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Background: Recently, the classification of HER2 status evolves from binary to ternary, and HER2-low expression may exhibit prognostic significance. We aimed to investigate whether HER2-low tumor is distinct from HER2-zero or HER2-positive tumors, and then to develop a modified staging system (mNeo-Bioscore) that incorporates HER2-low status into Neo-Bioscore. Patients and Methods: This cohort study was conducted using data from the prospective database on breast cancer patients between January 2014 and February 2019. Results: Among 259 patients enrolled in the study, the HER2-low tumor exhibited significantly lower histological grade, pathological staging and Ki-67 level than the other two groups. HER2-low patients and HER2-positive patients receiving concurrent HER2-directed therapy may have similar LRFS (p = 0.531) and OS (p = 0.853), while HER2-zero peers may have significantly worse LRFS (p = 0.006) and OS (p = 0.017). In particular, a similar trend was also found in the patients without pathological complete response after surgery. Incorporation of HER2-low status made improvement in fit: 5-year OS rate estimates ranged from 33.33% to 100% for mNeo-Bioscore vs 61.36% to 100% for Neo-Bioscore. Conclusions: This study demonstrated that HER2-low tumor may exhibit prognostic significance. The innovative mNeo-Bioscore, based on a new classification of HER2 status, may serve as a prognostic staging system superior to Neo-Bioscore. [ABSTRACT FROM AUTHOR]

We aimed to explore the value of contrast-enhanced ultrasound (CEUS) in early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NAC). LABC patients who underwent CEUS before and during NAC from March 2014 to October 2018 were included and assessed. Logistic regression analysis and the Cox proportional hazards model were used to identify independent variables associated with pCR and RFS. Among 122 women, 44 underwent pCR. Molecular subtype, peak intensity (PEAK) and change in diameter were independent predictors of pCR after one cycle of NAC (area under the receiver operating characteristic curve [AUC], 0.81; 95% CI: 0.73, 0.88); Molecular subtype, PEAK and change in time to peak (TTP) were independently associated with pCR after two cycles of NAC (AUC, 0.85; 95% CI: 0.77, 0.91). A higher clinical T (hazard ratio [HR] = 4.75; 95% CI: 1.75, 12.87; p = 0.002) and N stages (HR = 3.39; 95% CI: 1.25, 9.19; p = 0.02) and a longer TTP (HR = 1.06; 95% CI: 1.01, 1.11; p = 0.02) at pre-NAC CEUS were independently associated with poorer RFS. CEUS can be used as a technique to predict pCR and RFS early in LABC patients treated with NAC. [ABSTRACT FROM AUTHOR]

CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted a retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolic status on liver dysfunction events, gynecological events and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], and intermediate metabolizers taking toremifene [IM + TOR]). A total of 192 patients were included in the study, with a median follow‐up time of 26.2 months. In EM + TAM cohort, the risks of liver dysfunction events (P =.004) and gynecological events (P =.004) were significantly higher compared to EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P =.14) and gynecological events (P =.99) were not significantly different from IM + TOR cohort. A significant decrease of total cholesterol was observed in EM + TAM cohort around 1 year after taking tamoxifen (P <.001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (P‐interaction =.007) and gynecological events (P‐interaction =.026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene. [ABSTRACT FROM AUTHOR]

Background: EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few. Methods: Patients treated with weekly paclitaxel–cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression. Results: Among all patients included in this study (n = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan–Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged <50 years. Pathway analysis revealed the top pathways that indicated the potential mechanisms of EPIC1 in chemoresistance, including the daunorubicin and doxorubicin metabolic processes. Conclusions: Our study suggests that EPIC1 may be a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer, specifically in the HorR-positive premenopausal subgroup. It may also help identify candidate responders and determine treatment strategies. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore whether the expression of serum miR-222-3p might contribute to early prediction of therapeutic response, clinical outcomes, and adverse events for HER2-positive breast cancer patients receiving neoadjuvant therapy (NAT). Methods: A total of 65 HER2-positive breast cancer patients receiving NAT were analyzed. The concentration of serum miR-222-3p was detected by quantitative real-time PCR. Logistic regression analysis was used to identify the association of serum miR-222-3p with pathological complete response (pCR). The relationship of serum miR-222-3p with disease-free survival (DFS) and overall survival (OS) was examined via log-rank test and Cox proportional hazards analysis. The ordered logistic regression was applied to evaluate the association between serum miR-222-3p and adverse events. Results: The miR-222-3p low group was more likely to achieve pCR [odds ratio (OR) = 0.258, P = 0.043]. The interaction between miR-222-3p and presenting Ki67 level was also detected for pCR (OR = 49.230, P interaction = 0.025). The miR-222-3p low group was correlated with superior DFS (P = 0.029) and OS (P = 0.0037). The expression of serum miR-222-3p was the independent protective factor for trastuzumab-induced cardiotoxicity (P < 0.05) and anemia (P = 0.013). Conclusions: Serum miR-222-3p is the potential factor to predict pCR, survival benefit and trastuzumab-induced cardiotoxicity for HER2-positive breast cancer patients receiving NAT. [ABSTRACT FROM AUTHOR]

