Estrogen Receptor Negative Research Articles

Predictive and prognostic value of EPIC1 in patients with breast cancer receiving neoadjuvant chemotherapy.

Background:EPIC1 is an oncogenic long non-coding ribonucleic acid (RNA) that promotes cell growth and cell-cycle progression and inhibits apoptosis in several cancer cell lines. However, clinical studies on EPIC1 in breast cancer, specifically in the neoadjuvant setting, are relatively few.Methods:Patients treated with weekly paclitaxel–cisplatin-based neoadjuvant chemotherapy after core-needle biopsy were included in the study. Real-time quantitative polymerase chain reaction assays were performed to detect EPIC1 expression.Results:Among all patients included in this study (n = 111), higher EPIC1 expression was associated with estrogen receptor negativity, human epidermal growth factor receptor 2 positivity, higher Ki67 index, and higher histologic grade. Multivariate analysis suggested that EPIC1 expression was an independent predictive factor for pathological complete response, with a significant interaction between EPIC1 expression and age. The Kaplan–Meier Plotter dataset suggested that the EPIC1 high-expression group showed a worse 10-year distant metastasis-free survival and post-progression survival when compared with the EPIC1 low-expression group. The Cancer Genome Atlas dataset suggested that the overall survival in the EPIC1 high-expression group was inferior to that in the EPIC1 low-expression group, specifically in hormone receptor (HorR)-positive patients and patients aged <50 years. Pathway analysis revealed the top pathways that indicated the potential mechanisms of EPIC1 in chemoresistance, including the daunorubicin and doxorubicin metabolic processes.Conclusions:Our study suggests that EPIC1 may be a promising biomarker for both neoadjuvant chemosensitivity and long-term clinical outcomes in breast cancer, specifically in the HorR-positive premenopausal subgroup. It may also help identify candidate responders and determine treatment strategies.

Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome.

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer.Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point.Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival.Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.

Correlation between the presence of androgenic receptors and molecular and histopathological variables in breast cancer

Introduction: The expression of androgenic receptors (AR) is a new predictive marker of response and prognosis in invasive breast carcinoma (BC). It emerges as a potential therapeutic target. Objective: To evaluate the frequency of AR positivity and its correlation with molecular and histopathological parameters in infiltrative BC. Method: Retrospective cohort study, analyzing 119 cases of invasive non-metastatic BC, seen at a private clinic. Hormonal receptors were screened by immunohistochemical reaction, and AR were considered positive when present in at least 10% of cells, ER and PR from 1%. This finding was correlated with pathological staging, histological grade (HG), vascular-lymphatic invasion (VLI), estrogen (ER) and progesterone receptors (RP), HER2 and Ki 67. Results: Androgen receptors were positive in 80.6% of cases. In the assessment of pathological staging, of the 63 patients with stage I, 81% showed positive androgen receptors, while among the 28 patients with stage II, 75% had positive androgen receptors, and 88% of the 17 patients with stage III presented the positivity of the recipient. Regarding the histological parameters of the tumor, 16 patients had grade 1 tumors, 93.7% of them with positive androgen receptors, while among the 63 with grade 2 tumors 90.4% had androgen receptor positivity, and only 59, 3% of the 27 tumors evaluated as grade 3 had a positive androgen receptor. The vascular-lymphatic invasion was negative in 57 patients, 78.9% of the tumors with positive androgen receptor. Among the 56 tumors with positive vascular-lymphatic invasion, 85.7% had an androgen receptor positivity. In the immunohistochemical evaluation of tumors, among the 95 patients with positive estrogen receptors, 91.5% also had positive androgen receptor, which was positive in only 37.5% of the 24 patients with negative estrogen receptors. Of the 21 patients who had tumors with overexpressed HER, 85.7% also had positive androgen receptors, which were also positive in 86.4% of 96 without overexpression of HER2. In the evaluation of cell proliferation by the Ki67 antigen, among the 50 tumors with Ki67 &lt;20%, 94% had positive androgen receptors, while 83.7% were positive among the 49 tumors with Ki67 between 20 and 50% and only 35% positivity of androgen receptors in 17 tumors with Ki67&gt; 50%. Conclusions: AR positivity is associated with more differentiated hormone-dependent tumors with a lower proliferation rate.

