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BACKGROUND: Coronavirus Disease 2019 (COVID-19) was outbreaking in late 2019 and a proportion of patients developed to pneumonia. Although chest CT is a pivotal diagnostic tool for COVID-19 pneumonia, CT is expensive and also radiological burden for patients. There is urgent to investigate the role of lung ultrasound (LUS) in diagnosing and monitoring COVID-19 pneumonia. METHODS: A total of 8 patients with confirmed cases of COVID-19 pneumonia in Shantou Central Hospital from January 2020 to February 2020 were retrospectively studied. All participants underwent chest HRCT and LUS examination; both were independently performed within 1 day of the other. The radiological patterns were reviewed by 2 radiologists who were blind to the clinical information. A senior ultrasound physician, blind to HRCT results and clinical data, performed bedside LUS in the isolation ward. The CT score was used (a semi-quantitative scoring system) to assess radiographic severity and extent. A B-lines score denoting the extent and severity of sonographic lesion was calculated by summing the number of B-lines on 18 scanning sites. RESULTS: B-lines (100%), pleural irregularities (25%), consolidation (25%), and pleural effusion (25%) were the main findings of LUS examination. Interstitial abnormalities, ground-glass opacities (GGO), consolidations and local or bilateral patchy shadowing were the main findings of HRCT examination. The findings of LUS and HRCT were compared point to point and high consistency was found between the 2 measurements. A significant correlation was also found between the B-lines score and CT score [r=0.96, 95% confidence interval (CI): 0.81 to 0.99, P=0.0001]. CONCLUSIONS: Both LUS patterns and B-lines score are significantly correlated with HRCT findings and score, respectively, supporting its role in assessing COVID-19 pneumonia severity, screening, and following up dynamic changes of pneumonia.

Generative adversarial network (GAN) is one of the most prevalent generative models that can synthesise realistic high-frequency details. However, a mismatch between the input and the output may arise when GAN is directly applied to image super-resolution. To alleviate this issue, the authors adopted a conditional GAN (cGAN) in this study. The cGAN discriminator attempted to guess whether the unknown high-resolution (HR) image was produced by the generator with the aid of the original low-resolution (LR) image. They propose a novel discriminator that only penalises at the scale of the patch and, thus, has relatively few parameters to train. The generator of cGAN is an encoder–decoder with skip connections to shuttle the shared low-level information directly across the network. To better maintain the low-frequency information and recover the high-frequency information, they designed a generator loss function combining adversarial loss term and L1 loss term. The former term is beneficial to the synthesis of fine-grained textures, while the latter is responsible for learning the overall structure of the LR input. The experiments revealed that the proposed method could generate HR images with richer details and less over-smoothness.

Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2−) metastatic breast cancer (MBC). However, there is no evidence of treatment after progression on Ful. Our study aimed to investigate the profile of daily practice regarding therapy after Ful. A consecutive series of 131 HR+, HER2- MBC patients who failed Ful 500 mg as first-line or second-line therapy from June 2014 to June 2017 in 6 institutions were included and analysed. Among 131 patients who failed Ful with similar baseline characteristics, 31 (23.7%) received endocrine therapy (ET), and 100 (76.3%) were treated with chemotherapy (CT). The most frequently applied CT regimen was capecitabine (32%), and the ET regimen was exemestane + everolimus (35.5%). Multivariate analysis showed that patients with bone-only metastasis were associated with lower CT use (OR = 7.97, 95% CI 1.51–41.84, P = 0.01). Among patients who received CT and ET as subsequent treatments, the median progression-free survival (PFS) was 7.5 months (95% CI 6.2–8.8) and 6.0 months (95% CI 4.1–7.9), respectively (p = 0.03). Among patients who were resistant to Ful (PFS

