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Breast cancer - Top 30 Publications

Using the Modified Magee Equation to Identify Patients Unlikely to Benefit From the 21-Gene Recurrence Score Assay (Oncotype DX Assay).

This study aimed to compare a modified Magee equation with Oncotype DX (Genomic Health, Redwood City, CA) recurrence score (RS) and identify patients who are unlikely to benefit from Oncotype DX.

Dual responsive magnetic composite nanogels for thermo-chemotherapy.

With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204W/g for the concentration of 2mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.

New agents for endocrine resistance in breast cancer.

Estrogen receptor positive (ER+) and HER2-negative (HER2-) breast cancer (BC) is the most common BC subtype, defined by expression of the ER and absence of HER2 amplification. Endocrine treatment (ET), aiming at therapeutic blockade of ER signaling, represents the therapeutic mainstay for patients with both early and advanced disease. Despite its wide therapeutic efficacy, ET fails for a proportion of ER+, HER2- BC patients with early disease who develop endocrine resistance, resulting in disease recurrence. Endocrine resistance occurs almost invariably in patients with metastatic disease. Recently, increasing understanding of the molecular mediators of endocrine resistance has been achieved. This review focuses on the molecular mechanisms mediating endocrine resistance, on molecularly targeted agents to overcome or delay it, and potential predictive biomarkers for accurate patient stratification.

Breast cancer detection in automated 3D breast ultrasound using iso-contours and cascaded RUSBoosts.

Automated 3D breast ultrasound (ABUS) is a new popular modality as an adjunct to mammography for detecting cancers in women with dense breasts. In this paper, a multi-stage computer aided detection system is proposed to detect cancers in ABUS images. In the first step, an efficient despeckling method called OBNLM is applied on the images to reduce speckle noise. Afterwards, a new algorithm based on isocontours is applied to detect initial candidates as the boundary of masses is hypo echoic. To reduce false generated isocontours, features such as hypoechoicity, roundness, area and contour strength are used. Consequently, the resulted candidates are further processed by a cascade classifier whose base classifiers are Random Under-Sampling Boosting (RUSBoost) that are introduced to deal with imbalanced datasets. Each base classifier is trained on a group of features like Gabor, LBP, GLCM and other features. Performance of the proposed system was evaluated using 104 volumes from 74 patients, including 112 malignant lesions. According to Free Response Operating Characteristic (FROC) analysis, the proposed system achieved the region-based sensitivity and case-based sensitivity of 68% and 76% at one false positive per image.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes.

Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women.

Complementary and alternative medicine (CAM) use and delays in presentation and diagnosis of breast cancer patients in public hospitals in Malaysia.

Complementary and alternative medicine (CAM) is widely used among the breast cancer patients in Malaysia. Delays in presentation, diagnosis and treatment have been shown to impact the disease prognosis. There is considerable use of CAM amongst breast cancer patients. CAM use has been cited as a cause of delay in diagnosis and treatments in qualitative studies, however there had not been any confirmatory study that confirms its impact on delays. The purpose of this study was to evaluate whether the use of CAM among newly diagnosed breast cancer patients was associated with delays in presentation, diagnosis or treatment of breast cancer. This multi-centre cross-sectional study evaluating the time points of the individual breast cancer patients' journey from first visit, resolution of diagnosis and treatments was conducted in six public hospitals in Malaysia. All newly diagnosed breast cancer patients from 1st January to 31st December 2012 were recruited. Data were collected through medical records review and patient interview by using a structured questionnaire. Complementary and alternative medicine (CAM) was defined as the use of any methods and products not included in conventional allopathic medicine before commencement of treatments. Presentation delay was defined as time taken from symptom discovery to first presentation of more than 3 months. The time points were categorised to diagnosis delay was defined as time taken from first presentation to diagnosis of more than 1 month and treatment delay was defined as time taken from diagnosis to initial treatment of more than 1 month. Multiple logistic regression was used for analysis. A total number of 340 patients participated in this study. The prevalence of CAM use was 46.5% (n = 158). Malay ethnicity (OR 3.32; 95% CI: 1.85, 5.97) and not interpreting symptom as cancerous (OR 1.79; 95% CI: 1.10, 2.92) were significantly associated with CAM use. The use of CAM was associated with delays in presentation (OR 1.65; 95% CI: 1.05, 2.59), diagnosis (OR 2.42; 95% CI: 1.56, 3.77) and treatment of breast cancer (OR 1.74; 95% CI: 1.11, 2.72) on univariate analyses. However, after adjusting with other covariates, CAM use was associated with delays in presentation (OR 1.71; 95% CI: 1.05, 2.78) and diagnosis (OR 2.58; 95% CI: 1.59, 4.17) but not for treatment of breast cancer (OR 1.58; 95% CI: 0.98, 2.55). The prevalence of CAM use among the breast cancer patients was high. Women of Malay ethnicity and not interpreting symptom as cancerous were significantly associated with CAM use. The use of CAM is significantly associated with delay in presentation and resolution of diagnosis. This study suggests further evaluation of access to breast cancer care is needed as poor access may cause the use of CAM. However, since public hospitals in Malaysia are heavily subsidized and readily available to the population, CAM use may impact delays in presentation and diagnosis.

Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the proliferation of MCF-7 breast cancer cells.

In recent years, by extensive achievements in understanding the mechanisms and the pathways affected by cancer, the focus of cancer research is shifting from developing new chemotherapy methods to using natural compounds with therapeutic properties to reduce the adverse effects of synthetic drugs on human health. We used fruit extracts from previously generated human type I InsP 5-ptase gene expressing transgenic tomato plants for assessment of the anti-cancer activity of established genetically modified tomato lines. Cellular assays (MTT, Fluorescent microscopy, Flow Cytometry analysis) were used to confirm that InsP 5-ptase fruit extract was more effective for reducing the proliferation of breast cancer cells compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase expressing tomato fruits performed by LC-MS identified tomato metabolites that may play a key role in the increased anti-cancer activity observed for the transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line) exposed to an extract of transgenic fruits revealed a number of differently regulated genes in the cells treated with transgenic extract compared to untreated cells or cells treated with wild-type tomato extract. Together, this data demonstrate the potential role of the plant derived metabolites in suppressing cell viability of cancer cells and further prove the potential application of plant genetic engineering in the cancer research and drug discovery.

Long-term Results After Oncoplastic Surgery for Breast Cancer: A 10-year Follow-up.

The aim of this study was to evaluate the long-term oncologic outcome after oncoplastic surgery (OPS).

Circulating cell-free microRNAs as clinical cancer biomarkers.

MicroRNAs (miRNAs) are non-coding small RNAs that are master regulators of genic expression and consequently of many cellular processes. But their expression is often deregulated in human tumors leading to cancer development. Recently miRNAs were discovered in body fluids (serum, plasma and others) and their levels have often been reported to be altered in patients. Circulating miRNAs became one of the most promising biomarkers in oncology for early diagnosis, prognosis and therapeutic response prediction. Here we describe the origins and roles of miRNAs, and summarize the most recent studies focusing on their usefulness as cancer biomarkers in lung, breast, colon, prostate, ovary cancers and melanoma. Lastly, we describe the main methodologies related to miRNA detection, which should be standardized for their use in clinical practice.

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10(-6)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10(-9)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Antitumor activity of fucoidan in anaplastic thyroid cancer via apoptosis and anti-angiogenesis.

The present study demonstrated the effect of fucoidan, isolated from Fucus vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The cell viability was analyzed using a Cell Counting Kit‑8 cell proliferation kit. Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP nick‑end labeling assays were used to examine the apoptotic effect of fucoidan, which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan inhibited the growth of FTC133 and TPC1 ATC cells in a dose‑dependent manner. It also induced the apoptosis of FTC133 cells by promoting the expression levels of cleaved poly ADP‑ribose polymerase and caspase‑3. Significant decreases in the levels expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were observed in the FTC133 cells following treatment of the cells with fucoidan. In addition, inhibition in tube formation and the migration of FTC133 cells were observed in the cells treated with fucoidan, compared with the cells in the control group. Therefore, fucoidan inhibited cell growth, induced apoptosis and suppressed angiogenesis in the thyroid cancer cells.

Binding of circulating anti-MUC1 antibody and serum MUC1 antigen in stage IV breast cancer.

