Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes

Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes Anna Teresa Moreira Neves, Gabriela Campos de Souza Maria, Stephanie Bruna Camilo Soares de Brito, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8935024/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Breast cancer is a heterogeneous disease with well-established prognostic factors; however, in vivo tumor growth studies are rare. This study aimed to evaluate factors associated with tumor specific growth rate (SGR), including histological grade features and the presence of tumor-infiltrating lymphocytes (TILs). Methods: We conducted a retrospective cohort study including patients whose breast lesions were either missed on imaging examinations or who experienced a delay between breast cancer diagnosis and treatment. Tumor volume was calculated in the first and last abnormal imaging examinations. New histological slides were prepared for histologic and immunohistochemical evaluation. Results: Among the 89 lesions analyzed, the mean SGR (x10-2) was 0.31 (±0.28). On multivariate analysis, factors associated with faster tumor growth were: nuclear pleomorphism score of 3 compared to scores 1 and 2 (unstandardized B = 0.198; 95% confidence interval [CI], 0.097-0.300); triple-negative subtype versus other subtypes (B = 0.187, 95% CI, 0.024-0.350); and larger tumor size at the initial examination (B = 0.010, 95% CI, 0.004-0.016). The presence of ductal carcinoma in situ (DCIS) was associated with slower tumor growth (B = -0.120, 95% CI, -0.218- 0.022). On univariate analysis, tumors with ≥ 60% of TILs showed a marginally higher SGR compared with those with associated with ≤ 10% TILs (0.44 versus 0.26, p = 0.058). Conclusions: Several established breast cancer prognostic factors were associated with SGR. Higher nuclear pleomorphism, triple‑negative subtype, and larger initial tumor size were independently associated with faster tumor growth, whereas the presence of DCIS was associated with slower growth. Higher TIL levels were marginally associated with increased SGR, suggesting a potential role in breast cancer growth dynamics. breast cancer natural history diagnostic errors Breast carcinoma in situ neoplasm grading Figures Figure 1 Figure 2 Full Text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8935024","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":598920311,"identity":"1bc59b41-b91b-4296-a52d-f9079af350fe","order_by":0,"name":"Anna Teresa Moreira Neves","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"Teresa Moreira","lastName":"Neves","suffix":""},{"id":598920312,"identity":"2f3f5105-58d6-4813-89b9-4a53f779859c","order_by":1,"name":"Gabriela Campos de Souza Maria","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Gabriela","middleName":"Campos de Souza","lastName":"Maria","suffix":""},{"id":598920313,"identity":"8e754b1e-b43f-47d0-bf6f-fda778077a83","order_by":2,"name":"Stephanie Bruna Camilo Soares de Brito","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"Bruna Camilo Soares","lastName":"de Brito","suffix":""},{"id":598920314,"identity":"c7ddade9-d06c-4c92-a3e5-a43b86c6cbbe","order_by":3,"name":"Renato Camata Couto","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Renato","middleName":"Camata","lastName":"Couto","suffix":""},{"id":598920315,"identity":"b94bd832-161b-4a85-b27a-5d764ad32a54","order_by":4,"name":"Thais Abreu de Castro","email":"","orcid":"","institution":"Radiocentro Diagnóstico por Imagem","correspondingAuthor":false,"prefix":"","firstName":"Thais","middleName":"Abreu","lastName":"de Castro","suffix":""},{"id":598920316,"identity":"627425d2-46a0-42a2-b55b-6dbbef315d16","order_by":5,"name":"Pedro Lobo Alcantara Neves","email":"","orcid":"","institution":"Laboratório Hermes Pardini: Instituto Hermes Pardini SA","correspondingAuthor":false,"prefix":"","firstName":"Pedro","middleName":"Lobo Alcantara","lastName":"Neves","suffix":""},{"id":598920317,"identity":"fc367da7-78cd-4e35-bd23-2437c56fc5ba","order_by":6,"name":"Mauro Nogueira