Long non-coding RNA LINC01559 serves as a competing endogenous RNA accelerating triple-negative breast cancer progression.

BACKGROUND: Long non-coding RNA (lncRNA) is an endogenous RNA over 200 nt in length involved in gene regulation. LINC01559 is a novel lncRNA that has been identified as a fundamental player in human cancer. However, its role in triple-negative breast cancer (TNBC) remains unknown. Here, we explored the expression, function and clinical implication of LINC01559 in TNBC. METHODS: RNA expression was detected by qRT-PCR analysis. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays were used to test cell viability, DNA synthesis rate, migration and invasion, respectively. The competing endogenous RNA (ceRNA) axis involved in LINC01559 was determined by RNA pull-down and luciferase reporter assays. The xenograft model was used to verify the function of LINC01559 in vivo. RESULTS: LINC01559 was significantly increased in TNBC tissues as compared to matched normal tissues, which was due to high levels of H3K4Me3 and H3K27Ac in the promoter region. Knockdown of LINC01559 inhibited TNBC cell proliferation, migration and invasion in vitro, and also retarded tumor growth and reduced lung metastasis in vivo. Mechanistically, LINC01559 served as a ceRNA that sponged miR-370-3p, miR-485-5p and miR-940, resulting in increasing the expression of a cohort of oncogenes, thus accelerating TNBC progression. CONCLUSIONS: Our data provide a comprehensive analysis of LINC01559 in TNBC, we found that LINC01559 functioned as a carcinogenic ceRNA via sponging miRNAs. Targeting of LINC01559 may be a potential treatment for TNBC patients.

Exosomal long noncoding RNA AGAP2-AS1 regulates trastuzumab resistance via inducing autophagy in breast cancer.

Trastuzumab has been widely used for treatment of HER-2-positive breast cancer patients, however, the clinical response has been restricted due to emergence of resistance. Recent studies indicate that long noncoding RNA AGAP2-AS1 (lncRNA AGAP2-AS1) plays an important role in cancer resistance. However, the precise regulatory function and therapeutic potential of AGAP2-AS1 in trastuzumab resistance is still not defined. In this study, we sought to reveal the essential role of AGAP2-AS1 in trastuzumab resistance. Our results suggest that AGAP2-AS1 disseminates trastuzumab resistance via packaging into exosomes. Exosomal AGAP2-AS1 induces trastuzumab resistance via modulating ATG10 expression and autophagy activity. Mechanically, AGAP2-AS1 is associated with ELAVL1 protein, and the AGAP2-AS1-ELAVL1 complex could directly bind to the promoter region of ATG10, inducing H3K27ac and H3K4me3 enrichment, which finally activates ATG10 transcription. AGAP2-AS1-targeting antisense oligonucleotides (ASO) substantially increased trastuzumab-induced cytotoxicity. Clinically, increased expression of serum exosomal AGAP2-AS1 was associate with poor response to trastuzumab treatment. In conclusion, exosomal AGAP2-AS1 increased trastuzumab resistance via promoting ATG10 expression and inducing autophagy. Therefore, AGAP2-AS1 may serve as predictive biomarker and therapeutic target for HER-2+ breast cancer patients.

lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy.

The regulatory mechanism of long non-coding RNAs (lncRNAs) in trastuzumab resistance is not well established to date. In this research, we identified differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. HiSeq sequencing and quantitative real-time PCR were performed to identify the dysregulated lncRNAs. Mass spectrometry, RNA fluorescence in situ hybridization (RNA-FISH), and immunoprecipitation assays were performed to identify the direct interactions between ZNF649-AS1 and other associated targets, such as polypyrimidine tract binding protein 1 (PTBP1) and autophagy related 5 (ATG5). Our results showed that ZNF649-AS1 was more highly expressed in trastuzumab-resistant cells compared to sensitive cells. Increased expression of ZNF649-AS1 was associated with a poorer response and shorter survival time of breast cancer patients. ZNF649-AS1 was upregulated by H3K27ac modification at the presence of trastuzumab treatment, and knockdown of ZNF649-AS1 reversed trastuzumab resistance via modulating ATG5 expression and autophagy. Mechanically, ZNF649-AS1 was associated with PTBP1 protein, which further promoted the transcription activity of the ATG5 gene. In conclusion, we demonstrated that H3K27ac modification-induced upregulation of ZNF649-AS1 could cause autophagy and trastuzumab resistance through associating with PTBP1 and promoting ATG5 transcription.

Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation.

BACKGROUND: Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer. METHODS: LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance. RESULTS: AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level. CONCLUSION: Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.

Exosome-mediated transfer of long noncoding RNA H19 induces doxorubicin resistance in breast cancer.

Development of the acquired resistance is one major obstacle during chemotherapy for cancer patients. Exosomes mediate intercellular communication and cause environmental changes in tumor progression by transmitting active molecules. In this study, the role of long noncoding RNA H19 within exosomes is elucidated in terms of regulating doxorubicin (DOX) resistance of breast cancer. As a result, increased H19 expression was observed in DOX-resistant breast cancer cells in comparison with the corresponding parental cells. Suppression of H19 significantly lowered DOX resistance by decreasing cell viability, lowering colony-forming ability, and inducing apoptosis. Moreover, extracellular H19 could be moved to sensitive cells via being incorporated into exosomes. Treating sensitive cells with exosomes from resistant cells increased the chemoresistance of DOX, while downregulation of H19 in sensitive cells abated this effect. Taken together, H19 could be delivered by exosomes to sensitive cells, leading to the dissemination of DOX resistance. Our finding highlights the potential of exosomal H19 as a molecular target to reduce DOX resistance.

Exosome-transmitted miR-567 reverses trastuzumab resistance by inhibiting ATG5 in breast cancer.

Trastuzumab is commonly used in the treatment of human epidermal growth factor receptor-2 positive (HER-2+) breast cancer, but its efficacy is often limited by the emergence of chemoresistance. Recent studies indicate that exosomes act as vehicles for exchange of genetic cargo between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development and progression. However, the specific contribution of breast cancer-derived exosomes is poorly understood. In this study, publicly available expression profiling data from breast cancer and bioinformatics analyses were used to screen potential miRNAs in trastuzumab resistance. A series of gain- or loss-functional assays were performed to define the function of miR-567 and ATG5 in trastuzumab resistance and autophagy, both in vitro and in vivo. Our results showed that miR-567 was significantly decreased in trastuzumab-resistant patients compared with responding patients. Moreover, miR-567 was also downregulated in trastuzumab-resistant cells compared with parental cells. Overexpression of miR-567 reversed chemoresistance, whereas silence of miR-567 induced trastuzumab resistance, both in vitro and in vivo. In addition, enhanced miR-567 could be packaged into exosomes, incorporated into receipt cells, suppressing autophagy and reversed chemoresistance by targeting ATG5. To conclude, exosomal miR-567 plays a key role in reversing trastuzumab resistance via regulating autophagy, indicating it may be a promising therapeutic target and prognostic indicator for breast cancer patients.

Respiratory hyperoxia reverses immunosuppression by regulating myeloid-derived suppressor cells and PD-L1 expression in a triple-negative breast cancer mouse model.

