Chemotherapy-elicited exosomal miR-378a-3p and miR-378d to promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12615-e12615
Author(s):  
Jin Zhang
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Chemotherapeutic Agents ◽  
Cell Counting ◽  
Chemotherapy Response ◽  
Mouse Tumor ◽  
Response To Chemotherapy ◽  
Serum Exosomes

e12615 Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemo-elicited exosomes in regulating chemoresistance is poorly understood. Methods: Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Results: Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome induced drug resistance in a nude mouse tumor xenograft model. Conclusions: This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

scholarly journals Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Qianxi Yang ◽  
Shaorong Zhao ◽  
Zhendong Shi ◽  
Lixia Cao ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Chemotherapeutic Agents ◽  
Cell Counting ◽  
Chemotherapy Response ◽  
Mouse Tumor ◽  
Response To Chemotherapy ◽  
Serum Exosomes

Abstract Background Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemotherapy-elicited exosomes in regulating chemoresistance is poorly understood. Methods Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Results Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome-induced drug resistance in a nude mouse tumor xenograft model. Conclusion This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of the WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

scholarly journals Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xu Yang ◽  
Geng-Xi Cai ◽  
Bo-Wei Han ◽  
Zhi-Wei Guo ◽  
Ying-Song Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cell Receptor ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Plasma Dna ◽  
Transcription Start Sites ◽  
Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer

2010 ◽  
Vol 28 (1) ◽  
pp. 105-113 ◽  
Author(s):  
Carsten Denkert ◽  
Sibylle Loibl ◽  
Aurelia Noske ◽  
Marc Roller ◽  
Berit Maria Müller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Validation Cohort ◽  
Independent Predictor ◽  
Pathologic Complete Response ◽  
Marker Genes ◽  
Cancer Tissue ◽  
Chemotherapy Response ◽  
Training Cohort ◽  
Response To Neoadjuvant Chemotherapy

Purpose Preclinical data suggest a contribution of the immune system to chemotherapy response. In this study, we investigated the prespecified hypothesis that the presence of a lymphocytic infiltrate in cancer tissue predicts the response to neoadjuvant chemotherapy. Methods We investigated intratumoral and stromal lymphocytes in a total of 1,058 pretherapeutic breast cancer core biopsies from two neoadjuvant anthracycline/taxane-based studies (GeparDuo, n = 218, training cohort; and GeparTrio, n = 840, validation cohort). Molecular parameters of lymphocyte recruitment and activation were evaluated by kinetic polymerase chain reaction in 134 formalin-fixed, paraffin-embedded tumor samples. Results In a multivariate regression analysis including all known predictive clinicopathologic factors, the percentage of intratumoral lymphocytes was a significant independent parameter for pathologic complete response (pCR) in both cohorts (training cohort: P = .012; validation cohort: P = .001). Lymphocyte-predominant breast cancer responded, with pCR rates of 42% (training cohort) and 40% (validation cohort). In contrast, those tumors without any infiltrating lymphocytes had pCR rates of 3% (training cohort) and 7% (validation cohort). The expression of inflammatory marker genes and proteins was linked to the histopathologic infiltrate, and logistic regression showed a significant association of the T-cell–related markers CD3D and CXCL9 with pCR. Conclusion The presence of tumor-associated lymphocytes in breast cancer is a new independent predictor of response to anthracycline/taxane neoadjuvant chemotherapy and provides useful information for oncologists to identify a subgroup of patients with a high benefit from this type of chemotherapy.

scholarly journals MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

2013 ◽  
Vol 34 (6) ◽  
pp. 387-393 ◽  
Author(s):  
Mohsen Taheri ◽  
Frouzandeh Mahjoubi
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Histological Grade ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Response To Chemotherapy ◽  
Mrp1 Expression

A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor.