Objective To explore the concepts and practices of advanced breast cancer treatment. Background Metastatic breast cancer (MBC) has become a chronic disease, with a median overall survival (OS) of around 3 years and a 5-year survival rate of about 25%. OS are strongly associated with the best available care, which consists of not only application of guidelines, but also multidisciplinary specialized care, the most efficacious medicines, and so on. Advanced breast cancer (ABC) Guidelines are the most important and authoritative guidelines for MBC. Methods In this review, we demonstrate the history and evolution of the global ABC Guidelines. Since 2015, Chinese multidisciplinary experts have drafted guidelines for clinical diagnosis and treatment of MBC. All of these ABC guidelines describe specialized therapeutic principles for different subtypes MBC in detail. Encouragingly, we have found that some special subtypes are hopeful of being cured, such as HER-2 positive patients with low tumor burden or HR-positive (HR+) MBC with non-visceral metastasis. In our opinion, the definition of cure of MBC is that MBC patients achieve CR and remain for more than five years after systemic treatment, including those with local therapy. Consequently, we also have conducted some researches and meaningful explorations in different subtypes of MBC. In HER2 positive MBC, our study revealed that regular HER2 circulating extracellular domain (ECD) assay can provide the real-time monitoring of tumor burden and prediction of poor outcome, and may present an important opportunity to reassess HER2 status. In HR+ MBC, we suggested that hormone therapy (HT) maintenance is the priority choice for HR+/HER2- MBC after first-line combined chemotherapy. Besides, our real-world study revealed that fulvestrant combined with ovarian suppression was an active option for premenopausal HR+/HER2- MBC. And also, we observed that everolimus (low-dose) combined with hormone therapy was still effective for HR+/HER2- MBC. For mTNBC patients, we found that THA and endostatin exhibited potential efficacy and was well tolerated in pretreated patients. Conclusions Our concepts and practices will contribute to the design of relevant clinical research and accumulation of evidence, and cure of MBC is promising.

Background Invasive micropapillary carcinoma of the breast (IMPC) is a rare pathologic subtype of breast cancer. Since the differences in the pathological features of pure and mixed IMPCs are not fully understood, we aimed to investigate the difference in clinicopathological characteristics between localized pure and mixed IMPCs. Methods A total of 121 localized IMPC cases were included. The clinicopathological features and survival estimates of the pure IMPC and mixed IMPC groups were compared. Targeted sequencing was performed to investigate the genomic profile of paired primary breast cancer and metastatic tissue samples from two pure IMPCs and four mixed IMPCs. Results Overall, 48 cases were pure IMPC and 73 were mixed IMPC. The pure group had a significantly higher proportion of Luminal B compared to the mixed group (37.5% vs. 15.1%). The pure group had a similar HER2 overexpression rate (31.2% vs. 32.9%) and mean age at diagnosis (51.0 vs. 50.2 years), compared with the mixed group. The pure group had a significantly higher proportion of stage IIIC cases compared with the mixed group (38.3% vs. 17.8%). We found no significant difference in the 3-year disease-free survival (DFS) between the two groups (83.7% vs. 80.0%), but the mixed group had a better overall survival (OS) compared with the pure group [HR =0.28 (0.091-0.868), P=0.047]. Conclusions We found that pure IMPC had a more aggressive behavior with locally advanced disease and a higher proportion of Luminal B than mixed IMPC. Mixed IMPC had a longer OS compared to pure IMPC, but there was no significant difference in the 3-year DFS between the two groups.

This study was to investigate the efficacy and safety of fulvestrant 500 mg for the treatment of hormone receptor positive advanced postmenopausal women, including ovarian ablation and investigated factors associated with prolonged time-to-treatment failure. Data from 60 women with metastatic breast cancer who were treated at Zhejiang Cancer Hospital. Patients received 500 mg (n = 60) between December 2011 and November 2012 were followed until November 2017. Main outcomes were clinical responses to fulvestrant, including best response, progressive disease, partial response, and stable disease lasting 12 months or more. Time to progression and time to progression-free-survival were also analyzed. Among the included 60 patients (mean age 47.18 years), 51 (85.0%) had received prior adjuvant therapy. During follow-up after fulvestrant treatment, the median PFS for the best response was derived as 7.0 months (inter-quartile = 4, 13.8 months). The observed median progression-free-survival time for best response was represented longer when fulvestrant was first-line treatment than when patients received prior endocrine and/or chemotherapy. Univariate analysis revealed that receiving either endocrine therapy only or endocrine therapy plus chemotherapy prior to fulvestrant treatment may be associated with median progression-free survival time to best response (P = .002, .026, .007, respectively). Fulvestrant treatment is safe and well-tolerated in women with hormone-sensitive advanced breast cancer, and first-line fulvestrant therapy increases progression-free-survival time, especially in patients without prior adjuvant treatment.