Hypoxia plays an extensive role in the development of the tumor microenvironment (TME), particularly in mediating immunosuppression. Respiratory hyperoxia therapy has the potential to improve the effects of conventional cancer therapies via molecular mechanisms mediating antitumor immunity. Here, we investigated whether hyperoxia therapy can restore tumor immunity and inhibit lung metastases in a mouse model of triple-negative breast cancer (TNBC) by treating a 4T1 mammary carcinoma mouse model with normoxia (21% oxygen) or hyperoxia (60% oxygen) therapy, after tumor development. Using flow cytometry analysis, we observed significant organ-specific expansion of myeloid-derived suppressor cells (MDSCs) and protein expression upregulation of the programmed death-ligand 1 (PD-L1) in the hypoxic TME of 4T1 tumor-bearing mice maintained under normoxia conditions, with the TME converting to a T-cell immune-suppressive state as early as the premetastatic phase. Markedly, hyperoxia treatments ameliorated hypoxia levels in the lung TME and decreased the proportion of MDSCs and the expression of PD-L1 in both the primary tumor and in the metastatic lung, when compared to animals treated with respiratory normoxia therapy. In addition, the number of lung metastatic nodes fell from 90 per lung in the normoxic treated group to 13 per lung in the hyperoxic treated group (P < 0.05), with the latter having limited hyperoxia effects on primary tumor growth (mammary glands). Notably, hyperoxia therapy was characterized by the differential recruitment of CD4+ and CD8+ T-cells. Thus, our study confirms that hyperoxia therapy may be used to overcome TME immunosuppression and control the extend of lung metastases in TNBC. Importantly, changes in immunosuppressive MDSCs frequency and PD-L1 expression levels may serve as biomarkers of hypoxia levels in cancer affected tissues that can benefit from hyperoxia treatments.

ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway.

BACKGROUND: Breast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear. METHODS: The prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model. RESULTS: ACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs. CONCLUSIONS: Our findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway. TRIAL REGISTRATION: Retrospectively registered.

GSTM1 polymorphism in Oncotype DX assay is a potential predictive factor for taxane-based neoadjuvant chemotherapy in estrogen receptor-positive Chinese breast cancer patients.

BACKGROUND: Investigations of the 21-gene Oncotype DX assay in neoadjuvant settings for breast cancer patients are currently underdeveloped. It is still unclear whether any individual gene of the 16 cancer-related genes can be used to predict response to taxane-based neoadjuvant chemotherapy. METHODS: Here, we performed TaqMan RT-PCR reactions to profile the expression patterns of these genes in 66 Chinese ER-positive breast cancer patients' tumor tissues who underwent taxane-based neoadjuvant chemotherapies. Only GSTM1 has distinct non-expression/expression polymorphism, and we observed an almost 2.5-fold increment in the possibility of achieving pathological complete response (pCR) was defined as no histological evidence of residual invasive cancer both in the breast and in the axilla. in GSTM1 non-expression patients. We then analyzed the expression levels of 4 main GST isozymes (GSTA1, GSTT1, GSTP1 and GSTT1) and docetaxel cytotoxicity in various breast cancer cell lines (MCF7, MDA-MB-231, BT474, and SKBR3). Furthermore, we knocked down 4 GST isozymes with siRNA against each isoform in resistant MDA-MB-231. We then observed the changes of docetaxel sensitivity though WST-1 assay, in addition to apoptosis by Hoechst stain and TUNEL assay. RESULTS: Docetaxel IC50 values ranging from 33.0 nM (MDA-MB-231) to 7.20 µM (resistant MDA-MB-231) revealed a close correlation with the expression levels of 4 main GST isozymes. Significantly, depletion of GSTM1 and GSTA1 but not GSTP1 nor GSTT1, suppressed cell viability by 174% and 155% respectively, and was able to induce obvious apoptosis in resistant MDA-MB-132. CONCLUSIONS: Taken together, our results suggest that GSTM1 polymorphism could be useful in the prediction of taxane-based neoadjuvant chemotherapy in ER-positive Chinese breast cancer patients, and that GSTM1 and GSTA1 expression are linked to docetaxel resistance.

miR-506 attenuates methylation of lncRNA MEG3 to inhibit migration and invasion of breast cancer cell lines via targeting SP1 and SP3.

