The Value of Neoadjuvant Anthracycline-Based Regimens for HER2-Positive Breast Cancer: A Systematic Review and Meta-analysis Including 1366 Patients.

Background: The standard recommendation for neoadjuvant therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer patients is trastuzumab in combination with chemotherapy, but there is no current standard recommendation for appropriate chemotherapy regimens. This meta-analysis evaluated the efficacy and cardiac safety of the concurrent use of anti-HER2 targeted drugs and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancers. Methods: The pooled odds ratio (OR) rate for pathologic complete response (pCR), the pooled hazard ratio (HR) of overall survival (OS), and the left ventricular ejection fraction (LVEF) decline events were all calculated. Differences in efficacy, prognosis, and cardiac safety were compared between patients receiving an anthracycline-containing regimen (AB) and those treated with non-anthracycline-based (nAB) NAC. Results: A total of 1366 patients in 4 prospective and 3 retrospective studies were included in the meta-analysis. The pooled OR for pCR rate was 0.73 with a 95% confidence interval (CI) of 0.43 to 1.24 (P = .246). Subgroup analysis of low tumor burden cases showed no improvement in pCR rate for patients in the AB group compared with nAB, with the pooled OR rate being 0.73 with a 95% CI of 0.37 to 1.44 (P= .357). The 3-year OS rate was 95.63% and 95.54% in the AB and nAB groups, respectively, with no statistical difference (P= .157). There was a significant increase in the rate of LVEF decline of 19.07% in the AB group compared with 13.33% for the nAB group, with an HR of 1.62 and a 95% CI of 1.11 to 2.36 (P = .013). Conclusions: The addition of anthracyclines did not improve pCR rates and survival after neoadjuvant and the increased cardiotoxicity of anthracyclines further limited their application. This study showed that it was feasible to use anti-HER2 drugs without anthracyclines in neoadjuvant therapy for HER2-positive breast cancer patients.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

INTRODUCTION: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer (ClinicalTrials.gov identifier: NCT03756064). METHODS: Sixty-nine women with HER2-positive early (T1-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) were recruited from October 1, 2019, to June 1, 2021. Before surgery, patients received 6 cycles of orally pyrotinib (400 mg once per day), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), docetaxel (75 mg/m2), and carboplatin (AUC = 6 mg/mL·min) or orally placebo, trastuzumab, and docetaxel, and carboplatin every 3 weeks. The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by age, hormone receptor status, tumor stage, nodal status, cTNM stage, and Ki-67 level was used to compare rates between treatment groups. RESULTS: In total, 69 female patients were randomized (pyrotinib, 36; and placebo, 33; median age, 53 [31-69] years). In the intention-to-treat population, total pathologic complete response rates were 65.5% (19/29) in the pyrotinib group and 33.3% (10/30) in the placebo group (difference, 32.2%, p = 0.013). Diarrhea was been reported in 86.1% of patients (31/36) in the pyrotinib group as the most common adverse events (AEs) and 15.2% of patients (5/33) in the placebo group. But no grade 4 or 5 AEs were reported. CONCLUSION: Treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin resulted in a statistically significant improvement in the total pathologic complete response rate versus placebo, trastuzumab, docetaxel, and carboplatin for the neoadjuvant treatment of HER2-positive early or locally advanced breast cancer in Chinese patients. Safety data were in line with the known pyrotinib safety profile and generally comparable between treatment groups.

Long non-coding RNAs in breast cancer stem cells.

Breast cancer, one of the most commonly diagnosed cancers worldwide, is a heterogeneous disease with high rates of recurrence and metastasis that contribute to its high mortality rate. Breast cancer stem cells (BCSCs) are a small but significant subset of heterogeneous breast cancer cells that possess stem cell characteristics such as self-renewal and differentiation abilities that may drive metastasis and recurrence. Long non-coding RNAs (lncRNAs) are a class of RNAs that are longer than 200 nucleotides in length and do not possess protein-coding properties. An increasing number of studies have shown that some lncRNAs are abnormally expressed in BCSCs, and have great biological significance in the occurrence, progression, invasion, and metastasis of various cancers. However, the importance of lncRNAs, as well as the molecular mechanisms that regulate and promote the stemness of BCSCs, are still poorly understood. In the current review, we aim to summarize recent studies that highlight the role of lncRNAs in tumor occurrence and progression through BCSCs. In addition, the utility of lncRNAs as biomarkers of breast cancer progression, and their potential use as therapeutic targets for treatment of breast cancer, will be discussed.