Imaging-guided breast biopsy is crucial for breast lesion evaluation. We aim to make the first comprehensive comparison of two different ultrasound-guided breast biopsy devices: 14-G conventional core needle biopsy (CCNB) and the newly applied cable-free, low-vacuum-assisted 10-G breast biopsy system, Elite. We retrospectively collected patients with suspected breast cancer who underwent ultrasound-guided 14-G CCNB or 10-G Elite from October 2013 through March 2018 and compared the biopsy result with the result after operation. We analyzed the test performance of the two methods and their accuracy in immunohistochemistry assays mainly including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki67. We also analyzed the accuracy of 10-G Elite with frozen sections. Six hundred seventy-four patients who underwent 14-G CCNB and 592 patients who underwent 10-G Elite were finally included in the research. Negative predictive value with Elite was higher than with CCNB (Elite 86.5%, CCNB 41.7%, P < 0.001). Sensitivity (Elite 97.7%, CCNB 96.2%, P = 0.1), specificity (Elite 98.7%, CCNB 90.0%, P = 0.1), positive predictive value (Elite 99.8%, CCNB 99.7%, P = 0.7), and false negative rate (Elite 2.3%, CCNB 3.8%, P = 0.1) showed no difference between two devices. In terms of immunohistochemistry assay, Ki67 agreement of Elite was higher than that of CCNB (Elite 79.5%, CCNB 73.4%, P = 0.045). Estrogen receptor agreement (Elite 90.6%, CCNB 87.7%, P = 0.2), progesterone receptor agreement (Elite 83.9%, CCNB 80.9%, P = 0.3), and human epidermal growth factor receptor two agreement (Elite 94.2%, CCNB 93.5%, P = 0.7) showed no difference between Elite and CCNB. The rate of an inconclusive biopsy result was lower with Elite than with CCNB (Elite 1.5%, CCNB 3.3%, P = 0.045). 10-G Elite has higher negative predictive value, higher Ki67 agreement, and lower inconclusive results than 14-G CCNB. Elite can be a reliable substitute for 14-G CCNB. [ABSTRACT FROM AUTHOR]

Background: The aims of this study were to determine whether the quantitative HER2 gene amplification level is related to the key clinicopathological features that represent the aggressiveness of breast cancer (BC) and to determine whether the quantitative HER2 gene amplification level could predict the treatment response in the subset of HER2-positive patients who received neoadjuvant targeted therapy. Materials and methods: Patients treated with weekly cisplatin- and paclitaxel-based neoadjuvant chemotherapy, who had undergone both immunohistochemistry and the fluorescence in situ hybridization test for HER2, were included in the study (n=103). For HER2-positive patients, defined as immunohistochemistry score 3+ or fluorescence in situ hybridization ratio ≥2.0, trastuzumab was recommended with neoadjuvant chemotherapy (n=45). Pathological complete response was defined as complete pathological remission of tumor cells both in breast and axillary lymph nodes postoperation. Results: In all patients enrolled in the study, a higher HER2 amplification level was significantly correlated with larger tumor size and the absence of ER and PR expression. In HER2-positive patients treated with neoadjuvant trastuzumab concurrent with chemotherapy, both univariate and multivariate logistic regression showed that a higher HER2/CEP17 ratio and HER2 gene copy number were associated with a higher pathological complete response rate. When calculated by receiver operating characteristics analysis, an optimal cutoff of 4.5 for the HER2/CEP17 ratio was expected to distinguish the most sensitive candidate for treatment with a combination of trastuzumab and neoadjuvant chemotherapy. Conclusion: A higher HER2 amplification level was correlated with larger tumor size and reduced ER and PR expression, which may indicate more aggressive tumor behavior. For HER2-positive patients, the HER2/CEP17 ratio and HER2 gene copy number may be good predictive factors for concurrent neoadjuvant trastuzumab and chemotherapy. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the association of alpha 2a and beta2 adrenoceptor (AR) expression with tumor-relevant biological markers and clinical outcome. Topics discussed include the evaluation of the associations through the chi-square or Fisher's exact tests, the use of immunohistochemistry to localize antigens for alpha 2a AR in breast cancer, and disease-free survival in breast cancer patients.

The original article [1] contained an error in Fig. 7c whereby the same flow image was accidentally misused for the second and fourth group. [ABSTRACT FROM AUTHOR]