BACKGROUND: Breast cancer has been the first death cause of cancer in women all over the world. Metastasis is believed to be the most important process for treating breast cancer. There is evidence that lncRNA MEG3 functions as a tumor suppressor in breast cancer metastasis. However, upstream regulation of MEG3 in breast cancer remain elusive. Therefore, it is critical to elucidate the underlying mechanism upstream MEG3 to regulate breast cancer metastasis. METHODS: We employed RT-qPCR and Western blot to examine expression level of miR-506, DNMT1, SP1, SP3 and MEG3. Besides, methylation-specific PCR was used to determine the methylation level of MEG3 promoter. Wound healing assay and transwell invasion assay were utilized to measure migration and invasion ability of breast cancer cells, respectively. RESULTS: SP was upregulated while miR-506 and MEG3 were downregulated in breast tumor tissue compared to adjacent normal breast tissues. In addition, we found that miR-506 regulated DNMT1 expression in an SP1/SP3-dependent manner, which reduced methylation level of MEG3 promoter and upregulated MEG3 expression. SP3 knockdown or miR-506 mimic suppressed migration and invasion of MCF-7 and MDA-MB-231 cells whereas overexpression of SP3 compromised miR-506-inhibited migration and invasion. CONCLUSIONS: Our data reveal a novel axis of miR-506/SP3/SP1/DNMT1/MEG3 in regulating migration and invasion of breast cancer cell lines, which provide rationales for developing effective therapies to treating metastatic breast cancers.

Prognostic value of tumor-infiltrating Foxp3+ regulatory T cells in patients with breast cancer: a meta-analysis.

PURPOSE: The prognostic value of tumor-infiltrating Foxp3+ regulatory T cells (Tregs) in breast cancer remains controversial. Therefore, we performed this meta-analysis to determine the impact of Foxp3+ Tregs infiltration on survival outcomes. METHODS: Relevant literature was retrieved from Pubmed, Web of science and Cocohrane until May 30, 2016. Meta-analysis was performed using hazard ratios (HRs), odds ratio (OR) and 95 % confidence intervals (CI) as effect measures. RESULTS: Fourteen studies (10,259 patients) were included. Meta-analysis showed that high Foxp3+ Tregs infiltration was correlated with high histological grade (OR= 2.96, 95%CI [2.03-4.31]), estrogen receptor (ER) negativity (OR= 0.38, 95%CI [0.23-0.60]), human epidermal growth factor receptor type 2 (HER2) positivity (OR=2.43, 95%CI [1.69-3.51]). The detection of FOXP3+ Tregs was significantly associated with recurrence-free survival (RFS) of patients (HR = 1.58, 95 % CI [1.03-2.44]). CONCLUSION: Our meta-analysis suggests that high Foxp3+ Tregs infiltration is associated with poor RFS in breast cancer patients and predicts histological grade, estrogen receptor and HER-2 status.

Endovascular Stent-Graft Placement in Patients with Stanford Type B Aortic Dissection in China: A Systematic Review.

BACKGROUND: Improvements in stent-graft devices and increasing clinical experience with the technique have improved outcomes and expanded clinical indications in patients with Stanford type B aortic dissection (AD) in China. However, the evolution of and modifications to stent grafts have not been reviewed. The aim of this study was to summarize all available published data on technical success, potential benefits, complications, stent evolution, and survival rates associated with endovascular stent-graft placements in patients with Stanford type B AD in China. METHODS: We performed comprehensive searches of the Chinese-language medical literature in Chinese Biomedical Database, China National Knowledge Infrastructure, and Wanfang Data and of the English-language medical literature in PubMed, Web of Science, and the Cochrane Library. This systematic review was based on all retrospective studies assessing outcomes of Stanford type B AD treated with endovascular stent-graft placement in China. RESULTS: A total of 153 retrospective studies that included 8,694 cases were analyzed in this study. Procedure success was reported in 99.7 ± 0.1% of patients. Overall complications were reported in 19.1 ± 0.6% of patients. Postoperative endoleaks occurred in 7.2 ± 0.3% of patients. Major complications were reported in 3.2 ± 0.2% of patients, with a neurological complication rate of 1.3 ± 0.1%. Periprocedural stroke occurred more frequently than did paraplegia (0.8 ± 0.1% vs. 0.1 ± 0.04%). Overall complications were significantly greater in patients treated with first-generation stents than in those treated with second-generation stents (25.1 ± 1.2% vs. 9.5 ± 0.9%, P < 0.001). The in-hospital mortality rate was 1.6 ± 0.1%. In addition, 1.8 ± 0.2% of patients died during a mean follow-up period of 29.4 ± 13.5 months. The Kaplan-Meier estimates of the overall survival rate were 99.0 ± 0.1% at 30 days, 98.5 ± 0.2% at 6 months, 98.4 ± 0.2% at 1 year, 98.1 ± 0.2% at 2 years, and 97.9 ± 0.2% at 5 years. CONCLUSIONS: Endovascular stent-graft placement is feasible and has a high technique success rate as well as favorable neurological complication and survival rates when used to treat Stanford type B AD. The new generation of stent grafts appears to have favorable in-hospital and follow-up outcomes.