Importance of MACC1 expression in breast cancer and its relationship with pathological prognostic markers.

Metastasis associated colon cancer gene 1 (MACC1) is a gene that was first described as a c-Met transcription regulator causing the progression of colon cancer. In this study, protein and messenger RNA (mRNA) expression of MACC1 in breast cancer and its relationship with clinicopathological prognostic parameters were investigated. Sixty-six cases with tumors underwent radical mastectomy for invasive ductal carcinoma and 25 control cases operated for mammoplasty were included in the study. In paraffin blocks of tumor and control tissues, MACC1 expression was investigated by the immunohistochemical method and Real-time polymerase chain reaction (Real-Time PCR). In addition, vascular endothelial growth factor (VEGF) expression was examined immunohistochemically in tumor tissues. The relationship between MACC1 expression in tumor tissues, clinicopathological prognostic parameters, and VEGF was investigated. In this study, protein and mRNA expressions of MACC1 were found to be higher in tumor tissues compared with normal breast tissues. MACC1 protein expression was also associated with significant poor prognostic markers, such as high histologic grade, ER negativity, and HER2 positivity. However, there was no correlation between MACC1 expression and VEGF. According to these results, MACC1 expression may be a marker of breast carcinoma as well as an independent predictor of poor prognosis. In addition, MACC1 may not affect angiogenesis in breast cancer or even if it has an effect, it may not be associated with VEGF. However, it would be appropriate to support these results in a larger series by investigating in vivo and in vitro studies.

The Clinicopathological Significance of Basal Markers in Early-Stage Invasive Carcinoma of No Special Type of the Breast.

Basal markers [cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR)] are used in identifying the basal-like breast carcinoma subtype, which is associated with a poor prognosis. However, the clinicopathological significance in early-stage invasive carcinoma of no special type (IC, NST) has not been well established. In a five-year period, 133 female patients with early-stage IC, NST with a median follow-up time of 89 months were included. The immunohistochemistry-based molecular subtypes were identified according to ASCO/CAP guidelines in 2013. The cutoff values for basal positivity were determined as 10% for each marker. Basal positivity was recorded in 83.3% (5/6) of triple-negative breast cancers, 50% (2/4) of HER2-enriched, 18.6% (13/70) of luminal B, and 8.3% of luminal A (4/48) subtype. CK5/6 and EGFR positivity were significantly associated with ER negativity (p < 0.001). EGFR positive cases were significantly associated with PR negativity and HER2 positivity compared to negative cases. However, basal positivity was not associated with the patient outcome (p = 0.006 and p = 0.004, respectively). Basal positive IC, NSTs were associated with hormone receptor negativity and HER2 overexpression; these patients would therefore be less likely to respond to hormonotherapy and more likely to benefit from anti-HER2 treatment as well as dual-kinase inhibitors. The lack of standardization of the definition of basal marker positivity may contribute to the conflicting results of prognostic studies. Hence, further studies focusing on developing a standard protocol for determining basal marker positivity are needed not only for IC, NST but also for other histological types of breast cancer.

Quantitative digital image analysis of tumor-infiltrating lymphocytes in HER2-positive breast cancer.

As visual quantification of the density of tumor-infiltrating lymphocytes (TILs) lacks in precision, digital image analysis (DIA) approach has been applied in order to improve. In several studies, TIL density has been examined on hematoxylin and eosin (HE)-stained sections using DIA. The aim of the present study was to quantify TIL density on HE sections of core needle biopsies using DIA and investigate its association with clinicopathological parameters and pathological response to neoadjuvant chemotherapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The study cohort comprised of patients with HER2-positive breast cancer, all treated with neoadjuvant anti-HER2 therapy. DIA software applying machine learning-based classification of epithelial and stromal elements was used to count TILs. TIL density was determined as the number of TILs per square millimeter of stromal tissue. Median TIL density was 1287/mm2 (range, 123-8101/mm2). A high TIL density was associated with higher histological grade (P = 0.02), estrogen receptor negativity (P = 0.036), and pathological complete response (pCR) (P < 0.0001). In analyses using receiver operating characteristic curves, a threshold TIL density of 2420/mm2 best discriminated pCR from non-pCR. In multivariate analysis, high TIL density (> 2420/mm2) was significantly associated with pCR (P < 0.0001). Our results indicate that DIA can assess TIL density quantitatively, machine learning-based classification algorithm allowing determination of TIL density as the number of TILs per unit area, and TIL density established by this method appears to be an independent predictor of pCR in HER2-positive breast cancer.