Clinicopathologic profile of breast cancer patients treated with neoadjuvant chemotherapy at HUCFF/UFRJ

Mastology ◽  
2021 ◽  
Author(s):  
Luís Claudio Belo Amendola ◽  
Maria de Fatima Dias Gaui ◽  
Ana Helena Pereira Correia Carneiro ◽  
Nathalie Henriques Silva Canedo
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Pathologic Complete Response ◽  
Real Life ◽  
Public University ◽  
Public Institution ◽  
Breast Cancer Patients ◽  
Response To Chemotherapy

Introduction: The objective of this study is to describe the profile of patients from a public institution, submitted to neoadjuvant chemotherapy (NACT), comparing the verified pathological response with literature data. Methods: Observational retrospective cohort study on breast cancer patients diagnosed between September 2001 and October 2018 and treated with NACT at Hospital Universitário Clementino Fraga Filho (HUCFF/UFRJ), located in Rio de Janeiro, Brazil. The adopted neoadjuvant chemotherapy regimen was based on anthracycline and docetaxel. Results: A total of 133 patients were evaluated. The average age in this group was 54 years (28-86), 49 women (37%) were under 50 years old. The following distribution by molecular subtype was observed: overexpression or amplification of the human epidermal growth factor receptor 2 (HER2+) (13 women, 26.6%), Luminal (19 women, 38.8%), and Triple-negative (TN) (17 women, 34.6%). The HER2+ and TN subtypes had a higher incidence of cases between 40-49 years and 50-59 years. As for the initial staging, 34% were IIIA; 26%, IIB; and 19%, IIIB. Only one patient did not undergo surgery after NACT, 33 (24.8%) underwent conservative surgery, and 99 patients (74.4%) underwent mastectomy. Regarding the axillary approach, 41 (31%) underwent sentinel lymph node biopsy and 88 (66%) had an indication for lymphadenectomy. In the anatomopathological evaluation of the surgery, 12 (9.1%) patients obtained a pathologic complete response (pCR) and 113 (84.9%), partial or no response to chemotherapy. Conclusion: This research enabled the identification of clinicopathologic characteristics and outcome of patients who received neoadjuvant chemotherapy in a public university service. The predominance of advanced tumors was observed, stressing the need for public health policies for the screening of breast cancer as well as the guarantee of timely treatment for diagnosed cases. The data somewhat reflect the difficulty that the public sector encounters to carry out the most appropriate treatment. The authors expect that this article, by analyzing the profile and the adopted treatment in real-life cases and in a public university institution, can contribute to the improvement of breast cancer treatment in Brazil.

scholarly journals Multi-Center Evaluation of Artificial Intelligent Imaging and Clinical Models for Predicting Neoadjuvant Chemotherapy Response in Breast Cancer

2021 ◽  
Author(s):  
Tan Hong Qi ◽  
Ong Hiok Hian ◽  
Arjunan Muthu Kumaran ◽  
Tira J. Tan ◽  
Ryan Shea Tan Ying Cong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Chemotherapy Response ◽  
Clinical Parameters ◽  
Model Based ◽  
Response To Chemotherapy ◽  
Clinical Models

Abstract Background: Neoadjuvant chemotherapy (NAC) plays an important role in the management of locally advanced breast cancer. It allows for downstaging of tumours, potentially allowing for breast conservation. NAC also allows for in-vivo testing of the tumours’ response to chemotherapy and provides important prognostic information. There are currently no clearly defined clinical models that incorporate imaging with clinical data to predict response to NAC. Thus, the aim of this work is to develop a predictive AI model based on routine CT imaging and clinical parameters to predict response to NAC. Methods: The CT scans of 324 patients with NAC from multiple centers in Singapore were used in this study. Four different radiomics models were built for predicting pathological complete response (pCR): first two were based on textural features extracted from peri-tumoral and tumoral regions, the third model based on novel space-resolved radiomics which extract feature maps using voxel-based radiomics and the fourth model based on Deep Learning (DL). Clinical parameters were included to build a final prognostic model. Results: The best performing models were based on space-resolved and deep learning approaches. Space-resolved radiomics improves the clinical AUCs of pCR prediction from 0.743 (0.650 to 0.831) to 0.775 (0.685 to 0.860) and our DL model improved it from 0.743 (0.650 to 0.831) to 0.772 (0.685 to 0.853). The tumoral radiomics model performs the worst with no improvement of the AUC from the clinical model. The peri-tumoral combined model gives moderate performance with an AUC of 0.765 (0.671 to 0.855). Conclusions: Radiomics features extracted from diagnostic CT augments the predictive ability of pathological complete response when combined with clinical features. The novel space-resolved radiomics and deep learning radiomics approaches outperformed conventional radiomics techniques.