[Implantation metastasis of breast cancer in vacuum-assisted breast biopsy needle tract and the impact of neoadjuvant chemotherapy].

OBJECTIVE: To study the incidence of implantation metastasis of breast cancer in vacuum-assisted breast biopsy (VABB) needle tract in Chinese patients and evaluate the effect of neoadjuvant chemotherapy on needle tract metastasis following VABB. METHODS: The breast cancer patients with established diagnosis by VABB were divided into two groups to receive open surgery or neoadjuvant chemotherapy prior to open surgery. The incidence of needle tract metastasis, disease-free survival (DFS) and overall survival (OS) were compared between the two groups. RESULTS: A total of 214 patients were enrolled, among whom 94 directly underwent surgeries and 120 had neoadjuvant chemotherapy before surgery. The two groups showed no significant differences in the incidence of needle tract metastasis (3.2% vs 0.8%, P=0.206), DFS (P=0.221), or OS (P=0.531). CONCLUSION: The incidence of needle tract metastasis is low after VABB, and neoadjuvant chemotherapy does not increase this risk.

Accuracy and axilla sparing potentials of sentinel lymph node biopsy with methylene blue alone performed before versus after neoadjuvant chemotherapy in breast cancer: a single institution experience.

INTRODUCTION: The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping. MATERIALS AND METHODS: Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared. RESULTS: One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary. CONCLUSIONS: Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing.

Pre-treatment hormonal receptor status and Ki67 index predict pathologic complete response to neoadjuvant trastuzumab/taxanes but not disease-free survival in HER2-positive breast cancer patients.

Trastuzumab-containing neoadjuvant chemotherapy achieves a pathologic complete response (pCR) rate of about 40 % in HER2-positive breast cancers, and pCR predicts better survival. A cohort of 102 consecutive Chinese HER2-positive stage II/III patients with neoadjuvant trastuzumab/taxanes were retrospectively analyzed, to evaluate the role of hormonal receptor (HR) status and Ki67 index, along with other parameters, in pCR and survival prediction. pCR rate of the cohort was 44.1 % (45/102). Fifty-three patients were HR-positive and 49 were HR-negative. Median Ki67 index was 40 %, and 49 patients had a high Ki67 index (>40 %) whereas 53 had a low Ki67 index (≤40 %). HR status and Ki67 index were confirmed as the only two parameters associated with pCR in multivariate analysis (hazard ratio = 2.952; 95 % CI, 1.227-7.105; P = 0.016 for HR status and hazard ratio = 2.583, 95 % CI 1.107-6.026, P = 0.028 for Ki67 index). Patients with coexisting HR-negative and high Ki67 index had higher pCR rate (69.2 %), compared to those with either HR-negative alone or high Ki67 alone (hazard ratio = 3.038; 95 % CI, 1.102-8.372; P = 0.029), and to those with coexisting HR-positive and low Ki67 index as well (hazard ratio = 7.071; 95 % CI, 2.150-23.253; P = 0.001). In a median follow-up duration of 25.9 months, 11 disease-free survival events (DFS) were recorded. pCR predicted better DFS (log rank P = 0.018) and was the only significant factor in Cox regression analysis (hazard ratio = 0.184; 95 % CI, 0.038-0.893; P = 0.036). Our study indicates that HR status and Ki67 index are predictors for pCR but not for DFS in HER2-positive patients with neoadjuvant trastuzumab/taxanes, which deserves further investigations.