Indian Breast Cancer Patients Research Articles

Integrative multiomics analysis identifies a metastasis-related gene signature and the potential oncogenic role of EZR in breast cancer.

Distant metastasis is a major cause of increased mortality in breast cancer patients, but the mechanisms underlying breast cancer metastasis remain poorly understood. In this study, we aimed to identify a metastasis-related gene (MRG) signature for predicting progression in breast cancer. By screening using three regression analysis methods, a 9-gene signature (NOTCH1, PTP4A3, MMP13, MACC1, EZR, NEDD9, PIK3CA, F2RL1 and CCR7) was constructed based on an MRG set in the BRCA cohort from TCGA. This signature exhibited strong robustness, and its generalizability was verified in the Metabric and GEO cohorts. Of the nine MRGs, EZR is an oncogenic gene with a well-documented role in cell adhesion and cell migration, but it has rarely been investigated in breast cancer. Based on a search of different databases, EZR was found to be significantly more highly expressed in both breast cancer cells and breast cancer tissue. EZR knockdown significantly inhibited cell proliferation, invasion, chemoresistance and EMT in breast cancer. Mechanistically, RhoA activation assays confirmed that EZR knockdown inhibited the activity of RhoA, Rac1 and Cdc42. In summary, we identified a nine-MRG signature that can be used as an efficient prognostic indicator for breast cancer patients, and owing to its involvement in regulating breast cancer metastasis, EZR might serve as a therapeutic target.

Epigenetic Alteration and its Association With Downregulated FOXP3 Gene in Indian Breast Cancer Patients.

Background: FOXP3 gene, known to be a potential tumor suppressor, has been identified to interact with HER2 in mammary cancer. Moreover, the high expression of FOXP3 serves as a good predictor of the survival of patients in breast cancer, prostate cancer, and gastric cancer. The expression and epigenetic alterations were evaluated in female breast cancer patients. Material and Methods: Expression studies at the mRNA level and protein level were conducted in 140 breast cancer cases by real-time PCR and immunohistochemistry, respectively. Epigenetic studies were also conducted by analyzing the methylation status at the promoter region of the gene using MS-PCR. Results: FOXP3 mRNA expression and protein expression were downregulated in breast cancer patients. The absence of FOXP3 protein expression is significantly associated with promoter methylation, where 70 methylated cases exhibited protein loss (70/95, 73.6%). Statistically, we also found a significant correlation between FOXP3 protein expression and TNM stage, promoter methylation, and histological grade. The methylated FOXP3 cases that did not express protein were also significantly associated with positive lymph node metastasis and HER-2 status. Conclusion: The expression profile of FOXP3 may serve as a prognostic factor. In short, FOXP3 may stand in the most crucial list of biomarkers for breast cancer, bringing compelling results in terms of treatment and management of the disease.

Comparison of the Efficacy, Safety, Pharmacokinetic and Immunogenicity of UJVIRA (ZRC-3256, Trastuzumab Emtansine) With the Kadcyla (Trastuzumab Emtansine) in the Treatment of HER2-Positive Metastatic Breast Cancer: A Randomized, Open-Label, Multicenter Study in India

BackgroundUJVIRA is the first DCGI approved biosimilar of trastuzumab emtansine (Kadcyla) which may offer an alternative cost-effective treatment option for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients in India. This article summarizes the available clinical evidence supporting the biosimilarity of UJVIRA and Kadcyla with respect to efficacy, pharmacokinetic, safety, and immunogenicity. Materials and methodsA phase 3, randomized, open-label, active-controlled study was conducted at 31 sites across India. A total of 168 patients were enrolled and randomized to receive either UJVIRA or Kadcyla. Of which, only first 50 patients were included in pharmacokinetic assessment. UJVIRA or Kadcyla were administered at a dose of 3.6 mg/kg by intravenous infusion every 3 weeks (21 days) for 8 cycles or until disease progression or unmanageable toxicity, whichever was earlier. The study assessed efficacy (ORR), safety, pharmacokinetics, and immunogenicity. ResultsThe ORR at the end of Week 24 was 37.76% in the UJVIRA and 33.33% in the Kadcyla group. The risk difference was 4.42% [-12.01, 20.85]. It met noninferiority margin of -15%. The pharmacokinetic parameters were comparable between groups. No antidrug antibody was detected in any of the treatment groups. The overall safety profile in terms of TEAEs and laboratory abnormalities was also comparable between the treatment groups. ConclusionResults demonstrated biosimilarity between UJVIRA and Kadcyla in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Therefore, UJVIRA could prove to be a cost-effective treatment alternative for HER2-positive metastatic breast cancer patients in India.