The association between chemotherapy-induced febrile neutropenia and breast cancer subtype in Japanese patients.

Background Chemotherapy-induced febrile neutropenia is a common and potentially lethal side effect; therefore, predicting febrile neutropenia development is important. Objective This study examined the risk factors for febrile neutropenia development according to breast cancer subtype among Japanese patients receiving chemotherapy. Methods This single-center retrospective study evaluated 60 outpatients who received chemotherapy for breast cancer (epirubicin plus cyclophosphamide or docetaxel plus cyclophosphamide). Their characteristics were evaluated to identify factors associated with febrile neutropenia development. Results Thirty-three patients developed febrile neutropenia and 27 patients did not. The risk of developing febrile neutropenia was significantly associated with estrogen receptor negativity (p < 0.05). Logistic regression analysis further confirmed that estrogen receptor negativity was an independent risk factor for febrile neutropenia development (odds ratio: 4.35, 95% confidence interval: 1.05-18.0). Moreover, the highest rate of febrile neutropenia was observed in patients with hormone receptor (estrogen and/or progesterone receptor)-negative/human epidermal growth factor receptor 2-positive breast cancer. Conclusion In addition to the known risk factors for febrile neutropenia, our findings revealed that the risk of developing chemotherapy-induced febrile neutropenia is associated with the hormone receptor-negative/human epidermal growth factor receptor 2-positive subtype in Japanese patients with breast cancer.

Shear-Wave Elastography of the Breast: Added Value of a Quality Map in Diagnosis and Prediction of the Biological Characteristics of Breast Cancer.

ObjectiveTo determine the added value of a shear-wave elastography (SWE) quality map (QM) in the diagnosis of breast lesions and in predicting the biological characteristics of invasive breast cancer.Materials and MethodsBetween January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWVmean), max SWV (SWVmax), and standard deviation (SD) with QM guidance (SWVmean + QM, SWVmax + QM, and SD + QM, respectively) and without QM guidance (SWVmean − QM, SWVmax − QM, and SD − QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance.ResultsOf the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWVmean + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWVmean − QM (3.29 ± 1.22 m/s) and SD − QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWVmean + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWVmean − QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD − QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWVmean + QM (all p < 0.05), while only lymphovascular involvement showed higher SWVmean − QM (p = 0.036).ConclusionThe use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.

Integrin α11β1 is expressed in breast cancer stroma and associates with aggressive tumor phenotypes

Cancer‐associated fibroblasts are essential modifiers of the tumor microenvironment. The collagen‐binding integrin α11β1 has been proposed to be upregulated in a pro‐tumorigenic subtype of cancer‐associated fibroblasts. Here, we analyzed the expression and clinical relevance of integrin α11β1 in a large breast cancer series using a novel antibody against the human integrin α11 chain. Several novel monoclonal antibodies against the integrin α11 subunit were tested for use on formalin‐fixed paraffin‐embedded tissues, and Ab 210F4B6A4 was eventually selected to investigate the immunohistochemical expression in 392 breast cancers using whole sections. mRNA data from METABRIC and co‐expression patterns of integrin α11 in relation to αSMA and cytokeratin‐14 were also investigated. Integrin α11 was expressed to varying degrees in spindle‐shaped cells in the stroma of 99% of invasive breast carcinomas. Integrin α11 co‐localized with αSMA in stromal cells, and with αSMA and cytokeratin‐14 in breast myoepithelium. High stromal integrin α11 expression (66% of cases) was associated with aggressive breast cancer features such as high histologic grade, increased tumor cell proliferation, ER negativity, HER2 positivity, and triple‐negative phenotype, but was not associated with breast cancer specific survival at protein or mRNA levels. In conclusion, high stromal integrin α11 expression was associated with aggressive breast cancer phenotypes.

The differences of clinicopathologic characteristics among subgroups of reclassified HER2 fluorescence in situ hybridization (FISH) according to the ASCO/CAP 2018 breast cancer HER2 testing guidelines

AimsThe aim of this study is to analyse differences in clinicopathologic features among reclassified human epidermal growth factor receptor-2 (HER2) fluorescence in situ hybridization (FISH) results in breast cancers according...