The present study aimed to investigate the binding of circulating mucin 1 (MUC1) antibody with serum MUC1 antigen in stage IV breast cancer. Serum samples of 61 patients with stage IV breast cancer and 64 patients with early-stage breast cancer were collected. The anti‑MUC1 antibody (IgG) and MUC1 antigen (cancer antigen 15‑3; Ca15‑3) were detected using an indirect enzyme-linked immunosorbent assay (I‑ELISA) and ELISA, respectively. The MUC1 IgG affinity was detected using a urea degradation combining ELISA. Western blot analysis and an inhibition test were performed for verification of the binding of anti‑MUC1 IgG with MUC1 antigen, and their correlation was analyzed. The results showed that there was a negative correlation between anti‑MUC1 IgG and CA15‑3 antigen in stage IV breast cancer when positive CA15‑3 antigen and/or anti‑MUC1 IgG were selected (r=‑0.417; P=0.0044). The positive anti‑MUC1 IgG with positive Ca15‑3 antigen was more common in stage IV breast cancer, compared with early‑stage breast cancer (χ2=4.629; P=0.031), however, Ca15‑3 antigen positivity was higher in stage IV breast cancer, compared with early‑stage breast cancer (χ2=10.58; P=0.001). Anti‑MUC1 IgG was able to bind to the MUC1 antigen in stage IV breast cancer. No differences in the 8R-MUCPT inhibition ratio were found between the two groups (P=0.778), and there were no differences in the affinity of anti‑MUC1 IgG (P=0.873). In stage IV breast cancer, circulating anti‑MUC1 antibody was found to bind serum MUC1 antigen, although their compatibility was low. No significant difference was found in the affinity of the anti‑MUC1 antibody between stage IV breast cancer and early‑stage breast cancer.

Pain, sensory disturbances and psychological distress are common sequelae after treatment of ductal carcinoma in situ: a cross-sectional study.

Sequelae such as pain, sensory disturbances and psychological distress are well known after treatment for invasive breast cancer (IBC). Patients treated for ductal carcinoma in situ (DCIS) receive a similar treatment as low-risk IBC. The aim of this cross-sectional study was to describe prevalence of postoperative pain, sensory disturbances, psychological distress and rehabilitation needs among Danish women with DCIS.

The influence of different muscle mass measurements on the diagnosis of cancer cachexia.

Progressive loss of muscle mass is a major characteristic of cancer cachexia. Consensus definitions for cachexia provide different options to measure muscle mass. This study describes the effect of different methods to determine muscle mass on the diagnosis of cancer cachexia. In addition, the association of cachexia with other features of cachexia, quality of life, and survival was explored.

Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA.

Abbreviated breast dynamic contrast-enhanced MR imaging for lesion detection and characterization: the experience of an Italian oncologic center.

To evaluate the performance of an abbreviated dynamic contrast-enhanced MR imaging (MRI) protocol for breast cancer detection; a comparison with the complete diagnostic protocol has been conducted.

Relationship between IHC4 score and response to neo-adjuvant chemotherapy in estrogen receptor-positive breast cancer.

To determine whether IHC4 score assessed on pre-treatment core biopsies (i) predicts response to neo-adjuvant chemotherapy in ER-positive (ER+) breast cancer; (ii) provides more predictive information than Ki67 alone.

The potential role of three-dimensional surface imaging as a tool to evaluate aesthetic outcome after Breast Conserving Therapy (BCT).

To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT).

Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients.

Hepatitis C virus (HCV) is one of the major pathogens of chronic viral hepatitis, and approximately 38 million patients are infected with HCV in China. However, little information is available on the effect of HCV infection during chemotherapy for breast cancer and the impact of HCV infection on the toxicity of chemotherapy and targeted therapy.

Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32.

Metformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples.

Pertuzumab/Trastuzumab/CT Versus Trastuzumab/CT Therapy for HER2+ Breast Cancer: Results from the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).

Pertuzumab became a standard part of neoadjuvant therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancers approximately halfway through Neoadjuvant Breast Registry Symphony Trial (NBRST) enrollment, providing a unique opportunity to determine biologically which clinical HER2+ patients benefit most from dual targeting. As a neoadjuvant phase 4 study, NBRST classifies patients by both conventional and molecular subtyping.

Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese.

Whether age and inter-individual variability of pharmacogenetics are risk factors for paclitaxel-induced peripheral neuropathy (PIPN) is inconclusive. This study was conducted to evaluate the influence of previously investigated single nucleotide polymorphisms (SNPs) and age, using genotype data from a prospective study of paclitaxel-related toxicity in Japanese patients with breast cancer.

