (ALDH) activity is a signature of breast cancer stem cells, and high activity has been reported to be associated with poor clinical outcome. The aim of this study was to assess the expression of members of the ALDH family of isozymes in breast cancer tissues and to evaluate the implications of the results.MethodsWe analyzed paraffin-embedded tumor tissue from 160 patients with breast cancer. Immunohistochemistry (IHC) staining was performed on the slides using antibodies against different ALDH family members. We collated the IHC results with patient clinical characteristics and determined their prognostic value. In addition, we analyzed normal, hyperplastic, and carcinomatous tissues in situ to check their ALDH distributions.ResultsAll the tested ALDH members were detected in the various tissue types, but at different levels. Only ALDH 1A3 was found to be significantly associated with distant metastasis (p=0.001), disease-free survival (p<0.001), and overall survival (p<0.001).ConclusionThe level of ALDH 1A3 in breast cancer tissue is a predictive marker of a poor clinical outcome.

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BackgroundNeoadjuvant chemotherapy (NAC) is widely used in advanced breast cancer patients. However, there is little known about conversion frequency of estrogen receptor (ER) and/or progesterone receptor (PR) status for hormone receptor positive-breast cancer patients after NAC and their correlation with prognosis.MethodsIn this study, 231 breast cancer patients with residual disease after NAC were enrolled and divided into receptor stable group (having no conversion in both ER and PR status pre- and post-NAC) and any receptor conversion group (having any conversion in either ER or PR status). Univariate and multivariate survival analyses were used to compare survival differences between the two groups.ResultsFifty-five patients (23.8%) had ER and/or PR conversion after NAC. Younger patients (≤ 50 years) were more likely to have receptor conversion (P = 0.014). For 213 patients (92.2%) who received adjuvant endocrinotherapy after surgery, the 5-year disease free survival (DFS) estimates for patients in the any receptor conversion group (55.2%) was worse than patients in the receptor stable group (73.7%, Log-rank test, P = 0.015). While the 5-year overall survival estimates for patients with or without receptor conversion were not statistically different (86.0 vs. 82.4%, Log-rank test, P = 0.587). In multivariate Cox proportional hazard analyses, patients with any receptor conversion had worse DFS (hazard ratio, 1.995; 95% confidence interval, 1.130–3.521, P = 0.031).ConclusionsIt is necessary to recommend patients to test biomarkers in residual disease and pay more attention to patients who have any receptor conversion. These patients may need more individual therapy after surgery.

Human epidermal growth factor receptor 1 or 2 (HER1/2), and fibroblast growth factor receptor 1 (FGFR1) signaling serve critical roles in the progression of breast cancer; however, cross-talk between HER1/2 and FGFR1 signaling has not been extensively studied. In the present study, the copy number variation status of FGFR1 and HER1/2, and the clinical implications and prognostic relevance of this, were evaluated in invasive ductal breast cancer (IDC) tissue samples. Quantitative polymerase chain reaction and fluorescence in situ hybridization were used to assess gene copy number variation in IDC samples, and the clinical characteristics and survival curves of patients with IDC were analyzed. The amplification of FGFR1 was identified in 16.0% of the samples (12 of 75), of HER1 in 26.7% (20 of 75), of HER2 in 37.3% (28 of 75), and of FGFR1 and HER1/2 simultaneously in 8.0% (6 of 75). FGFR1 and HER1/2 co-amplification were significantly correlated with distant metastasis (P=0.035), recurrence (P=0.026) and decreased disease-free survival time (P=0.042). This was the case for patients undergoing endocrine therapy (P=0.002) and chemotherapy (P=0.044). Taken together, the results indicate that patients with FGFR1 and HER1/2 co-amplification may exhibit a less favorable prognosis compared with patients with either FGFR1, HER1/2 amplification or without amplification.