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Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

ABSTRACT: Breast cancer stromal compartment, may influence responsiveness to chemotherapy. Our aim was to detect a stromal cell signature (using a direct approach of microdissected stromal cells) associated with response to neoadjuvant chemotherapy (neoCT) in locally advanced breast cancer (LABC). The tumor samples were collected from 44 patients with LABC (29 estrogen receptor (ER) positive and 15 ER negative) before the start of any treatment. Neoadjuvant chemotherapy consisted of doxorubicin and cyclophosphamide, followed by paclitaxel. Response was defined as downstaging to maximum ypT1a-b/ypN0. The stromal cells, mainly composed of fibroblast and immune cells, were microdissected from fresh frozen tumor samples and gene expression profile was determined using Agilent SurePrint G3 Human Gene Expression microarrays. Expression levels were compared using MeV (MultiExperiment Viewer) software, applying SAM (significance analysis of microarrays). To classify samples according to tumor response, the order of median based on confidence statements (MedOr) was used, and to identify gene sets correlated with the phenotype downstaging, gene set enrichment analysis (GSEA). Nine patients presented disease downstaging. Eleven sequences (FDR 17) were differentially expressed, all of which (except H2AFJ) more expressed in responsive tumors, including PTCHD1 and genes involved in abnormal cytotoxic T cell physiology, TOX, LY75, and SH2D1A. The following four pairs of markers could correctly classify all tumor samples according to response: PTCHD1/PDXDC2P, LOC100506731/NEURL4, SH2D1A/ENST00000478672, and TOX/H2AFJ. Gene sets correlated with tumor downstaging (FDR < 0.01) were mainly involved in immune response or lymphocyte activation, including CD47, LCK, NCK1, CD24, CD3E, ZAP70, FOXP3, and CD74, among others. In locally advanced breast cancer, stromal cells may present specific features of immune response that may be associated with chemotherapy response.

SUBMITTER: Katayama MLH

PROVIDER: S-EPMC6953077 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:PurposeWe aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.MethodsMedical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.ResultsOf a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.ConclusionThe pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.

Project description:ImportanceNeoadjuvant therapies have been shown to decrease tumor burden, increase resection rate, and improve the outcomes among patients with locally advanced gastric cancer (GC). However, not all patients are equally responsive; therefore, differentiating potential respondents from nonrespondents is clinically important.ObjectiveTo use pretreatment computed tomography (CT)-pixelated feature-difference extraction techniques to identify diagnostically relevant features that could predict patients' response to neoadjuvant chemotherapy at diagnosis.Design, setting, and participantsThis multicenter cohort study included patients with locally advanced GC who were treated from January 2010 to July 2017 at 2 hospitals in southern China (training cohort) and 1 hospital in northern China (external validation cohort). Their clinicopathological data, pretreatment CT images, and pathological reports were retrieved and analyzed. Data analysis was conducted from December 2017 to May 2021.ExposuresAll patients underwent 2 to 4 cycles of fluorouracil in combination with a platinum-based neoadjuvant chemotherapy regimen. All gastrectomies were performed according to the Japanese Classification of Gastric Carcinoma (14th edition) guidelines.Main outcomes and measuresReliability of clinicopathological and radiomics-based features were assessed with area under receiver operating characteristic curve (AUC) and Mann-Whitney U test.ResultsA total of 323 patients (242 [74.9%] men; median [range] age, 58 [24-82] years) were included in the study, with 250 patients (77.4%) in the training cohort and 73 (22.6%) in the validation cohort. The baseline pretreatment characteristics of the training and validation cohorts were well-balanced. The number of respondents in the training and validation cohort was 122 (48.8%) and 40 (54.8%), respectively, and the number of nonrespondents was 128 (51.2%) and 33 (45.2%), respectively. No clinicopathological variables were significantly associated with treatment response. Using radiomics, 20 low-intercorrelated features from a total of 7477 features were used to construct a radiomics signature that demonstrated significant association with treatment response. Good discrimination performance of the radiomics signature for predicting treatment response in the training (AUC, 0.736; 95% CI, 0.675-0.798) and external validation (AUC, 0.679; 95% CI, 0.554-0.803) cohorts was observed. Decision curve analysis confirmed the clinical utility of the radiomics signature.Conclusions and relevanceIn this study, the proposed radiomics signature showed potential as a clinical aid for predicting the response of patients with locally advanced GC before treatment, thereby allowing timely planning for effective treatments for potential nonrespondents.

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Stromal Cell Signature Associated with Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

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