The terahertz spectra of salicylic acid and sodium salicylate are measured by broadband terahertz time-domain spectroscopy (THz-TDS). Two absorption features of salicylic acid and three characteristic features of sodium salicylate are reported for the first time. Our investigation shows that salicylic acid and sodium salicylate can be easily distinguished based on their distinctive THz spectra, which could be attributed to their intra- and intermolecular structure differences. Furthermore, solid-state density functional theory calculations reveal that the absorption features of salicylic acid mainly originate from intermolecular interactions, except for the absorption feature at 2.28 THz, while gaseous-state theory calculations show that the absorption features of sodium salicylate mainly come from intramolecular vibrations except for the absorption feature at 0.40 THz. Our investigation indicates that THz vibrational modes are highly sensitive to molecular structures and intermolecular interactions, promoting the application of THz spectroscopy in distinguishing chemicals and pharmaceuticals with similar molecular structures.

Background One of the major challenges in managing invasive breast cancer (BC) is the lack of reliable biomarkers to track response. Circulating tumor DNA (ctDNA) from liquid biopsy, as a candidate biomarker, provides a valuable assessment of BC patients. In this retrospective study, we evaluated the utility of ctDNA to reflect the efficacy of treatment and to monitor resistance mechanisms. Methods Targeted next‐generation sequencing (NGS) of 416 cancer‐relevant genes was performed on 41 plasma biopsy samples of 19 HER2+ and 12 HER2‐ BC patients. Longitudinal ctDNA samples were analyzed in three BC patients over the treatment course for detecting acquired mutations. Results In HER2+ BC patients, ERBB2 somatic copy numbers in ctDNA samples were significantly higher in patients progressed on HER2‐targeted therapy than those who were still responding to the treatment. Recurrent acquired mutations were detected in genes including ERBB2, TP53, EGFR, NF1, and SETD2, which may contribute to trastuzumab resistance. In longitudinal analyses, the observed mutation allele frequencies were tracked closely in concordance with treatment responses. A novel ERBB2 p.(Leu869Arg) mutation was acquired in one patient upon resistant to trastuzumab therapy, which was further validated as an oncogenic mutation in vitro and contributed to resistance. In HER2‐ BC patients with chemotherapy resistance, genetic alterations on TP53, PIK3CA, and DNA damage repair genes were frequently observed. Conclusions In summary, ctDNA monitoring, particularly longitudinal analyses, provides valuable insights into the assessment of targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2‐ BC patients, respectively., ctDNA molecular alterations in HER2+ patients developed acquired resistance to trastuzumab and Longitudinal analyses of multiple somatic mutations in ctDNA in patients with acquired resistance to trastuzumab.