Trends in Axillary Management of Early Breast Cancer: a Questionnaire-Based Pattern of Practice Survey for India.

Surgical management of breast cancer (BC) has evolved from radical surgeries to conservative with better cosmetic and comparable oncological outcomes. For axillary staging, it has evolved from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB). No detailed information exists in terms of the clinical practice pattern of surgical management of axilla for BC patients in India. A questionnaire-based survey was developed. The survey was done at the annual meeting of the Association of Breast Surgeons of India (ABSI) in November 2018. Responses were recorded and analysed by SPSS 23. One hundred twelve out of 400 (28%) responded to the survey. Half of the respondents were surgical oncologist and 36.6% were performing > 150BC surgeries/year. The primary technique for axillary staging in node-negative BC was SLNB for 68.5% of respondents. Majority of surgeons (47%) reported performing SLNB by methylene blue dye only. Unavailability of radioisotope (46.7%) and lack of frozen section (26.7%) were reported as two major barriers for not performing SLNB. Twenty-three percent did perform SLNB in post-NACT setting. Only 15.8% have omitted completion ALND in Z0011 trial eligible SLN-positive patients. 45.9% skipped completion ALND in SLN positive with micro metastasis only. Many surgeons in India are adopting SLNB as a method of axillary staging into their clinical practice. However, large number of surgeons still believe in conservative approach, most probably due to unavailability of resources and lack of Indian data. Barrier identified in this survey may be useful for future development.

Evaluation of Rare Types of Breast Cancer among Indian Patients - a Retrospective Study from a Regional Cancer Center.

Breast cancer (BC) is the most common cancer among Indian women and invasive duct cell carcinoma (IDCC) the most common histology (80-90%) followed by noninvasive duct cell carcinoma (non-IDCC) subtypes (about 10%). Most of the non-IDCC are rare (<1-2%), and literature on this topic is sparse. Age is an important prognostic factor and varies with ethnicity. The aim of our study is to evaluate the incidence and age at presentation of different types of BC. This is a single institute retrospective observational study evaluating BC over the last 7 years at our institute. We evaluated the demographic and pathological features. There were a total of 2725 patients, of these 89.7% had IDCC and 10.2% had non-IDCC. There were 13 subtypes of non-IDCC, the most common being sarcoma/phyllodes (2.4%) and lobular (2.3%). The other subtypes were very rare (<1.5% each). The non-IDCC male BC was very rare (0.07%). The median age at presentation was similar for IDCC and non-IDCC types (50years). The p value for age at presentation was significant for mucinous (0.0001), phyllodes (<0.0001), and sarcoma breast (0.009) when compared with IDCC. The incidence of IDCC, non-IDCC, and rare subtypes of non-IDCC are comparable to literature except lobular (lower) and phyllodes/sarcoma (higher). Indian patients presented a decade earlier for both IDCC and non-IDCC types. Tubular and papillary presented at an age comparable to IDCC, in contrast to the West. Given these differences, the prognosis of non-IDCC needs to be evaluated in future studies on Indian BC patients.