Clinicopathological values of PD-L1 expression in HER2-positive breast cancer

Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.

Cytokeratin 7-negative and GATA binding protein 3-negative breast cancers: Clinicopathological features and prognostic significance

BackgroundCytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.MethodsThis study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.ResultsCK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.ConclusionsThis is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.

33P - Contrast enhanced chest CT in patients with breast cancer: Comprehensive imaging analysis and correlation with biological markers

BackgroundTo investigate the feasibility of virtual monoenergetic images (VMIs) derived from a dual-layer detector spectral CT (SDCT) in patients with breast cancer by assessing tumor conspicuity in comparison with conventional images (CI) and to correlate tumor conspicuity on VMIS with prognostic biomarkers. Methods64 patients with pathologically proven benign or breast cancers (14 benign lesions and 65 breast cancers) underwent arterial and 90s delayed phase scan on a SDCT for tumor staging between June 2016 and May 2018. CI were reconstructed at 120kVp, and VMI at 40 keV (VMI40). A retrospective spectral data analysis was performed to assess the regions of interest by using CI and VMI40 on arterial and delayed images (CIART, VMI40ART, CIDE, and VMI40DE). Two radiologists independently reviewed the 4 image sets for the conspicuity score of breast lesions. For quantitative analysis, measurement of Hounsfield units (HU) of breast lesions on VMI40ART and VMI40DE was performed. Receiver operating characteristic (ROC) analysis was performed. Estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, conspicuity score and mean HU of malignant lesions were correlated with histological characteristics. ResultsThe mean conspicuity score of malignant lesions was significantly higher compared with that of benign lesions in all image sets (P < 0.05). The area under the ROC curve of conspicuity score for malignant lesions were greatest on VMI40DE. VMI40DE yielded significantly higher mean HU of malignant lesions compared to VMI40ART (P < 0.001). Malignant lesions on VMI40ART and VMI40DE revealed significantly higher mean HU compared to those of benign lesions (P < 0.001). The conspicuity score and the mean HU on VMI40ART were significantly higher in cancers with diameter greater than 2 cm, ER negativity, PR negativity, and Ki67 positivity (P < 0.05). ConclusionsVMI40DE is feasible to diagnose breast cancers with higher conspicuity score and better contrast enhancement compared with VMI40ART. Moreover, VMI40ART may serve as additional predictors of a poor breast cancer prognosis. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

The BRCA1 c.4096+3A>G Variant Displays Classical Characteristics of Pathogenic BRCA1 Mutations in Hereditary Breast and Ovarian Cancers, But Still Allows Homozygous Viability.

Mutations in BRCA1 result in predisposal to breast and ovarian cancers, but many variants exist with unknown clinical significance (VUS). One is BRCA1 c.4096+3A>G, which affects production of the full-length BRCA1 transcript, while augmenting transcripts lacking most or all of exon 11. Nonetheless, homozygosity of this variant has been reported in a healthy woman. We saw this variant cosegregate with breast and ovarian cancer in several family branches of four Icelandic pedigrees, with instances of phenocopies and a homozygous woman with lung cancer. We found eight heterozygous carriers (0.44%) in 1820 unselected breast cancer cases, and three (0.15%) in 1968 controls (p = 0.13). Seeking conclusive evidence, we studied tumors from carriers in the pedigrees for wild-type-loss of heterozygosity (wtLOH) and BRCA1-characteristic prevalence of estrogen receptor (ER) negativity. Of 15 breast and six ovarian tumors, wtLOH occurred in nine breast and all six ovarian tumours, and six of the nine breast tumors with wtLOH were ER-negative. These data accord with a pathogenic BRCA1-mutation. Our findings add to the current knowledge of BRCA1, and the role of its exon 11 in cancer pathogenicity, and will be of use in clinical genetic counselling.

Integrated Bioinformatics Data Analysis Reveals Prognostic Significance Of SIDT1 In Triple-Negative Breast Cancer.