Study of lncRNA TPA in Promoting Invasion and Metastasis of Breast Cancer Mediated by TGF-ß Signaling Pathway.

PURPOSE: This study was to investigate the effects of lncRNA TPA overexpression and knockdown in stable transfected cell lines on the EMT, migration and invasion capabilities of breast cancer cells. METHODS: WB and qRT-PCR were used to detect the expression of E-cadherin, Vimentin, fibronectin and N-cadherin, the key molecules of EMT, to determine whether lncRNA regulates EMT; scratch, migration and invasion assay were used to detected the effect of lncRNA TPA on the migration and invasion of breast cancer cells. The effect of lncRNA TPA on breast cancer metastasis was observed in nude mice model. Pierce Magnetic RNA-Protein Pull-Down Kit was used to bind the 3'-terminal desulfurized biotin-labeled lncRNA TPA with Magnetic beads, and then incubated with the proteins extracted from cell line C and D, respectively. After elution of the binding proteins, the interacting proteins were further identified by mass spectrometry to screen out the interacting proteins. The candidate proteins were expressed and purified in vitro, and the interaction between lncRNA-candidate proteins were verified by RNA-EMSA. RESULTS: Overexpression of lncRNA TPA decreased the expression of E-cadherin, and significantly increased the expression of Vimentin, fibronectin and TGF-ß1 (p < 0.01), and increased the migration rate, migration ability and invasion ability of cell group (P < 0.01). Multiple lung metastases were observed in the lung tissue of nude mice with overexpression of lncRNA TPA. CONCLUSION: LncRNA TPA affects the occurrence of breast cancer EMT through TGF-ß signaling pathway, and then promotes the invasion and metastasis of breast cancer. LncRNA TPA may affect the corresponding signaling pathways through one or more interacting proteins, and ultimately promote the invasion and metastasis of breast cancer.

Identification of a 6-gene signature for the survival prediction of breast cancer patients based on integrated multi-omics data analysis.

PURPOSE: To identify a gene signature for the prognosis of breast cancer using high-throughput analysis. METHODS: RNASeq, single nucleotide polymorphism (SNP), copy number variation (CNV) data and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), and randomly divided into training set or verification set. Genes related to breast cancer prognosis and differentially expressed genes (DEGs) with CNV or SNP were screened from training set, then integrated together for feature selection of identify robust biomarkers using RandomForest. Finally, a gene-related prognostic model was established and its performance was verified in TCGA test set, Gene Expression Omnibus (GEO) validation set and breast cancer subtypes. RESULTS: A total of 2287 prognosis-related genes, 131 genes with amplified copy numbers, 724 gens with copy number deletions, and 280 genes with significant mutations screened from Genomic Variants were closely correlated with the development of breast cancer. A total of 120 candidate genes were obtained by integrating genes from Genomic Variants and those related to prognosis, then 6 characteristic genes (CD24, PRRG1, IQSEC3, MRGPRX, RCC2, and CASP8) were top-ranked by RandomForest for feature selection, noticeably, several of these have been previously reported to be associated with the progression of breast cancer. Cox regression analysis was performed to establish a 6-gene signature, which can stratify the risk of samples from training set, test set and external validation set, moreover, the five-year survival AUC of the model in the training set and validation set was both higher than 0.65. Thus, the 6-gene signature developed in the current study could serve as an independent prognostic factor for breast cancer patients. CONCLUSION: This study constructed a 6-gene signature as a novel prognostic marker for predicting the survival of breast cancer patients, providing new diagnostic/prognostic biomarkers and therapeutic targets for breast cancer patients.

Machine Learning-Based Radiomics Nomogram Using Magnetic Resonance Images for Prediction of Neoadjuvant Chemotherapy Efficacy in Breast Cancer Patients.