Co(II) Complexes of4-((3-ethoxy-2-hydroxybenzylidene)amino)-N-(thiazol-2-yl)benzenesulphonamide and 4-((pyridin-2-ylmethylene)amino)-N-(thiazol-2-tl)benzenesulfonamide: Synthesis, Fluorescence Properties and Anticancer Activity.

Two new Co(II) complexes of 4-((3-ethoxy-2-hydroxybenzylidene)amino)-N-(thiazol-2-yl)benzenesulphonamide and 4-((pyridin-2-ylmethylene)amino)-N-(thiazol-2-yl)benzene sulfonamide were synthesised. The structure of the complexes was identified by elemental analysis, FT-IR, electronic, EI mass, Powder XRD spectra and magnetic moment. The TG and DTA patterns of the complexes were supported the structures. The fluorescence quenching of these complexes with alizarin dye were premeditated and the free energy change (∆Get) for electron transfer process was designed by Rehm-Weller equation. The [Co(L1-H)2(H2O)2] and [Co(L2)2(H2O)2].2H2O were submitted for in vitro cytotoxicity studies in human breast cancer cell line (MCF 7).

Imaging diagnostics of breast metastases from extramammary tumors.

Breast metastases of solid extramammary tumors are very rare in comparison to primary malignancies of the breast and account for only 0.33-6.3% of all malignant neoplasms of the breast. The most common primary tumors are malignant melanoma, distant sarcomas, lung cancer, ovarian cancer, renal cell cancer and thyroid cancer in decreasing order of frequency. This review article summarizes the clinical features and the different imaging findings of breast metastases from different extramammary solid tumors. Breast metastases are often incidental findings in computed tomography (CT) or positron emission tomography CT (PET-CT) imaging. Mammography shows two different imaging patterns, namely focal lesions and diffuse architectural distortion with skin thickening. Breast metastases presenting as focal masses usually occur as solitary and more rarely as multiple round lesions with a smooth edge boundary. Associated calcifications are rare findings. Diffuse architectural distortion with skin thickening is more common in breast metastases from most gastric tumors, ovarian cancer and rhabdomyosarcoma. Using ultrasound most lesions are hypoechoic, oval or round with smooth boundaries and posterior acoustic enhancement. The magnetic resonance imaging (MRI) criteria of breast metastases show an inconstant signal behavior that cannot be safely classified as benign or malignant. In summary, in patients with known malignancies the presence of breast metastases should be considered even with imposing clinically and radiologically benign findings.

Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis.

Are Mast Cells MASTers in Cancer?

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of cancer. Mast cells form a heterogeneous population of immune cells with differences in their ultra-structure, morphology, mediator content, and surface receptors. Mast cells are widely distributed throughout all tissues and are stromal components of the inflammatory microenvironment that modulates tumor initiation and development. Although canonically associated with allergic disorders, mast cells are a major source of pro-tumorigenic (e.g., angiogenic and lymphangiogenic factors) and antitumorigenic molecules (e.g., TNF-α and IL-9), depending on the milieu. In certain neoplasias (e.g., gastric, thyroid and Hodgkin's lymphoma) mast cells play a pro-tumorigenic role, in others (e.g., breast cancer) a protective role, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of mast cells and their mediators could be cancer specific. The microlocalization (e.g., peritumoral vs intratumoral) of mast cells is another important aspect in the initiation/progression of solid and hematologic tumors. Increasing evidence in certain experimental models indicates that targeting mast cells and/or their mediators represent a potential therapeutic target in cancer. Thus, mast cells deserve focused consideration also as therapeutic targets in different types of tumors. There are many unanswered questions that should be addressed before we understand whether mast cells are an ally, adversary, or innocent bystanders in human cancers.

Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer.

Vasculogenic mimicry (VM), a newly defined pattern of tumor blood perfusion, describes the functional plasticity of aggressive tumor cells forming de novo vascular networks and is associated with the cancer progression and metastasis. However, the VM-positive rate and the impact of VM status on breast cancer patients' clinicopathological parameters and prognosis remain unclear. Thus, we performed a meta-analysis by incorporating all available evidence to clarify these issues. Eight studies that involved 1,238 breast cancer patients were eligible for inclusion in our study. We found the VM-positive rate was 24% (pooled proportion was 0.24, 95% CI= 0.13-0.34), and VM was significantly associated with larger tumor size (>2 cm) (OR=0.49, 95% CI=0.26-0.90, P=0.02) and lymph node metastasis (OR=0.27, 95% CI=0.13-0.57, P=0.0005). A boardline correlation was also identified between VM and poorer differentiation (Grade II-III) (OR=0.07, 95% CI=0.00-1.24, P=0.07). Nevertheless, no statistically significant associations were observed between VM and hormone receptor and human epidermal growth factor receptor 2 status. Moreover, the results showed that breast cancer patients with VM-positive have a shorter overall survival than those with VM-negative (HR=0.23, 95% CI=0.08-0.38,P=0.003). In summary, VM was associated with more aggressive tumor phenotype and poor prognosis in patients with breast cancer. Developing strategies against the VM formation would be a promising therapeutic approach to breast cancer.

