Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptor‐1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)‐positive subtype breast cancer, and is considered one possible mechanism of endocrine resistance through cross‐talk between ER and growth factor receptor signaling. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, transcript and protein expression, and examined the relationships between FGFR1 status and clinicopathological parameters, including prognosis in 307 ER‐positive/HER2‐negative primary breast cancer patients treated with standard care at our institute. Most notably, a high level of FGFR1 protein expression was observed in 85 patients (27.7%), and was positively associated with invasive tumor size (P = 0.039). Furthermore, univariate analysis revealed that high FGFR1 protein expression was significantly correlated with poor relapse‐free survival rate (P = 0.0019, HR: 2.63, 95% confidence interval: 1.17–5.98), and showed a tendency towards an increase in recurrent events if the observation period extended beyond the 5 years of the standard endocrine treatment term. FGFR1 gain/amplification was found in 43 (14.0%) patients, which was only associated with higher nuclear grade (P = 0.010). No correlation was found between FGFR1 mRNA expression levels and any clinicopathological factors. Overall, the level of FGFR1 protein expression may be a biomarker of ER‐positive/HER2‐negative primary breast cancer with possible resistance to standard treatment, and may be a useful tool to identify more specific patients who would benefit from FGFR‐1 targeted therapy.

Expression of specific genes may allow selection of the most responsive patients for maximum tumor shrinkage with NAET.

Triple-negative breast cancer (TNBC) is characterized by aggressive clinicopathological features and is associated with a poor prognosis. Identifying patients that are non-responsive to chemotherapy remains a critical goal for effective personalized therapies. In the present study, the predictive value of exosomal microRNAs (miRNAs) was investigated in patients with TNBC. Exosomes were isolated from patients with TNBC undergoing neoadjuvant chemotherapy. Microarray-based miRNA profiles were compared between patients with pathological complete response (pCR; n=12) and non-pCR (n=12). Furthermore, the miRNA profiles of non-pCR patients with breast cancer recurrence were compared with those with no recurrence. A total of 16 differentially expressed exosomal miRNAs were identified between the patients with pCR and non-pCR by microarray analysis. Of these, a combined signature of four miRNAs (miR-4448, miR-2392, miR-2467-3p and miR-4800-3p) could be used to discriminate between pCR and non-pCR patients with TNBC with an area under the curve value of 0.7652. Furthermore, this study found 43 differentially expressed miRNAs between the patients with non-pCR and recurrence and non-pCR patients without recurrence. In network analysis, 'pathway in cancer', 'focal adhesion' and 'cell cycle' were identified as the crucial pathways in patients with non-pCR who also developed recurrence. Several exosomal miRNAs may be useful biomarkers to predict treatment efficacy for TNBC. The present study identified patients who were resistant to standard chemotherapy and therefore more likely to develop breast cancer recurrence.

Cardiotoxicity in the late phase after anthracycline drugs administration remains to be defined. Of the 44 patients who received anthracycline treatment, 7 were found to have cancer therapeutics–related cardiac dysfunction (CTRCD). The global longitudinal strain determined by echocardiography and myocardial extracellular volume fraction (ECV) determined by cardiac computed tomography (CCT) of the CTRCD(+) group were significantly higher than those of the control group and CTRCD(-) group, whereas there were no significant differences between the control and CTRCD(-) groups. Our findings indicated that CCT may be a tool comparable to echocardiography, indicating the effective evaluation of CTRCD by CCT.

BackgroundApolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a gene editing enzyme with cytidine deaminase activity and high expression of its mRNA in breast tumors have been shown to be associated with progressive cases and poor prognosis. In this study, we aimed to examine the relationship between the expression of APOBEC3B and the effect of neoadjuvant chemotherapy (NAC) using pretreatment biopsy tissue, and examined whether the expression of APOBEC3B influenced chemotherapy efficacy.MethodsWe retrospectively selected a total of 274 patients with primary breast cancer who received NAC in more than 4 courses and underwent surgery at our institute. We assessed the expression of APOBEC3B mRNA using pretreatment biopsy specimens of NAC by quantitative real-time PCR (qRT-PCR) and examined the relationship between APOBEC3B mRNA expression and sensitivity to chemotherapy using pathological complete response (pCR) as an indicator. Further, we assessed the prognostic value of APOBEC3B in the patients receiving NAC.ResultsAPOBEC3B mRNA expression levels were successfully assessed in 173 (63.1%) of the 274 specimens. The total pCR rate was 36.4% (n = 63). An association between APOBEC3B expression levels and pCR was observed (Wilcoxon test, P ≤ 0.0001). The patients were divided into two groups, low (n = 66) and high (n = 107), according to the APOBEC3B expression levels, using the cut-off value calculated by the receiver operating characteristics (ROC) curve for pCR. The rate of pCR was significantly higher among the patients in the high group than among those in the low group (47.7% vs 18.2%, P ≤ 0.0001). High APOBEC3B expression was significantly associated with high nuclear grade (P = 0.0078), high Ki-67 labeling index (P = 0.0087), estrogen receptor (ER) negativity (P ≤ 0.0001) and human epidermal growth factor receptor 2 (HER2) negativity (P = 0.032). Tumor size (P = 0.011), ER (P ≤ 0.0001), HER2 (P = 0.0013) and APOBEC3B expression (P = 0.037) were independent predictive factors for pCR in multivariate analysis. However, there was no association between APOBEC3B expression and prognosis.ConclusionsOur study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in breast cancer patients. In contrast to previous studies, APOBEC3B mRNA expression was not associated with breast cancer prognosis in patients receiving NAC.