BACKGROUND: Everolimus (EVE) is an inhibitor of the mammalian target of rapamycin (mTOR) pathway, and it is approved for the treatment of advanced breast cancer (ABC). However, there is still little real-world data on using EVE in Chinese breast cancer patients. We retrospectively analyzed real-world data to determine the factors affecting EVE treatment efficacy and patient outcomes. METHODS: We retrospectively collected the treatment information of ABC patients treated with EVE from 2013 to 2020 in Zhejiang Cancer Hospital. Kaplan-Meier analysis and Cox regression methods were used to calculate and compare the progression-free survival (PFS), and identify the factors associated with EVE treatment efficacy. RESULTS: The study finally enrolled 84 patients meeting the requirement; the median PFS in all 84 patients was 6.87 months. Multivariate analysis showed that liver metastasis [hazard ratio, 1.69; 95% confidence interval (CI), 1.00–2.84; P=0.049], and brain metastasis (hazard ratio, 2.65; 95% CI, 1.07–6.58; P=0.036) were independent risk factors. Subgroup analyses demonstrated EVE + fulvestrant (FUL) was not superior to EVE + aromatase inhibitors (AIs) for PFS (5.77 vs. 7.97 months, P=0.0735). Furthermore, it showed EVE + AI was superior to EVE + FUL in some subgroups: postmenopausal group (hazard ratio, 0.50; 95% CI, 0.26–0.98); without bone metastasis group (hazard ratio, 0.22; 95% CI, 0.06–0.80); visceral disease group (hazard ratio, 0.37; 95% CI, 0.20–0.69). CONCLUSIONS: EVE combined with endocrine therapy is an effective treatment option for Chinese patients with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) breast cancer, although EVE + FUL was not superior to EVE + AI. Liver metastasis and brain metastasis were independent risk factors for successful EVE + endocrine therapy.

BACKGROUND: Palbociclib combined with endocrine therapy has been approved as a front-line treatment for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment. METHODS: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR) as detected by immunohistochemistry in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS). RESULTS: In the total population, women with Ki67 ≥14% had marginally significantly shorter PFS than those with Ki67

Background: Endocrine therapy(ET) and Chemotherapy(CT) are used as standard maintenance therapy for HR+ and HER2- metastatic breast cancer(MBC) in clinical practice. There was no prospective study data on which is better. In OVERSTEP, we provide some strong evidence for clinical practice. Methods: OVERSTEP(NCT02597868) is a multicenter, randomized, open-label, prospective clinical trial that enrolled 181 patients in China. patients aged 18-70 years without chemotherapy for ABC/MBC previously, histologically confirmed metastatic HR+ and HER2- breast cancer, and ECOG performance status of 0-1. These patients were received capecitabine plus another chemotherapy drug as 1st-line salvage chemotherapy at least 4 cycles. The patients response are CR, PR and SD carried maintenance treatment next, randomly assigned (1:1) to receive either capecitabine single or endocrine therapy. Randomization was done centrally with stratification by endocrine resistance and visceral metastasis. The primary endpoint was progression-free survival(PFS) and analyses were base on all patients who received at least one dose maintenance therapy. We take superiority test in the 2 groups. Results: 136(75.14%) patients were randomized after combined chemotherapy to capecitabine single or endocrine therapy groups for maintenance treatment. 45(24.86%) patients are progress disease (PD) after combined chemotherapy. After a median follow-up of 24.3 months (IQR 20.46-37.25 ) in the endocrine maintenance therapy group and 24.1 months(IQR 20.67-36.77) in the Capecitabine maintenance therapy group ,the hazard ratio for PFS was 0.625(95%CI 0.429-0.909 P=0.013),Median PFS was 17.5 months(95%CI 11.544-23.856) in endocrine maintenance therapy group and 12,2 months(95%CI 11.170-13.230) in capecitabine maintenance therapy group. In endocrine sensitive group, the hazard ratio for PFS was 0.515(95%CI0.269-0.988 P=0.042), Median PFS was 29.3 months(95%CI 14.605-43.995) in endocrine maintenance therapy group and 14.8 months(95%CI 7.445-22.155) in capecitabine maintenance therapy group. In endocrine resistance group, the hazard ratio for PFS was 0.791(95%CI 0.499-1.253 P=0.314), Median PFS was 13.6 months(95%CI 9.111-18.089) in endocrine maintenance therapy group and 12.0 months(95%CI10.357-13.643) in capecitabine maintenance therapy group. In visceral metastasis group, the hazard ratio for PFS was 0.668(95%CI0.410-1.089 P=0.101), Median PFS was 14.3 months(95%CI 11.113-17.487) in endocrine maintenance therapy group and 11.0 months(95%CI 8.140-13.860) in capecitabine maintenance therapy group. In non-visceral metastasis group, the hazard ratio for PFS was 0.54(95%CI0.300-0.972 P=0.037), Median PFS was 25.3 months(95%CI 15.278-35.322) in endocrine maintenance therapy group and 17.0months(95%CI 10.783-23.217) in capecitabine maintenance therapy group. Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, ET maintenance has a better survival benefits than CT,especially for ET-sensitive and non-visceral involved cases. So ET maintenance is the first choice for ABC/MBC after 1st-line combined chemotherapy. Citation Format: Jian Huang, Xiying Shao, Li Cai, Yanxia Shi, Zhanhong Chen, Ping Huang, Yongmei Yin, Lili Zhang, Peng Shen, Wenming Cao, Weiwu Ye, Yuan Huang, Caijin Lou, Lei Lei, Yabin Zheng, Weibin Zou, Junqing Chen, Xiaojia Wang. Primary analysis of OVERSTEP: A multicenter, randomized clinical trial of capecitabine or endocrine therapy as a maintenance therapy after the 1st-line chemotherapy in hormone receptor positive and HER2-negative advanced/metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-01.