Prognostic Nutritional Index (PNI) in Patients With Breast Cancer Treated With Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

ObjectivePrognostic nutritional index (PNI), calculated as serum albumin (ALB) (g/L) + 5 × total lymphocyte count (109/L), is initially used to evaluate nutritional status in patients undergoing surgery and may evaluate the therapeutic effects and predict the survival of various solid tumors. The present study aimed to evaluate the potential prognostic significance of PNI in breast cancer patients receiving neoadjuvant chemotherapy (NACT).MethodsA total of 785 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of PNI by receiver operating characteristic curve stratified patients into a low-PNI group (<51) and a high PNI group (≥51). The associations between breast cancer and clinicopathological variables by PNI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC).ResultsThe results indicated that PNI had prognostic significance by an optimal cutoff value of 51 on DFS and OS in univariate and multivariate Cox regression survival analyses. Breast cancer patients with a high PNI value had longer DFS and OS than those with a low PNI value [47.64 vs. 36.60 months, P < 0.0001, hazard ratio (HR) = 0.264, 95%CI = 0.160–0.435; 73.61 vs. 64.97 months, P < 0.0001, HR = 0.319, 95%CI = 0.207–0.491, respectively]. Furthermore, the results indicated that patients with high PNI had longer DFS and OS than those with low PNI in early stage and advanced breast cancer, especially in advanced breast cancer. The mean DFS and OS times for breast cancer patients with high PNI by the log-rank test were longer than in those with low PNI in different molecular subtypes. Moreover, the mean DFS and OS times in patients with high PNI by the log-rank test were longer than in those patients with low PNI without or with lymph vessel invasion. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the PNI had no significance on the toxicities of all enrolled patients, except in anemia, leukopenia, and myelosuppression.ConclusionPretreatment PNI with the advantages of being convenient, noninvasive, and reproducible was a useful prognostic indicator for breast cancer patients receiving neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Impact of RASSF1A gene methylation on clinico-pathological features of tumor and non-tumor tissue of breast cancer

BackgroundBreast cancer is the most common malignancy in women caused by genetic and epigenetic changes. Promoter DNA methylation in tumor suppressor gene plays a major role in breast cancer. The study determined the association of promoter DNA methylation of RASSF1A gene with clinicopathological features in tumor and non-tumor tissue. Materials and methodsA cross sectional study was conducted in the Department of Pathology, Government Institute of Medical Sciences, Greater Noida and Molecular Pathology Laboratory, Department of Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences. Two sections, one from tumor and the other from non-tumor tissue, were obtained and processed for DNA extraction and bisulphite conversion. Methylation specific PCR was done and results of RASSF1A promoter methylation were statistically correlated with clinicopathological features. ResultsOf the 27 breast cancer tissue, 22 showed invasive ductal carcinoma, one showed invasive lobular carcinoma, another showed ductal carcinoma in situ and three cases showed malignant phyllodes tumor of breast. DNA promoter methylation was found in all the cases. 93% of tumor tissue samples and 67% of the non-tumor tissue samples were found to be aberrantly methylated. Tumor size and histological grade were found to be significantly (p-val <0.05) associated with the RASSF1A gene promoter methylation. ConclusionA significant association of higher tumor size and tumor histological grade with promoter methylation of RASSF1A gene exists suggestive of its being an important determinant of prognostic staging. This critical event in tumorigenesis may be of clinical utility in assessing breast cancer progression. Micro abstractThe study focuses on the RASSF1A gene promoter methylation and its impact on the clinicopathological features in Indian breast cancer patients highlighting the differences from other genetically different population. We found that RASFF1A gene methylation has significant impact on tumor size and tumor grade. The work carries high significance because it addresses the DNA methylation of tumor suppressor gene in relevance of breast cancer. It may also be the first such report on Indian patients with breast cancer.

Combining bioinformatics analysis and experiments to explore CARNS1 as a prognostic biomarker for breast cancer.