Purpose: The construction and validation of a radiomics nomogram based on machine learning using magnetic resonance image (MRI) for predicting the efficacy of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BCa). Methods: This retrospective investigation consisted of 158 patients who were diagnosed with BCa and underwent MRI before NACT, of which 33 patients experienced pathological complete response (pCR) by the postoperative pathological examination. The patients with BCa were divided into the training set (n = 110) and test set (n = 48) randomly. The features were selected by the maximum relevance minimum redundancy (mRMR) and absolute shrinkage and selection operator (LASSO) algorithm in the training set. In return, the radiomics signature was established using machine learning. The predictive score of each patient was calculated using the radiomics signature formula. Finally, the predictive scores and clinical factors were used to perform the multivariate logistic regression and construct the nomogram. Receiver operating characteristics (ROC) analyses were used to assess and validate the diagnostic accuracy of the nomogram in the test set. Lastly, the usefulness of the nomogram was confirmed via decision curve analysis (DCA). Results: The radiomics signature was well-discriminated in the training set [AUC 0.835, specificity 71.32%, and sensitivity 82.61%], and test set (AUC 0.834, specificity 73.21%, and sensitivity 80%). Containing the radiomics signature and hormone status, the radiomics nomogram showed good calibration and discrimination in the training set [AUC 0.888, specificity 79.31%, and sensitivity 86.96%] and test set (AUC 0.879, specificity 82.19%, and sensitivity 83.57%). The decision curve indicated the clinical usefulness of our nomogram. Conclusion: Our radiomics nomogram showed good discrimination in patients with BCa who experience pCR after NACT. The model may aid physicians in predicting how specific patients may respond to BCa treatments in the future.

The treatment option of progressive disease in breast cancer during neoadjuvant chemotherapy: a single-center experience.

Patients' responses to breast cancer neoadjuvant chemotherapy (NACT) differ because of heterogeneous tumor characteristics. Reports about NACT progression are sporadic. Here we enrolled 1187 patients who received NACT in our cancer center between January 1, 2007, and December 31, 2016. We analyzed the characteristics and treatments of patients with progressive disease (PD) or non-PD or pathological complete response (pCR). In total, 45 (3.8%) patients had PD. PD patients were associated with a significantly worse disease-free survival (DFS) (hazard ratio (HR) = 3.77; 95% CI, 1.77 to 8.00; P =.001) and overall survival (OS) (HR = 3.85; 95% CI, 1.77 to 8.35; P =.001). For the PD patients, 28 (62.2%) patients received mastectomy immediately after PD, and 17 (37.8%) changed to chemotherapy. DFS and OS exhibited no significant differences between these two salvage therapies. After a change to second chemotherapy, 58.8% (10/17) patients had PD or SD. With the exception of tumor size, pretreatment T stage, and histology type, no other significant differences were noted between PD and pCR patients. Our results demonstrated that PD patients were associated with a significantly worse prognosis. Based on these results, we suggest to give the addition of trastuzumab to HER-2 positive patients instead of changing the chemotherapy regimen and proceeding to surgery instead of further chemotherapy once patients have PD during NACT. Given that some similar characteristics exist between PD and pCR patients, more studies to identify novel molecular markers to predict disease response to NACT should be performed.

Does dose-dense neoadjuvant chemotherapy have clinically significant prognostic value in breast cancer?: A meta-analysis of 3,724 patients.

PURPOSE: Neoadjuvant chemotherapy (NCT) is typically the initial treatment for non-early breast cancer patients. We thereby conducted a meta-analysis to explore whether dose-dense neoadjuvant chemotherapy (ddNCT) improved the long-term prognosis of patients compared to the standard NCT regimen. METHODS: We compared the differences in efficacy and prognosis between patients receiving standard NCT and ddNCT. We also calculated the pooled odds ratio (OR) of pathological complete response (pCR) and the pooled hazard ratio (HR) of overall survival (OS) and disease-free survival (DFS). RESULTS: Nine randomized controlled trials involving 3,724 patients from 10 published studies were included in the meta-analysis. The pooled OR for ddNCT was 1.18 (95% confidence interval (CI): 0.83-1.67, P = 0.356). A subgroup analysis in the cases with low hormone receptor expression levels showed the pCR in patients undergoing ddNCT was significantly higher than the pCR in patients undergoing standard NCT (OR = 1.36, 95% CI: 1.09‒1.69, P = 0.007). There was no significant difference in DFS and OS between ddNCT and standard NCT (DFS: HR = 0.90, 95% CI: 0.79‒1.02, P = 0.095; OS; HR = 0.91, 95% CI: 0.81‒1.04, P = 0.160), regardless of hormone receptor expression levels. These data suggested the higher pCR rate in patients receiving ddNCT did not result in a survival benefit. CONCLUSIONS: The meta-analysis demonstrated that ddNCT can significantly improve the pCR rate in patients with low hormone receptor expression levels, although patient survival was not significantly improved. The ddNCT can increase the breast-conserving rate and reduced pre-operative waiting time without increasing adverse reactions. This regimen can be considered when developing an NCT plan.