// Ping Huang 1 , Shujun Dai 2,* , Zhimin Ye 3 , Yajuan Liu 4 , Zhanhong Chen 1 , Yabing Zheng 1 , Xiying Shao 1 , Lei Lei 1 and Xiaojia Wang 1 1 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China 2 Department of Intense Care Unit, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 3 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China 4 Department of Tumor Comprehensive Treatment, Hangzhou Cancer Hospital, Hangzhou, China * Co-first author Correspondence to: Zhimin Ye, email: // Xiaojia Wang, email: // Keywords : breast cancer; Her-2; LVEF; trastuzumab; cardiac event Received : June 29, 2016 Accepted : November 14, 2016 Published : November 30, 2016 Abstract We examined the long-term clinical tolerance and cardiac safety of trastuzumab treatment in ninety-four female patients diagnosed with breast cancer with human epidermal growth factor receptor 2 (HER-2) overexpression. Electrocardiography (ECG) was monitored throughout trastuzumab treatment, and left ventricular ejection fractions (LVEFs) were estimated using echocardiography prior to treatment with trastuzumab and every 3 months after its first application. The duration of trastuzumab treatments ranged from 3 to 60 months. Declines in LVEF ≥ 15% were seen mainly after 3-15 months of trastuzumab treatment, and LVEF was lowest at 15 months, which coincided with the largest decline in LVEF from baseline. Spearman correlation coefficients indicated that accumulation of anthracycline, the use of cyto/cardioprotective drugs (CPD) and the duration of trastuzumab treatment were all associated with the change of LVEF, and there was a strong correlation between these factors and the change of LVEF (ρ=0.81, ρ=0.734 and ρ=0.777 respectively). These results indicate that significant decreases of LVEF may be seen after 3-15 months of trastuzumab treatment, but that there is a favorable benefit-risk ratio for patients undergoing long-term trastuzumab treatment.

The aim of the present study was to establish the underlying regulatory mechanism of estrogen receptor (ER) in breast cancer cell gene expression. A gene expression profile (accession no. GSE11324) was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) from an estrogen treatment group and a control group were identified. Chromatin immunoprecipitation with high‑throughput sequencing data (series GSE25710) was obtained from the GEO for the ER binding sites, and binding and expression target analysis was performed. A total of 3,122 DEGs were obtained and ER was demonstrated to exhibit inhibition and activation roles during the regulation of its target gene expression. Motif analysis revealed that the upregulated target genes that demonstrated interactions with ER were meis homeobox 1 (MEIS1) and forkhead box P3 (FOXP3). The downregulated target genes, which demonstrated interactions with ER, were thyroid hormone receptor, β (THRB) and grainyhead‑like 1 (GRHL1). Thus, it was observed that ER stimulated gene expression by interacting with MEIS1 and FOXP3, and ER inhibited gene expression by interacting with THRB and GRHL1. However, additional experiments are required to provide further confirmation of these findings.

