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      Longitudinal dynamic contrast-enhanced MRI radiomic models for early prediction of response to neoadjuvant systemic therapy in triple-negative breast cancer

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          Abstract

          Early prediction of neoadjuvant systemic therapy (NAST) response for triple-negative breast cancer (TNBC) patients could help oncologists select individualized treatment and avoid toxic effects associated with ineffective therapy in patients unlikely to achieve pathologic complete response (pCR). The objective of this study is to evaluate the performance of radiomic features of the peritumoral and tumoral regions from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquired at different time points of NAST for early treatment response prediction in TNBC. This study included 163 Stage I-III patients with TNBC undergoing NAST as part of a prospective clinical trial (NCT02276443). Peritumoral and tumoral regions of interest were segmented on DCE images at baseline (BL) and after two (C2) and four (C4) cycles of NAST. Ten first-order (FO) radiomic features and 300 gray-level-co-occurrence matrix (GLCM) features were calculated. Area under the receiver operating characteristic curve (AUC) and Wilcoxon rank sum test were used to determine the most predictive features. Multivariate logistic regression models were used for performance assessment. Pearson correlation was used to assess intrareader and interreader variability. Seventy-eight patients (48%) had pCR (52 training, 26 testing), and 85 (52%) had non-pCR (57 training, 28 testing). Forty-six radiomic features had AUC at least 0.70, and 13 multivariate models had AUC at least 0.75 for training and testing sets. The Pearson correlation showed significant correlation between readers. In conclusion, Radiomic features from DCE-MRI are useful for differentiating pCR and non-pCR. Similarly, predictive radiomic models based on these features can improve early noninvasive treatment response prediction in TNBC patients undergoing NAST.

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          Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.

          Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem-like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted "driver" signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies.
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            Pembrolizumab for Early Triple-Negative Breast Cancer

            Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.
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              Triple-negative breast cancer.

              Triple-negative breast cancer, so called because it lacks expression of the estrogen receptor, progesterone receptor, and HER2, is often, but not always, a basal-like breast cancer. This review focuses on its origin, molecular and clinical characteristics, and treatment.
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                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                24 October 2023
                2023
                : 13
                : 1264259
                Affiliations
                [1] 1Department of Imaging Physics, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [2] 2Department of Breast Imaging, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [3] 3Koc University Hospital , Istanbul, Türkiye
                [4] 4Department of Biostatistics, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [5] 5Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [6] 6Department of Pathology, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [7] 7Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [8] 8Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [9] 9Department of Surgery, Baylor College of Medicine , Houston, TX, United States
                [10] 10Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                Author notes

                Edited by: Li Chen, Huazhong University of Science and Technology, China

                Reviewed by: Lu Cao, Shanghai Jiao Tong University, China; Liu Jing, Shandong University, China; Xie Su, Second Affiliated Hospital of Guangxi Medical University, China

                *Correspondence: Jingfei Ma, jma@ 123456mdanderson.org

                †These authors have contributed equally to this work and share senior authorship

                Article
                10.3389/fonc.2023.1264259
                10628525
                bb1b087e-adf3-4534-ab77-bfe4f45bfdc3
                Copyright © 2023 Panthi, Mohamed, Adrada, Boge, Candelaria, Chen, Hunt, Huo, Hwang, Korkut, Lane, Le-Petross, Leung, Litton, Pashapoor, Perez, Son, Sun, Thompson, Tripathy, Valero, Wei, White, Xu, Yang, Zhou, Yam, Rauch and Ma

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 July 2023
                : 09 October 2023
                Page count
                Figures: 4, Tables: 5, Equations: 0, References: 39, Pages: 11, Words: 5750
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Supported by the NIH/NCI under award number P30CA016672 and the resources from the Department of Biostatistics Resource Group were used.
                Categories
                Oncology
                Original Research
                Custom metadata
                Breast Cancer

                Oncology & Radiotherapy
                triple-negative breast cancer,dynamic contrast-enhanced mri,neoadjuvant systemic therapy,radiomic analysis,pathologic complete response

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