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This study profiles metabolic activity across distinct breast cancer subtype groups with and without doxorubicin chemotherapy, using multiple breast cell lines and Biolog phenotype mammalian microarrays to quantify metabolic output from broad substrate sets. Results show subtype-specific metabolic profiles, including enhanced glycolytic and anaerobic substrate use consistent with the Warburg effect in TNBC and metastatic cells, distinct glucose utilization and metabolic effector sensitivity in ER+/PR+ cells, and notable nucleoside and amino-acid differences between cancer and control.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/metabolic-signatures-of-breast-cancer-subtypes-and-the-metabolic-impact-of-chemotherapy/346308/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/metabolic-signatures-of-breast-cancer-subtypes-and-the-metabolic-impact-of-chemotherapy/346308.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What was the aim of the study?","Question",{"text":112,"@type":113},"To profile metabolic activity across different breast cancer subtypes, comparing patterns with and without doxorubicin chemotherapy.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were metabolic activities assessed in this research?",{"text":117,"@type":113},"Six human breast cell lines were evaluated and analyzed using Biolog phenotype mammalian microarrays (PM-M1 to PM-M8), measuring metabolic activity via NADH production across many substrate parameters.",{"name":119,"@type":110,"acceptedAnswer":120},"What key metabolic differences were observed between subtypes?",{"text":121,"@type":113},"TNBC and metastatic cells showed enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect, while ER+/PR+ cells showed heightened glucose utilization and distinct sensitivity to metabolic effectors and doxorubicin.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},346308,1790111382,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","Article  \nMetabolic Signatures of Breast Cancer Subtypes and the Metabolic Impact of Chemotherapy  \nAubrey Mattingly 1,*, Zoe Vickery 1, Alex Fiorentino 1, Ethan Wilson 1, Sydney McCune 1, Sydney Clark 1, Eric Blanchard 1, Jillian Spencer 1, Abigail Broom 2, Diana Ivankovic 2, Brooklyn Pace 2, Lauren Baskin 2, Ludovico Abenavoli 3, W. Jeffery Edenfield 4, Ki Chung 4, Christopher L. Farrell 1, Hakon Hakonarson 5 and Luigi Boccuto 1, *  \n1 Healthcare Genetics Laboratory, School of Nursing, Clemson University, Clemson, SC 29634, USA  \n2 Center for Cancer Research, Anderson University, 316 Boulevard, Anderson, SC 29621, USA  \n3 Department of Health Sciences, University “Magna Graecia”, Viale Europa-Germaneto, 88100 Catanzaro, Italy  \n4 Prisma Health Cancer Institute, Greenville, SC 29605, USA  \n5 Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA  \n* [Correspondence: mattin2@clemson.edu](Correspondence: mattin2@clemson.edu) (A.M.); [lboccut@clemson.edu](lboccut@clemson.edu) (L.B.)  \nAcademic Editor: Uwe Christians  \nReceived: 29 October 2025  \nRevised: 23 December 2025  \nAccepted: 27 December 2025  \nPublished: 8 January 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \nAbstract  \nBackground/Objectives: Breast cancer is a prevalent and heterogeneous disease with multiple subtypes, which are defined by characteristics such as molecular biomarkers and metastatic status. This study aimed to profile the metabolic activity of various breast cancer subtypes, both with and without chemotherapy (doxorubicin) application. Methods: Six human breast cell lines were evaluated, two non-tumorigenic controls and four cancerous lines. The cancer lines were clustered as primary-derived, metastasisderived, triple-negative (TNBC), and strong hormone receptor-positive (ER+/PR+) and analyzed using the Biolog phenotype mammalian microarrays (PM-M1 to PM-M8) to assess metabolic activity via NADH production under a wide array of substrate parameters. Results: Unique metabolic profiles emerged across the subtypes and clusters; the TNBC and metastatic cells demonstrated enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect. The ER+/PR+ cells showed heightened glucose utilization and unique sensitivity to metabolic effectors and doxorubicin. Additionally, significant metabolic differences were observed in nucleoside and amino acid utilization between cancer and control cells, particularly in metastatic and TNBC lines. Conclusions: Our findings reveal the profound metabolic diversity among breast cancer subtypes and highlight distinct substrate dependencies for proliferation. The results additionally provide a framework for developing metabolic biomarkers and targeted therapies for chemotherapy resistance in breast cancer subtypes.  \nKeywords: breast cancer; metabolomics; metabolic profiling; chemotherapy; metastatic; primary; triple-negative; hormone receptor-positive; therapeutic tailoring; precision medicine  \n1. Introduction  \nBreast cancer is responsible for the most cancer diagnoses and deaths in women globally; its incidence is influenced by factors such as higher hormone levels, increased age, and the presence of genetic variants, including risk factor hotspots like BRCA1 and BRCA2 variants [1] . Breast cancer can be classified based on the expression of hormone receptors and other molecular markers. Major subclassifications include hormone receptor-positive (HR+) lines, HER2-positive (HER2+) lines, and triple-negative breast cancer (TNBC) lines.  \nHR+ lines include cell lines that express estrogen receptors (ER+) and/or progesterone receptors (PR+) . HER2+ cell lines overexpress the human epidermal growth factor receptor 2, which promotes tumor growth, and TNBC lines lack ER, PR, and HER2 expression. These b","cbCaieiKjY3Srs1C","https://ap.wps.com/l/cbCaieiKjY3Srs1C","pdf",6061611,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What was the aim of the study?\",\"answer\":\"To profile metabolic activity across different breast cancer subtypes, comparing patterns with and without doxorubicin chemotherapy.\"},{\"question\":\"How were metabolic activities assessed in this research?\",\"answer\":\"Six human breast cell lines were evaluated and analyzed using Biolog phenotype mammalian microarrays (PM-M1 to PM-M8), measuring metabolic activity via NADH production across many substrate parameters.\"},{\"question\":\"What key metabolic differences were observed between subtypes?\",\"answer\":\"TNBC and metastatic cells showed enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect, while ER+/PR+ cells showed heightened glucose utilization and distinct sensitivity to metabolic effectors and doxorubicin.\"}]","Metabolic Signatures of Breast Cancer Subtypes and the Metabolic Impact of Chemotherapy | PDF",1790060858]