Huanhuan Zhou,1 Kongbeng Lu,2 Lei Zheng,1 Liwei Guo,3 Yun Gao,1 Xianyuan Miao,1 Zhanhong Chen,1 Xiaojia Wang1 1Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Medical Oncology, Shaoxing Second Hospital, Shaoxing, Zhejiang, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Purpose: To explore the prognostic significance of mammary Paget’s disease (PD) in breast cancer (BC) patients and to investigate the association between clinical manifestation and outcome in invasive ductal carcinoma patients with PD (PD-IDC). Patients and methods: Eighty-five patients diagnosed with mammary PD with underlying BC from 2006 to 2012 at Zhejiang Cancer Hospital were recruited. A matched group comprised 85 patients diagnosed with BC without PD. Patients were matched according to four variables: stage (0–IV), age at diagnosis (within 5 years), histologic subtype, and the year of surgery. The 74 patients diagnosed with PD-IDC were divided into three groups based on their clinical presentation. Results: Compared with the matched group, the PD group had more HER2 positivity (P

MicroRNAs are emerging as critical regulators of the initiation and progression of multiple types of human cancers, including breast cancer. In the present study, the expression of miR-181b in breast cancer patient serum and breast cancer cell lines was evaluated. It was demonstrated that the miR-181b level was significantly upregulated in patient serum and breast cancer cell lines compared with that in normal controls. The results of in vitro 3H thymidine incorporation and Transwell migration assay indicated that miR-181b overexpression markedly promoted the proliferation and metastasis of breast cancer cells. These data suggest that miR-181b is a tumor promoter in breast cancer. Furthermore, miR-181b expression was found to be upregulated in doxorubicin (DOX)-resistant T-47D cells (T-47D-R) compared with that in the parental T-47D cells, and upregulation of miR-181b expression decreased the anticancer effect of DOX in the T-47D cells. Mechanistic studies demonstrated that the Bim gene, an essential initiator of apoptosis, was inhibited by miR-181b overexpression. We observed that knockdown of miR-181b by its specific inhibitors significantly re-sensitized the T-47D-R cells to the cytotoxicity of DOX. Importantly, we demonstrated that miR-181b inhibitors increased the level of Bim in the T-47D-R cells, resulting in the loss of mitochondrial membrane potential (MMP) and the activation of caspases caused by DOX. In summary, the results of the present study suggest that miR-181b functions as an oncogene during breast cancer development, and the miR-181b/Bim pathway may be a novel target used to overcome the chemoresistance in breast cancer.

The aim of the present study was to investigate the immunohistochemical expression of cluster of differentiation (CD) 34 and vascular endothelial growth factor (VEGF) in breast cancer tissue, and their prognostic significance. High CD34 expression levels (microvessel density, >15/HPF) were identified in 27.3% (12/44) of cases, exhibiting no significant correlation with the clinicopathological characteristics of the patients. However, Kaplan-Meier analysis demonstrated that the survival time of patients with high CD34 expression was significantly shorter than that of patients with low CD34 expression (50.0 vs. 90.6%; P=0.003). Samples with high VEGF expression levels (++ or +++) accounted for 63.6% (28/44) of the total number of cases. High VEGF expression was significantly prevalent in patients aged ≥50 years compared with patients aged

Triple negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer cases and is usually more aggressive with a poorer clinical outcome compared with other breast cancer subtypes. Evidence of the involvement of microRNAs (miRNAs) in cancer has provided an opportunity for the development of novel effective therapeutic targets in TNBC. In the present study, the miRNA expression profiles of the human breast cancer cell line, MDA-MB-231, and MCF-7 cells, was evaluated by using miRNA microarray analysis. A total of 107 differentially expressed miRNAs (57 upregulated and 50 downregulated) were identified in MDA-MB-231 cells compared with MCF-7 cells. Five prominently dysregulated miRNAs (miR-200c-3p, miR-221-3p, miR-222-3p, miR-192-5p and miR-146a) were further confirmed by reverse transcription-quantitative polymerase chain reaction. In addition, gene ontology analysis and pathway enrichment analysis revealed that the dysregulated miRNAs and predicted targets were found to be involved in the mitogen-activated protein kinase, Wnt, and transforming growth factor-β signaling pathways, which were known to contribute to TNBC progression and metastasis. Finally, miRNA gene network analyses suggested that miR-200c may serve as a crucial miRNA in breast cancer. Taken together, these findings may provide a comprehensive view of the function of aberrant miRNAs involved in TNBC, and dysregulated miRNAs hold promise as potential biomarkers and therapeutic targets for patients with TNBC.