Impact on survival of estrogen receptor, progesterone receptor and Ki-67 expression discordance pre- and post-neoadjuvant chemotherapy in breast cancer.

PURPOSE: To investigate whether estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression discordance before and after neoadjuvant chemotherapy (NAC) correlates with prognosis and treatment of breast cancer patients. METHODS: The study cohort included 482 breast cancer patients at the Zhejiang Cancer Hospital from January 1, 2008, to December 31, 2018. Core needle biopsies and excised tissue biopsies pre- and post-NAC were obtained. Immunohistochemistry was used to determine ER, PR and Ki-67 status. The relationship between biomarker discordance before and after NAC and clinicopathological features was compared retrospectively. RESULTS: ER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-NAC. Discordance in the three markers pre- and post-NAC was observed in 50 (10.4%), 82 (17.0%) and 373 (77.4%) cases, respectively. Positive-to-negative PR expression changes were the most common type of discordance observed. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than for patients with stable PR expression. The risk of death in patients with increased Ki-67 expression following NAC treatment was 2.05 times greater than for patients with stable Ki-67 expression. CONCLUSION: Breast cancer patients showed changes in ER, PR and/or Ki-67 status throughout NAC, and these changes possibly influenced disease-free survival and overall survival. A switch to negative hormone receptor expression with increased Ki-67 expression following NAC could be indicators of a worse prognosis. Biomarker expression investigations following NAC may potentially improve patient management and survival.

Associations between folate metabolism enzyme polymorphisms and breast cancer: A meta-analysis.

We performed this meta-analysis to explore associations between folate metabolism enzyme polymorphisms and breast cancer (BC) in a larger pooled population. Systematic literature research was performed to identify eligible studies for pooled analyses. Totally 92 genetic association studies were included for analyses. The pooled analyses revealed significant findings for MTRR rs1801394 polymorphism in South Asians, for MTR rs1805087 polymorphism in Caucasians and East Asians, and for MTHFR rs1801133 polymorphism in East Asians. In conclusion, the present meta-analysis indicated that MTRR rs1801394, MTR rs1805087, and MTHFR rs1801133 polymorphisms could be used to identify individuals at high risk of developing BC.

Matrine suppresses breast cancer metastasis by targeting ITGB1 and inhibiting epithelial-to-mesenchymal transition.

Metastasis can be a fatal step in breast cancer progression. Effective therapies are urgently required due to the limited therapeutic options clinically available. The aim of the present study was to investigate the effect of matrine (MAT), a traditional Chinese medicine, on the proliferation and migration of human breast cancer cells and its underlying mechanisms of action. The proliferation of MDA-MB-231 cells was inhibited and apoptosis was induced following treatment with MAT, as determined by MTT and Annexin-V-FITC/PI assays. Western blot analysis was used to detect the LC-3II/I levels and the results suggested that tumor autophagy is involved in the anti-tumor activity of MAT. To the best of our knowledge, this is the first study to report that MAT inhibits MDA-MB-231 and MCF-7 cell motility, potentially by targeting integrin ß1 (ITGB1) and epithelial-to-mesenchymal transition (EMT), as indicated by Transwell® and siRNA interference assays. In conclusion, ITGB1 and EMT are involved in MAT-induced breast carcinoma cell death and the inhibition of metastasis. This may lead to the development of novel compounds for the treatment of breast cancer metastasis.

Prognosis and endocrine therapy selection for patients with low hormone receptor-positive breast cancer following neoadjuvant chemotherapy: A retrospective study of 570 patients in China.