Single nucleotide polymorphisms to predict for neoadjuvant chemotherapy in breast cancer according to estrogen receptor (ER) status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 544-544
Author(s):  
Diane Pannier ◽  
Aurelie Dumont ◽  
Emmanuelle Tresch ◽  
Jinying Chen ◽  
Agnes Ducoulombier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Breast Tumors ◽  
Breast Adenocarcinoma ◽  
Chemotherapy Response ◽  
Er Status

544 Background: Neoadjuvant chemotherapy (NCT) using anthracyclines and taxanes is a standard treatment for locally advanced breast cancer and pathologic complete response (pCR) is a major prognostic factor for survival. Gene polymorphisms have been identified as modulators of chemotherapy response. Our study investigated constitutional variants of genes associated with a change in the response to neoadjuvant chemotherapy using taxanes and/or anthracyclines in patients with breast adenocarcinoma. Methods: From November 2007 to January 2012, 118 women with breast adenocarcinoma histologically proven, with no Her2 surexpression, receiving or having received a neoadjuvant chemotherapy with taxanes and/or anthracyclines were included in the study. NCT associated 3 FEC100 then 3 Docetaxel every 21 days. Genotyping of 46 SNPs was performed on germline DNA using real time PCR. pCR was correlated to clinical characteristics and genotypes using univariate logistic regression. Results: 21.2% had a pCR according to Sataloff classification. pCR is increased in SBRIII (p=0.009), estrogen receptor negative (p=0.005) and triple negative (p=0.006) tumors. 7 SNP are significantly associated with pCR in ER+ breast tumors (pCR=13.5%). Among these SNP, pCR is increased for patients carrying almost one G allele for SLCO1B3-rs11045585 (pCR=28.6%; p=0.032), for homozygotes GG for SHTM1-rs1979277 (pCR=24.3%, p=0.006) and for homozygotes CC for CYP1B1-rs1056836 (pCR=25.7%; p=0.003). Moreover, 4 SNPs are significantly associated with pCR in ER- breast tumors: ERCC1-rs11615 (carriers of almost one C allele: pCR=50%; p=0.030), CD24-rs52812045 (Homozygotes CC pCR=56.3%, p=0.033), CYP2B6-rs2279343(carriers of one or two G allele: pCR=52.6%; p=0.046) and GSTP1-rs1695 (carriers of one or two G allele: pCR=48%; p=0.050). Conclusions: Besides ER status, polymorphisms could be useful markers to predict response to anthracyclines/taxanes NCT in breast cancer. Furthermore, this work is the first describing ERCC1-rs11615, SLCO1B3-rs11045585 and SHTM1-rs1979277 as new potential genetic markers for NCT in breast cancer. (The first 3 authors contributed equally to this work.)

Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer (TNBC) in a Peruvian institute.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12038-e12038
Author(s):  
Katerin Ingrid Rojas
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Age At Diagnosis ◽  
Term Survival ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Mean