It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the CYP19A1 rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of CYP19A1 rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for CYP19A1 rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment.

Rationale: Breast cancer is the most prevalent malignancy in women worldwide. Our patient presented with a history of breast liposarcoma (LPS) and was found to have pleural metastasis during the initial workup. Patient concerns: The patient was complaining about chest pain and dyspnea that had persisted for a week. Diagnoses: After a full evaluation and histological diagnosis, she was diagnosed as metastatic breast LPS. Interventions: We adopted 6 cycles of pegylated liposomal doxorubicin (PLD) plus ifosfamide as 1st-line palliative chemotherapy, combined with local pleural effusion management. Outcomes: The patient's symptoms were notably relieved, and both malignant metastatic lesions and pleural effusion were controlled. Lessons: Although metastatic breast LPS is rarely reported and incurable, more clinical experience and use of next-generation sequencing should be helpful in finding the effective treatment for metastatic LPS.

Purpose: The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer. Methods: Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). Results: Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P = 0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P = 0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P = 0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P = 0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P = 0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P = 0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P = 0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P = 0.013). Conclusions: The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to screen serum samples to identify protein markers for early breast cancer relapse. We collected 67 serum samples from patients with breast cancer (24 preoperative; 23 postoperative without breast cancer relapse; 20 postoperative with breast cancer relapse). Eight protein peaks varied between the presurgical group and the postsurgical group without breast cancer relapse; 4 protein peaks were differentially expressed between the postsurgical patients without relapse and patients with relapse. The peak at 3964 m/z dropped after surgery and rebounded after relapse (P < 0.01). These results indicate that there are differences in serum protein expression among the three different groups of patients. SELDI-TOF MS could be used to screen blood samples for the early detection of relapse in primary breast cancer patients. Specifically, protein peak at 3964 m/z is a potential biomarker for the detection of early breast cancer relapse. Anat Rec, 2011. © 2011 Wiley-Liss, Inc.

Context: Breast cancer becomes more prevalent with advancing age. The increased risk of breast cancer needs to be considered when choosing a treatment plan and a kind of detection method for the postmenopausal woman. Better breast cancer prognostication may improve selection of patients for adjuvant therapy. Aims: The aim of this study is to investigate the role of serum protein peak 3144 m/z in postmenopausal breast cancer patients, whether if it could be used as a potential prognostic tool. Settings and Design: Two hundred and two postmenopausal breast cancer patients were involved in this retrospective study at Zhejiang Cancer Hospital. Subjects and Methods: Serum level of protein peak 3144 m/z was assessed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Statistical Analysis Used: Prognostic factors were compared across subgroups of patients depending on the protein peak 3144 m/z levels by Chi-square test. The log-rank test was used to compare survival curves, and Cox proportional hazards regression analysis was performed to identify prognostic factors. Results: The percentage of cases with higher 3144 m/z protein peak was 32.7% (66/202) in postmenopausal breast cancer patients. The serum protein peak 3144 m/z was positively related to lymph node metastasis. Patients with higher protein peak 3144 m/z had significantly poorer overall survival compared with patients with lower serum protein peak 3144 m/z ( P = 0.0053). Multivariate regression analysis also revealed that protein peak 3144 m/z was an independent prognostic factor in postmenopausal breast cancer patients (borderline, P = 0.064). Conclusions: The protein peak 3144 m/z was a potential prognostic factor, and it could be used as a prognostic monitoring tool in postmenopausal breast cancer patients.