BackgroundBreast cancer is a heterogeneous malignant disease, which has variation in clinical behaviors. High‐throughput technologies have added important genetic alternative and biological change information for breast cancer. CARNS1 is an important ATPases. It can catalyze the synthesis of carnosine, which has antiproliferative activity in cancer. Here, we hypothesize that CARNS1 plays an essential role in the development of breast cancer.MethodsThe expressions of CARNS1 in breast cancer were data‐mined and analyzed from TCGA (the Cancer Genome Atlas) and GEO (the Gene Expression Omnibus) databases. The correlation of CARNS1 expression with clinical characteristics and the diagnostic capability of CARNS1 were assessed. Experimental studies were conducted in two cohorts (n = 60) of breast cancer patients by qRT‐PCR and immunohistochemical analysis.Results CARNS1 was significantly downregulated in breast cancer. The expression was correlated with tumor molecular and histological types, T and M stages, and vital status. Kaplan–Meier survival analysis showed that the downregulation of CARNS1 was significantly related to poor overall survival and relapse‐free survival. Moreover, these scenarios have been extended to ER, PR, and HER2 positive patients. Univariate and multivariate analysis showed that CARNS1 can be considered as an independent prognostic predictor for patients with breast cancer. Experimental data supported that the protein and mRNA levels of CARNS1 in breast cancer are indeed significantly downregulated.ConclusionOur findings have demonstrated that CARNS1 acts as a tumor suppressor gene and may be an independent prognostic indicator for breast cancer patients.

An Overview of Genes Associated with Hereditary Breast and Ovarian Cancer in India

Cancer is a dreadful disease, with genetics being a significant causative etiological factor. About 5–10% of the cancers arise through the congenital alteration of a group of genes which are predisposition genetic factor. Inherited mutation can play a role in leading or receding fashion that can deliberate varied degree of penetrance. The risk for causing hereditary cancer mainly focused on identification of BRCA1 and BRCA2, which are high-penetrance breast cancer genes linked with the highest lifetime cancer risks. The hereditary breast and ovarian cancer is also attributed to alterations in various other breast and ovarian cancer susceptibility genes. In this review, a comprehensive information of genes associated with HBOC is discussed. Extensive data are gathered using different search tools for Indian studies related to HBOC. It revealed that genetic prevalence of hereditary breast and ovarian cancer in Indian population is less explored. There are very few large-scale studies in Indian population related to HBOC. Further, there is lack of studies that analyzed various other high-penetrance gene except BRCA1/BRCA2 in Indian HBOC patients. There are various limiting factors like ethnicity, clinical history for inclusion and exclusion, inconsistency in method used for analysis, etc. The study suggested that a strategic approach is required for Indian hereditary breast and ovarian cancer patients.

Ten-year survival outcome of breast cancer patients in India.

INTRODUCTION:Breast cancer is the most frequently diagnosed cancer among women in India; however, there are no studies addressing long-term survival (10 years and above). This study sought to evaluate long-term oncological outcome among women with breast cancer treated with a curative intent.MATERIALS AND METHODS:This is a retrospective cohort analysis of 1301 breast cancer patients of all stages who had received primary treatment with curative intent from 2004 to 2010 at a single cancer institution of India.RESULTS:A total of 1301 breast cancer patients were available for final analysis. The median age was 51 years (range, 21–86 years). 70.25% of the patients had early breast cancer (EBC), 21.9% had locally advanced breast cancer, and 7.85% of the patients with de novo metastatic disease also underwent surgery. 56.5% of the patients had hormone-sensitive tumors, human epidermal growth factor receptor 2 over expression was seen in 17%, and triple-negative tumors accounted for 26.2% of the patients. The 5- and 10-year overall survival (OS) of the entire cohort was 79% and 66%, and the 5- and 10-year breast cancer-specific survival (BCSS) was 79% and 70%, respectively. OS and BCSS were 51% and 58%, respectively, at 15-year follow-up after primary cancer treatment. On multivariate analysis, the factors associated with prolonged survival were age ≤50 years, EBC, and treatment during the later period (2008–2010).CONCLUSION:Difference between OS and BCSS was found to have an increasing trend during 10–15-year follow-up, the difference being 4% at 10 years and 7% at 15 years. Age ≤50 years, early-stage disease at presentation, and primary cancer treatment in later years (2008–2010) were favorable predictors for 10-year survival.