Urine miR-21-5p as a potential non-invasive biomarker for gastric cancer.

Many reports have implicated that microRNAs involve in cancer development and progression, such as miR-155 in breast cancers and miR-196 in gastric cancers. Furthermore, microRNAs are more stable than typical protein-coding gene mRNAs in varieties of clinical samples including body fluids. This suggests that they are potentially valuable biomarkers for cancer monitoring. In this study, we have used urine samples of gastric cancer patients to demonstrate the feasibility of urine microRNAs for gastric cancer detection. Urine samples of gastric cancer patients were extracted for total RNA, which were examined for the expression of miR-21-5p using quantitative stem-loop PCR. Our results demonstrated that miR-21-5p could be detected in small amounts of urine samples with good stability, and the expression levels of miR-21-5p were reduced following surgical removal of gastric cancer tissues. These results implicate that urine miR-21-5p could be utilized as a novel non-invasive biomarker of gastric cancer detection and monitoring.

Androgen receptor expression identifies patient with favorable outcome in operable triple negative breast cancer.

In this study we sought to investigate the prevalence and prognostic value of androgen receptor (AR) status in operable triple-negative breast cancer (TNBC) patients. We collected the clinical data of 360 patients with TNBC, and found a positivity AR expression of 31.4% with a cut-off value of 10%. Tumors expressing the negative CK5/6 (P=0.013) and low Ki-67 (P=0.007) are more likely to have positive AR. In multivariate survival analysis, AR expression is correlated with increased DFS (HR=0.467, 95%CI 0.271-0.805; P=0.006) and OS (HR=0.488, 95%CI 0.267-0.894, P=0.020) independently. In addition, patients with AR+ tumors are more likely to have favorable outcome in patients with young, pre-menopausal, large tumor size, more node involvement (4+), high stage, high grade, vascular invasion+, P53+, CK5/6-, and higher Ki-67. Our study has indicated that the absence of AR might help to identify patients with relatively higher risk of disease relapse and death, and further clinical studies of anti-androgen agents are warranted to enrich the therapeutic strategy options for AR+ TNBCs.

Concordance of genomic alterations by next-generation sequencing (NGS) in tumor tissue versus circulating tumor DNA in breast cancer.

While identifying genomic alterations in tumor tissue is the current gold-standard technique for molecular profiling, circulating tumor DNA (ctDNA) represents a non-invasive method of assessing genomic alterations using peripheral blood. The concordance of genomic alterations between two commercially-available ctDNA and tissue biopsies was compared in 45 patients with breast cancer using paired next-generation sequencing tissue and ctDNA biopsies. Across all genes, concordance between the two platforms was 91.0-94.2%. When only considering genomic alterations in either assay (e.g., excluding wild type/wild type genes), concordance was 10.8-15.1% with full plus partial concordance of 13.8-19.3%. Concordant mutations were associated with significantly higher variant allele frequency. Over half of mutations detected in either technique were not detected using the other biopsy technique. Including variants of unknown significance, the average number of alterations per patient was significantly higher for tissue (4.56) compared to ctDNA (2.16). When eliminating alterations not detectable in the ctDNA assay, mean number of alterations for tissue and ctDNA was similar (2.67 for tissue, 2.16 for ctDNA). Across five representative genes (TP53, PIK3CA, ERBB2, BRCA1, BRCA2), sensitivity and specificity were 35.7% and 95.0%, respectively. Concordance when genomic alterations were detected in either tissue or ctDNA was low with each technique detecting a significant amount of non-overlapping mutations. Potential explanations for the lack of concordance include tumor heterogeneity, different sequencing techniques, spatial and temporal factors, and potential germline DNA contamination. The study indicates that both tissue and blood-based NGS may be necessary to describe the complex biology of breast cancer.