The 2010 American Society of Clinical Oncology guidelines have reduced the immunohistochemistry cut-off value for determining estrogen receptor b positivity from 10 to 1% of stained cells in breast cancer. In clinical practice, low-hormone receptor positive (low HR+) tumors are classified in the luminal subtype, although they exhibit aggressive features and poor prognosis. Information regarding the prognosis of patients with breast cancer following treatment with optimal endocrine therapy and neoadjuvant chemotherapy (NAC) is currently lacking. In the present study, the differences in clinical characteristics and survival of patients with breast cancer were compared among those with low and high HR+ breast cancer who received NAC. Furthermore, the effects of different types of endocrine therapies on the prognosis of patients with breast cancer were compared. The study population comprised patients with primary breast cancer who were treated at the Zhejiang Cancer Hospital between January, 2007 and December, 2017. Patients were divided into three groups based on the results of immunohistochemistry: HR+ (positive staining >10%), HR- (positive staining <1%) and low HR+ (positive staining 1-10%). The low HR+ group was further divided into three subgroups according to the different endocrine therapies administered: Tamoxifen, aromatase inhibitor or no treatment. Among the 570 patients included in the present study, 60 (10.53%) patients had low HR+ tumors. With a median follow-up of 48.98 months, patients with low HR+ tumors had reduced survival rates compared with those with HR+ tumors. Furthermore, the pathologic complete response rate (pCR) of patients with low HR+ was comprised between pCR from patients with HR+ and pCR from patients with HR- following NAC treatment. In addition, no significant difference in the overall prognosis was observed among patients with low HR+ following treatment with different endocrine therapies. Subsequently, patients in the low HR+ group were more likely to benefit from NAC compared with patients in the HR+ group. Intensive endocrine therapy may therefore improve the prognosis of patients with breast cancer and low HR+; however, further investigation is required.

Deleterious Mutations in DNA Repair Gene FANCC Exist in BRCA1/2-Negative Chinese Familial Breast and/or Ovarian Cancer Patients.

Introduction: FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China. Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation. Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients. Conclusion: FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer.

Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future.

Breast carcinoma associated with prolactinoma: A case report.

We report a 28-year-old woman who presented with a 6-year history of milk-like discharge from both of her nipples and was diagnosed with prolactinoma based on computed tomography (CT) findings and serum prolactin level. Further breast examination revealed a mass located in the upper outer region of the left breast. She underwent subtotal pituitary tumor resection. Thereafter, modified radical mastectomy was performed for left breast cancer. Twelve years after treatment, prolactinoma recurrence was detected, and bromocriptine therapy was administered. No recurrence of breast cancer was discovered. Based on this case report, we stress the importance of prolactin levels due to their possible biologic effects on breast cancer induction or growth.

INFα-2b inhibitory effects on CD4(+)CD25(+)FOXP3(+) regulatory T cells in the tumor microenvironment of C57BL/6 J mice with melanoma xenografts.

BACKGROUND: Regulatory T cells (Tregs), particularly the CD4(+)CD25(+)Foxp3(+) Tregs, down regulate immunity and promote tumor cell growth by directly suppressing CD8(+) and CD4(+) T cells. Alternatively they can promote tumor growth by generating interleukin-10 (IL-10) and transforming growth factor ß (TGFß) in situ, which help tumor cells to evade the immune system. METHODS: In vivo tumor models were prepared via subcutaneous injection with a suspension of B16 melanoma cells into the left upper flank of C57BL/6 J mice. The mice were randomized into five groups: radiotherapy (RT), chemotherapy (CT), radiochemotherapy (RCT), Inteferon α (INFα) groups, and a control group. Flow cytometry was used to determine the Tregs levels in the spleen and peripheral blood, and immunohistochemistry was performed to determine the expression levels of TGFß and IL-10 in the tumor microenvironment. RESULTS: Tumor weight was significantly reduced in the CT or RCT groups (40.91 % and 41.83 %, respectively), while the reduction in tumor weight was relatively lower for the RT and IFNα groups (15.10 % and 13.15 %, respectively). The flow cytometry results showed that the ratios of CD4(+)CD25(+)Foxp3(+) Tregs to lymphocytes and CD4(+) cells in the spleen and in peripheral blood were significantly decreased after treatment with IFNα (P < 0.05). Expression of TGFß and IL-10 in the tumor microenvironment in the CT and RT groups was higher compared with the control group (P < 0.01), while the expression of TGFß and IL-10 in the INFα group was not significantly different (P > 0.05). CONCLUSIONS: The results show that INFα-2b inhibits cancer cell immune evasion by decreasing the levels of CD4(+)CD25(+)Foxp3(+) Tregs and suppressing the expression of TGFß and IL-10 in the tumor microenvironment.