Prevalence of Epstein–Barr virus in North-East Indian breast cancer patients' blood

Prevalence of Epstein–Barr virus in North-East Indian breast cancer patients' blood

Breast Cancer Detection Using Supervised Machine Learning Algorithm

The most commonly causing cancer among Indian women is breast cancer and it effecting all over world with its impact. According to the medical reports of breast cancer patients in India were unable to hold the pain and about half of them are dying. In the proposed work used a machine learning algorithm to decrease the pre-processing time and to detection the symptoms and for better accuracy. The system is trained pre-processed image of fed to the system which are in the form of mammograms in common the X-ray of breast. The system which has the data segregated into the training and testing datasets analyses the input images based on the characters or the labels assigned to them done with the application of few of the algorithms which are present in the machine learning we compare the data or the image and probable output based on the character labels is obtained in the form of result. Compared to existing work and the proposed machine learning model as a serious of combination and permutations of algorithms lead to increase in the efficacy of the result and got the accuracy of 97.4% using random forests algorithm.

Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients

BackgroundTelomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues.ResultsPatients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS.ConclusionAssessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

A Multicentre Observational Study on Risk Factors for Breast Cancer.

Breast cancer is the most common malignancy in Indian women. There is scant data from Indian hospital-based populations on the prevalence of risk factors of this disease. We performed this study to quantify and analyze various epidemiological risk factors in Indian breast cancer patients. This was a multicenter collaborative study wherein breast cancer patients older than 18years were served a structured questionnaire after informed consent. Patients or their relatives were required to fill out the questionnaire and those who were unable to read and write were excluded. Data were abstracted from case record forms and variables were descriptively analyzed. Between January 2015 and February 2016, 800 patients were screened, of whom 736 patientswith a mean age of 50.13years were enrolled in the study. The mean number of pregnancies was 2.75 (0-11), the number (percentage) of women who had breastfed for more than 6months was 628 (85.3) and 406 (55.1%) patients were post-menopausal at the time of breast cancer diagnosis. Of the enrolled patients, 91 (12.8%) had history of exposure to passive smoke, 13 (1.8%) had partners who were heavy smokers, 27(3.7%) had history of oral contraceptive use, 4 (0.5%) had history of hormone replacement therapy, and 103 (14%) had undergone hysterectomy with oophorectomy. Our study contributes to the descriptive prevalence of some known risk factors in Indian breast cancer patients.

Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.

Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab. Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis. Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0months; high group 54.0months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028). We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.

Pretreatment Systemic Inflammation Response Index in Patients with Breast Cancer Treated with Neoadjuvant Chemotherapy as a Useful Prognostic Indicator.

Background and ObjectiveSystemic inflammation response index (SIRI=N×M/L), based on neutrophil (N), monocyte (M), and lymphocyte (L) counts, is used to predict the survival of patients with malignant tumors and can fully evaluate the balance between host immune and inflammatory condition. The present study is aimed to evaluate the potential prognostic significance of SIRI in patients with breast cancer undergoing neoadjuvant chemotherapy.Subjects and MethodsA total of 262 breast cancer patients treated with neoadjuvant chemotherapy were enrolled in this retrospective study. The optimal cutoff value of SIRI by receiver operating characteristic curve stratified patients into low SIRI (<0.85×109/L) group and high SIRI (≥0.85×109/L) group. The associations between breast cancer and clinicopathological variables by SIRI were determined by chi-square test or Fisher’s exact test. Kaplan–Meier plots and log-rank test were used to evaluate the clinical outcomes of disease-free survival (DFS) and overall survival (OS). Univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of SIRI. The toxicity of neoadjuvant chemotherapy was evaluated by the National Cancer Institute Common Toxicity Criteria (NCICTC).ResultsThe results were shown that SIRI had prognostic significance by optimal cutoff value of 0.85×109/L on DFS and OS in univariate and multivariate Cox regression survival analyses. Compared with patients who had high SIRI, patients with low SIRI had longer DFS and OS (41.27 vs 30.45 months, HR: 1.694, 95% CI: 1.128–2.543, P=0.011; 52.86 vs 45.75 months, HR: 1.288, 95% CI: 0.781–3.124, P=0.002, respectively). The patients with low SIRI had better 3-, 5-, and 10-year rates of DFS and OS than those with high SIRI. The common toxicities after neoadjuvant chemotherapy were hematologic and gastrointestinal reaction, and the SIRI had no significance on toxicities of all enrolled patients, excepted diarrhea. In patients without neural invasion, those with low SIRI had better prognosis and lower recurrence rates than those with high SIRI.ConclusionPretreatment SIRI with the advantage of repeatable, convenient, and non-invasive is a useful prognostic indicator for breast cancer patients who received neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Pre-treatment systemic immune-inflammation index is a useful prognostic indicator in patients with breast cancer undergoing neoadjuvant chemotherapy.