BackgroundTriple-negative breast cancer (TNBC) is a heterogeneous disease with a worse prognosis. However, current therapies have rarely improved the outcome of patients with TNBC. Here we sought to identify novel biomarkers or targets for TNBC.Materials and methodsPatients GSE76275 clinic traits and their corresponding mRNA profiles for 198 TNBC and 67 non-TNBC were obtained from the GEO database. Weighted gene co-expression network analysis (WGCNA) of the GSE76275 keyed out hub genes, and the differentially expressed genes (DEGs) were identified with the cut-off of adjusted P (adj. P) <0.01 and |log2 fold-change (FC)| > 1.5. The hub - DEGs overlapping genes, as key genes, were considered for further study using Kaplan-Meier plotter online analysis. Subsequently, Breast Cancer Gene-Expression Miner v4.0 and tissue microarray analysis were applied to determine the transcriptional and translational levels of every key gene. Following plasmid transfection for overexpression, the proliferation of TNBC cells was determined by CCK8 and colony formation assay. Moreover, xenograft tumor models were canvassed to investigate their effect upon in vivo tumor growth.ResultsFour genes (SIDT1, ANKRD30A, GPR160, and CA12) were found to be associated with relapse-free survival (RFS) in TNBC through WGCNA and DEGs integrated analysis. Patients with a higher level of SIDT1 had significantly better RFS compared to those with lower levels. The transcriptional and translational levels of SIDT1 were validated as downregulated in patients with triple-negative status, negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Furthermore, SIDT1 inhibited proliferation of breast cancer cells (MDA-MB-231 and MDA-MB-468) and xenograft studies demonstrated that SIDT1 can suppress tumor growth in vivo.ConclusionThis study suggests that SIDT1 may play a crucial role in TNBC progression and has the potential as a prognostic biomarker of TNBC.

276P - The prognostic significance of preoperative tumour marker (CEA, CA15-3) elevation in breast cancer patients

BackgroundTumour markers are widely used for screening and monitoring cancers. CA 15-3 and CEA are FDA-approved tumour markers for monitoring breast cancer. However, the prognostic efficacy of preoperative elevation of CEA and CA15-3 levels in breast cancer remains controversial. MethodsWe retrospectively analyzed the clinicopathological parameters and preoperative serum CEA and CA 15-3 level of 149,238 patients of Korean Breast Cancer Society Registry (KBCSR) Database who underwent surgery between January 2000 and December 2015. ResultsThe patients with elevated CA 15-3/CEA level had shown more advanced T stage and N stage, ER negativity, PR negativity and HER2 positivity compared the patients with normal CA15-3/CEA levels. The patients with elevated CA 15-3/CEA level had worse OS than the patients with normal CA 15-3/CEA level. In survival analysis, both elevated group had worst prognosis compared other groups. In subgroup analysis by subtypes, in luminal A, both elevated group had hazard ratio (HR) 2.14 (95% CI 1.01-4.55), only CA 15-3 elevated had HR 2.38 (95% CI 1.58-3.58) and only CEA elevated group had HR 1.79 (95% CI, 1.20-2.68), compared normal group. In luminal B, both elevated group had HR 3.99 (95% CI 2.23-7.16), only CA 15-3 elevated had HR 2.38 (95% CI 1.58-3.58) and only CEA elevated group had HR 1.79 (95% CI, 1.20-2.68), compared normal group. In HER2 subtype group, elevated CEA level was the only independent prognostic factor. However, in TNBC, elevated preoperative CEA and CA 15-3 level were not a significant prognostic factor for OS. ConclusionsThe elevation of preoperative tumor markers was associated with aggressive characteristic and worse overall survival. Preoperative tumor markers predicted the prognosis of the patients and showed differences according to subtypes. In luminal breast cancer, the CA 15-3 elevation has higher hazard ratio than the CEA elevation and the patients with both tumor markers showed the worst prognosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Up-regulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) is linked to poor prognosis in breast cancer.

Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated with various cancer types. Here we analyzed by immunohistochemistry its expression in 2,197 breast cancers. LPCAT1 staining was found in 97.8% of 1,774 interpretable tumors, including 48.1% with weak, 28.7% with moderate, and 14.4% with strong expression. The frequency of LPCAT1 positivity depended on the histological tumor type. Moderate or strong LPCAT1 positivity was more common in cancers of no special type (NST) (46.2%) than in lobular carcinomas (25.9%; p<0.0001). Strong LPCAT1 was associated with BRE grade, tumor cell proliferation and overall survival in all cancers and in the subgroup of NST cancers (p<0.0001, each). In the subset of NST cancers the prognostic effect of LPCAT1 expression was independent of pT, and BRE grade (p<0.0001 each). A comparison with molecular features showed that LPCAT1 was strongly associated with estrogen receptor negativity (p<0.0001), progesterone receptor negativity (p<0,0001), amplification of HER2 (p<0.0001) and MYC (p=0.0066), as well as deletions of PTEN (p<0.0001) and CDKNA2 (p=0.0151). It is concluded that LPCAT1 overexpression is linked to adverse tumor features and poor prognosis in breast cancer. These data also highlight the important role of lipid metabolism in breast cancer biology.

Comparison of Survival Outcomes in Medullary Carcinoma and Invasive Ductal Carcinoma of the Breast

Aim: To compare clinicopathological characteristics and prognoses of medullary carcinoma (MC) and invasive ductal carcinoma (IDC) of the breast. Patients &amp; methods: We screened patients from the SEER database. Kaplan–Meier analysis and Cox proportional hazards models were used to investigate influence on survival. Propensity score matching analysis was performed to reduce possible bias. Results: Compared with IDC, MC tended to be younger patients, poor differentiation, negative estrogen receptor and progesterone receptor and chemotherapy. Better overall survival and disease-specific survival were observed in MC patients than in IDC patients. It shared several prognostic factors. Worse disease-specific survival was observed in IDC patients than in MC patients (HR: 1.590; 95% CI: 1.475–1.714; p &lt; 0.001). Conclusion: The clinical features and outcomes had evident differences between MC and IDC patients. These findings will provide more information for the prognosis of MC and IDC.

Potential prognostic value of PD-L1 and FOXP3 as predictors of relapse in breast cancer

Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p = .003), basal-like subtype(p = .001), high Ki67(p = .001), negative ER status(p = .001), negative PR(p = .028), HER2 expression(p = .04), advanced stage (p = .001), and LN metastases(p = .001). For PDL1, only statistically significant correlation with high Ki67 (p = .018) and advanced stage(p = .03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p= .001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p = .054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.

Polymorphisms in Survivin (BIRC5 Gene) Are Associated with Age of Onset in Breast Cancer Patients

Survivin, encoded by BIRC5 gene (baculoviral IAP repeat containing 5), belongs to the family of inhibitors of apoptosis proteins (IAPs). In mammalian cells it participates in the control of mitosis, apoptosis regulation, and cellular stress response. Its expression is increased in almost all types of cancers. The aim of this study was to investigate the role of BIRC5 polymorphisms in breast cancer (BC) and to connect survivin expression with various clinicopathological characteristics of BC patients. Blood and archival tumour tissue samples were collected from 26 BC patients from Croatia. Survivin expression was determined immunohistochemically. BIRC5 promoter, coding region, and 3'UTR were genotyped. DNA from 74 healthy women was used as control. BIRC5 polymorphisms and survivin expression were tested against age of onset, histological grade, tumour type and size, lymph node status, oestrogen, progesterone, Her2, and Ki67 status. Numbers of samples with weak, moderate, and strong survivin expression were 9 (33.3%), 11 (40.7%), and 7 (25.9%), respectively. Most patients had nuclear survivin staining (92.6%). High survivin expression was significantly associated with negative oestrogen receptor status (p=0.007) and positive Ki67 expression (p=0.032). Ki67 expression was also positively correlated with histological grade (p=0.0009). Fourteen polymorphisms were found in BC samples, located mostly in promoter and 3'UTR of BIRC5. There was no significant difference in the distribution of polymorphisms between BC and control samples. Among clinicopathological characteristics of BC patients, alleles of five BIRC5 polymorphisms were associated with younger age of onset: c.-644T>C (55.8 years [y] vs. 48.1 y; p=0.006), c.-241C>T (54.2 y vs. 45.0; p=0.029), c.9809T>C (55.8 y vs. 48.1 y; p=0.006), c.-1547C>T (58.3 y vs. 50.9 y; p=0.011), and c.9386T>C (50.8 y vs. 59.5 y; p=0.004). To assess the significance of BIRC5 polymorphisms and survivin expression as predictive and prognostic biomarkers for BC further research with a larger sample size is needed.