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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ENeoadjuvant chemotherapy (NACT) is now widely used in the management of locally advanced breast cancer and in patients with relatively large tumors who are interested in breast conservation. Patients who do not have a complete pathologic complete response typically have poorer outcomes compared with patients with a pCR [Rastogi P et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008]. This article presents molecular profiling data on residual triple-negative breast cancer after NACT.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EAdjuvant\/Neoadjuvant Therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EOncology Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EBreast Cancer\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ENeoadjuvant chemotherapy (NACT) is now widely used in the management of locally advanced breast cancer and in patients with relatively large tumors who are interested in breast conservation. Critical studies have highlighted differences in pathologic complete response (pCR) rates between breast cancer subtypes, with triple-negative breast cancer (TNBC) having a higher pCR rate compared with the other subtypes [Carey LA et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E 2007]. Patients who do not have a complete pCR typically have poorer outcomes compared with patients with a pCR [Rastogi P et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EJustin M. Balko, PharmD, PhD, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA, presented molecular profiling data on residual TNBCs after NACT.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EDr. Balko and colleagues hypothesized that profiling residual TNBCs would identify targetable lesions in the component of the tumor that was resistant to chemotherapy, and these findings may reflect the phenotype of potential micrometastases. The study included tumor samples from 102 patients (median age 48 years) who had clinically defined TNBC with residual disease following NACT. Of the 89 evaluable post-NACT-treated tumors, 64% were basal-like, 19% were human epidermal growth factor 2 (HER2)-enriched, 6% were luminal A, 6% were luminal B, and 5% were normal-like. The most common tumor stage was IIIb (69%), and 33% of the patients were node negative. Half of the patients were premenopausal and 48% were postmenopausal. Immunohistochemistry for Ki67, estrogen receptor, progesterone receptor, HER2, and androgen receptor was conducted on 112 of the samples. Nanostring digital expression analysis of 450 genes was performed in 89 of the samples, and next-generation sequencing (NGS) of 182 oncogenes and tumor suppressors was completed on 81 of the samples.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EA diverse range of genetic aberrations were found in the majority of residual tumors following NACT, including alterations in the PI3K\/mTOR pathway (38%), DNA repair genes (12%), cell cycle genes (38%), Ras\/MAPK pathway (12%), and growth factor receptors (15%). The most common findings were mutations in TP53 (89%) and amplifications of MCL1 and MYC. The antiapoptosis gene MCL1 was amplified in 56% of the tumors, and MYC was amplified in 33%. An interaction between a high MEK activation score and MYC amplification predicted poor recurrence-free survival (RFS).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EJAK2 amplifications were identified in 11% (8\/72) of the patients. Both RFS (p=0.005) and overall survival (OS; p=0.002) were significantly decreased in these patients. High IL6 mRNA levels correlated with JAK2 amplification (p=0.008). In contrast, high Ki67 scores after NACT in TNBC residual disease did not predict RFS (p=0.42) or OS (p=0.84). Growth factor receptor amplifications were identified in EGFR, PDGFRA, PDGFRB, KIT, MET, IGF1R, FGFR1, and FGFR2 genes. ERBB2 amplifications were found in 7 patients, and these were confirmed by fluorescence in situ hybridization in both the pre- and post-treatment tissue, suggesting that NGS could assist in the identification of ERBB2-overexpressing tumors misclassified at diagnosis [Balko JM et al. \u003Cem\u003ECancer Res\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EAccording to Dr. Balko, \u201cEfforts to determine whether lesions present in the residual disease mirror those in the recurrence and whether they are selected during neoadjuvant treatment are underway.\u201d The diversity of lesions in residual TNBC after NACT highlights the need for broad molecular approaches to better inform personalized therapy in these patients [Balko JM et al. \u003Cem\u003ECancer Res\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/12\/20\/8.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzo3z1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}