The systemic immune‐inflammation index (SII = N × P/L) based on neutrophil (N), platelet (P) and lymphocyte (L) counts is used to predict the survival of patients with malignant tumours and can fully reflect the balance between host inflammatory and immune status. This study is conducted to explore the potential prognostic significance of SII in patients with breast cancer undergoing neoadjuvant chemotherapy (NACT). A total of 262 patients with breast cancer received NACT were enrolled in this study. According to the receiver operating characteristic curve, the optimal cut‐off value of SII was divided into two groups: low SII group (<602 × 109/L) and high SII group (≥602 × 109/L). The associations between breast cancer and clinicopathological variables by SII were determined by chi‐squared test or Fisher's exact test. The Kaplan‐Meier plots and log‐rank test were used to determine clinical outcomes of disease‐free survival (DFS) and overall survival (OS). The prognostic value of SII was analysed by univariate and multivariate Cox proportional hazards regression models. The toxicity of NACT was accessed by National Cancer Institute Common Toxicity Criteria (NCICTC). According to univariate and multivariate Cox regression survival analyses, the results showed that the value of SII had prognostic significance for DFS and OS. The patients with low SII value had longer DFS and OS than those with high SII value (31.11 vs 40.76 months, HR: 1.075, 95% CI: 0.718‐1.610, P = .006; 44.47 vs 53.68 months, HR: 1.051, 95% CI: 0.707‐1.564, P = .005, respectively). The incidence of DFS and OS in breast cancer patients with low SII value was higher than that in those patients with high SII value in 3‐, 5‐ and 10‐year rates. The common toxicities after NACT were haematological and gastrointestinal reaction, and there were no differences by SII for the assessment of side effects of neoadjuvant chemotherapy. Meanwhile, the results also proved that breast cancer patients with low SII value and high Miller and Payne grade (MPG) survived longer than those breast cancer with high SII value and low MPG grade. In patients without lymph vessel invasion, these breast cancer patients with low SII value had better prognosis and lower recurrence rates than those with high SII value. Pre‐treatment SII with the advantage of reproducible, convenient and non‐invasive was a useful prognostic indicator for breast cancer patients undergoing neoadjuvant chemotherapy and is a promising biomarker for breast cancer on treatment strategy decisions.

Breast Anthropometry-Results of a Prospective Study Among Indian Breast Cancer Patients.

Breast anthropometry plays an important role in surgical decision-making in the era of breast conservation therapy, oncoplasty and reconstruction. Majority of the currently available breast anthropometry data is from Western countries, and there is a need to evaluate anthropometric data among Indian women to tailor our surgical decision-making and achieve optimum surgical results. Two hundred and thirty-one breast cancer patients were included in this prospective study, and different anthropometric parameters were evaluated to assess and describe the nipple-areola complex, breast shape, size, volume and ptosis. Breast volume was calculated using formula developed by Qiao et al. Outcomes were compared with data available from different countries. Mean breast volume among Indian women was 515ml. Nearly, 81% of patients had ptosis and up to 40% had grade 3 ptosis. Breast volume among Indian patients can be grouped into three categories based on quartiles (category I-≤ 220ml, category II-> 220 to ≤ 730ml, category III-> 730ml). Overall breast anthropometry data among Indian women was different from the data reported from western studies. Breast anthropometry plays an important role in the surgical decision-making, and results of the study indicate that the anthropometry of Indian women is different from western counterparts.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells.

ObjectiveAlthough T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated.MethodsTim-3 gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells. ResultsIn a pooled analysis of The Cancer Genome Atlas (TCGA) database, Tim-3 gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3low breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (CCND1), C-Myc, matrix metalloproteinase-1(MMP1), TWIST, vascular endothelial growth factor (VEGF) upregulation, concomitant with E-cadherin downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression. ConclusionsTim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

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.