e12038 Background: TNBC is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 expressions (HER-2). This molecular classification is an excellent prognostic and predictive method in breast cancer (BC). This is an aggressive malignancy with a poor prognosis despite the high rates of response to chemotherapy. Methods: Observational descriptive. We included 165 patients with TNBC stage I-III who received neoadjuvant chemotherapy at National Cancer Institute of Peru from 2000 to 2010. Clinical and pathologic complete response rates, survival measurements, and organ-specific rates of relapse were evaluated. Overall survival (OS) and disease free survival (DFS). Results: The mean age at diagnosis was 48.6 years (range, 24-74 years). The mean size tumor before treatment was 7.7 cm (range, 1-25 cm). One hundred and fifty seven patients (95.2%) had ductal carcinoma. One hundred twenty nine cases (78.2%) were histological grade III. According to T stage, 65 (39.4%) T3 and 83 (50.3%) T4. Thirty four cases (20.6%) were N0. Seventy three patients (44.2%) received AC-Paclitaxel schedule. Thirty four patients (20.6%) had CR to neoadjuvant chemotherapy. There is a significant difference about tumor size before and after neoadjuvant treatment (7.7 vs. 3.6, p<0.05).OS at 5 years for patients with residual disease was 83.5%. In patients with complete response the DFS at 5 years was 55.1%. Locoregional and lung were the most frequent site of recurrence (15.8%) and (13.9%) respectively. According Miller and Paine to grade tumor response, 17 patients(10.3%) I ,33 (20.0%) II, 33 (20.0%) III, 20 (12.1%) IV and 27 (16.4%) V. Node response, 20 patients (12.1%) had type A, 51 (30.9%) type B, 23 (13.9%) type C and 34 (20.6%) type D. Conclusions:These results suggest that most TNBC are in accordance with literature data, especially concerning young age at diagnosis, high grade tumors, advances locally stage at diagnosis, and short time to relapse, high response rate to chemotherapy and excellent OS and DFS. We know it is a heterogeneous disease; however the clinical characteristics still play an important role to predict treatment response and survival.

scholarly journals Tumor apelin and obesity are associated with reduced neoadjuvant chemotherapy response in a cohort of breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Florian Gourgue ◽  
Françoise Derouane ◽  
Cedric van Marcke ◽  
Elodie Villar ◽  
Helene Dano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Response To Chemotherapy ◽  
Two Parameters ◽  
The Impact

AbstractObesity is a known factor increasing the risk of developing breast cancer and reducing disease free survival. In addition to these well-documented effects, recent studies have shown that obesity is also affecting response to chemotherapy. Among the multiple dysregulations associated with obesity, increased level of the apelin adipokine has been recently shown to be directly involved in the association between obesity and increased breast cancer progression. In this study, we analyzed in a retrospective cohort of 62 breast cancer patients the impact of obesity and tumoral apelin expression on response to neoadjuvant chemotherapy. In the multivariate logistic regression, obesity and high tumoral apelin expression were associated with a reduced response to NAC in our cohort. However, obesity and high tumoral apelin expression were not correlated, suggesting that those two parameters could be independently associated with reduced NAC response. These findings should be confirmed in independent cohorts.

scholarly journals Predictive Value of Immune Genomic Signatures from Breast Cancer Cohorts Containing Data for Both Response to Neoadjuvant Chemotherapy and Prognosis after Surgery

2021 ◽  
Author(s):  
Yidan Zhu ◽  
Takayuki Iwamoto ◽  
Yukiko Kajiwara ◽  
Yuko Takahashi ◽  
Mariko Kochi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Breast Cancer Subtypes ◽  
Chemotherapy Response ◽  
Breast Cancer Patients ◽  
Predictive Values ◽  
Cancer Subtypes ◽  
Hormone Receptor Positive ◽  
Response To Chemotherapy

Abstract BackgroundPrevious studies of immune-related gene signatures (IGSs) in breast cancer have attempted to predict the response to chemotherapy or prognosis and were performed using different patient cohorts. The purpose of this study was to evaluate the predictive functions of various IGSs using the same patient cohort that included data for response to chemotherapy as well as the prognosis after surgery.MethodsWe applied five previously described IGS models in a public dataset of 508 breast cancer patients treated with neoadjuvant chemotherapy. The prognostic and predictive values of each model were evaluated, and their correlations were compared.ResultsWe observed a high proportion of expression concordance among the IGS models (r: 0.56-1). Higher gene expression scores of IGSs were detected in aggressive breast cancer subtypes (basal and HER2-enriched) (P < 0.001). Four of the five IGSs could predict chemotherapy responses and two could predict 5-year relapse-free survival in cases with hormone receptor-positive (HR+) tumors. However, the models showed no significant differences in their predictive abilities for hormone receptor-negative (HR-) tumors.ConclusionsIGSs are, to some extent, useful for predicting prognosis and chemotherapy response; moreover, they show substantial agreement for specific breast cancer subtypes. However, it is necessary to identify more compelling biomarkers for both prognosis and response to chemotherapy in HR- and HER2+ cases.

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