Expression of integrin-binding protein Nischarin in metastatic breast cancer.

The present study aimed to investigate the expression of Nischarin protein in primary breast cancer (PBC), and to evaluate its role in tumor metastasis. Paired specimens of breast cancer tissues and adjacent normal tissues were surgically obtained from 60 patients with PBC at the Zhejiang Cancer Hospital (Hangzhou, China). Nischarin protein concentrations were determined by an ELISA assay. Breast cancer tissues exhibited a significantly lower concentration of Nischarin (5.86 ± 3.19 ng/ml) compared with that of the adjacent noncancerous tissues (9.25 ± 3.65 ng/ml; P<0.001). Furthermore, cancer tissue from patients with lymph node metastasis had significantly lower levels of Nischarin protein (4.69 ± 2.40 ng/ml) than those of patients without lymph node metastasis (7.04 ± 3.47 ng/ml; P=0.004). There was no significant difference in Nischarin protein expression levels between patients with grade I, II or III PBC (grade I, 5.44 ± 3.57 ng/ml; grade II, 6.42 ± 3.85 ng/ml and grade III, 5.10 ± 1.18 ng/ml; P=0.765). The significant differences in the expression of Nischarin between: i) Cancer tissue and noncancerous tissue and ii) patients with and without lymph node metastasis, suggested that Nischarin may have a significant role in tumor occurrence and metastasis of breast cancer. Nischarin expression may therefore be used as a marker to predict the invasiveness and metastasis of PBC.

Serum tissue polypeptide-specific antigen is an independent predictor in breast cancer.

Tissue polypeptide-specific antigen (TPS) is a tumor proliferative marker associated with cytokeratin 18. The aim of the study was to investigate the potential relationship between the preoperative serum TPS levels and the outcome in Chinese breast cancer patients. 975 consecutive female patients, affected by invasive breast cancer under investigation from January 2005 to December 2011, had their TPS levels measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cut-off value was 80U/L. The average age diagnosed with breast cancer was 48, ranging from 23 to 71. About 19% (185) patients displayed an elevated preoperative TPS level (>80U/L) associated with older age (>45), advanced cancer stage, larger tumor size (>2cm), axillary lymph node metastasis, negative progesterone receptor status, and positive HER2 status. In addition, preoperative TPS levels were also significantly connected with recurrence (p<0.05), particularly distant metastasis and visceral metastasis. The mean preoperative TPS level was 68.4±116.43U/L (range 0-1839U/L). In multivariate analysis, high preoperative TPS level was recognized as an independent prognostic factor for disease-free survival (p<0.001 and overall survival (p=0.023). From these results we conclude that the serum preoperative TPS level may be a valuable and independent marker for breast cancer.

A support vector machine model for predicting non-sentinel lymph node status in patients with sentinel lymph node positive breast cancer.

This study aimed to investigate the accuracy and feasibility of support vector machine (SVM) modeling in predicting non-sentinel lymph node (NSLN) status in patients with SLN-positive breast cancer. Clinicopathological data were collected from 201 cases with sentinel lymph node biopsy breast cancer and included patient age, tumor size, histological type and grade, vascular invasion, estrogen receptor status, progesterone receptor status, CerbB2 status, size and number of positive SLNs, number of negative SLNs, and positive SLN membrane invasion. Feature vector selection was based on a combination of statistical filtration and model-dependent screening. The arbitrary combination with the smallest p value for SVM input was selected, the predicative results of the model were evaluated by a 10-fold cross validation, and a training model was established. Using SLN-positive patients as a double-blind test set, 85 patients were input into the model to analyze its sensitivity and specificity. The combination with the highest cross-validation accuracy was selected for the SVM model and consisted of the following: the number and size of positive SLNs, the number of negative SLNs, and the membrane invasion of positive SLNs. The training accuracy of the model established with the four variables was 92 %, and its cross-validation veracity was 87.6 %. The accuracy of an 85-patient double-blind test of the SVM model was 91.8 %. In conclusion, this SVM model is an accurate and feasible method for the prediction of NSLN status in SLN-positive breast cancer and is conducive to guide clinical treatment.