Cardoso","email":"","orcid":"","institution":"Pontifícia Universidade Católica de Minas Gerais: Pontificia Universidade Catolica de Minas Gerais: Coletivo da Saúde","correspondingAuthor":false,"prefix":"","firstName":"Mauro","middleName":"Nogueira","lastName":"Cardoso","suffix":""},{"id":598920318,"identity":"4bb8c290-6670-41b3-8886-1a3bea0df94d","order_by":7,"name":"Amanda Alves Assunção","email":"","orcid":"","institution":"Centro Especializado em Histotecnologia","correspondingAuthor":false,"prefix":"","firstName":"Amanda","middleName":"Alves","lastName":"Assunção","suffix":""},{"id":598920319,"identity":"df126efd-abda-453c-8196-5c57a5aba01b","order_by":8,"name":"Cristiana Buzelin Nunes","email":"","orcid":"","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Cristiana","middleName":"Buzelin","lastName":"Nunes","suffix":""},{"id":598920320,"identity":"497ebde1-06a6-43bb-bafe-5f263edf6b5b","order_by":9,"name":"Débora Balabram","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDCCAzwMDA8YDjAwsDcAeQYWRGpJAGnhOQDSIkGKFokEEJcILXzHew9+SKi5k88/8/nVDT8KJBj427sT8GqRPHMuWSLh2DPLGbdzym72AB0mcebsBrxaDG7kGEgksB02YLidk3aDB6jFQCKXgJb7b4x/JPw7bCB/80zazT9EabnBYyaR2HbYwOAG+7HbRNkieSYvzSKx75mB4ZkcttsyBhI8BP3Cd/zs4Rsfvt0xkDt+/NnNN39s5Pjbe/FrQQI8BmCSWOUgwP6AFNWjYBSMglEwggAA8ChRB3TtmMYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-3077-7526","institution":"Universidade Federal de Minas Gerais Faculdade de Medicina","correspondingAuthor":true,"prefix":"","firstName":"Débora","middleName":"","lastName":"Balabram","suffix":""}],"badges":[],"createdAt":"2026-02-21 17:47:54","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8935024/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8935024/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104181058,"identity":"4220f8b6-0532-4d32-9ea6-a3db0b19f28f","added_by":"auto","created_at":"2026-03-08 17:24:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3398029,"visible":true,"origin":"","legend":"\u003cp\u003ea and b, Mammograms of a patient with triple-negative breast cancer in the\u003cbr\u003e\nleft breast on different dates. Specific growth rate (x10-2): 1.02. This lesion was initially\u003cbr\u003e\nconsidered benign. The interval between a and b was 3 months. c and d, Mammograms\u003cbr\u003e\nof a patient with luminal B-like breast cancer in the left breast. Specific growth rate (x10-\u003cbr\u003e\n2): 0,21. The interval between c and d was 20 months.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8935024/v1/942623384bca50406cdd9fa9.png"},{"id":104180940,"identity":"1e3baffc-33cb-41b5-9b7f-9e6ebfd4ba27","added_by":"auto","created_at":"2026-03-08 17:24:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":105801,"visible":true,"origin":"","legend":"\u003cp\u003eBoxplot showing features associated with tumor-specific growth rate in 89\u003cbr\u003e\nbreast cancers assessed on more than one imaging examination. P values refer to\u003cbr\u003e\nANOVA. (a) Mitotic count (p \u0026lt; 0.001). (b) Nuclear pleomorphism (p \u0026lt; 0.001). (c) Tubule\u003cbr\u003e\nand gland formation (p = 0.012). (d) Presence of ductal carcinoma in situ (p = 0.021). (e)\u003cbr\u003e\nImmunohistochemical tumor subtype (p \u0026lt; 0.001). (f) Tumor infiltrating lymphocytes (p =\u003cbr\u003e\n0.058).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8935024/v1/1e6cbfd978b04e6eecdd1ea5.png"},{"id":106094258,"identity":"95b63db0-4087-4c55-904a-88a77ea28024","added_by":"auto","created_at":"2026-04-03 11:41:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":933950,"visible":true,"origin":"","legend":"","description":"","filename":"SGRfeb2026BC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8935024/v1_covered_c2f00e8d-3678-497e-9d8b-bc0f93a2258b.pdf"}],"financialInterests":"","formattedTitle":"Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast cancer, natural history, diagnostic errors, Breast carcinoma in situ, neoplasm grading","lastPublishedDoi":"10.21203/rs.3.rs-8935024/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8935024/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Purpose: Breast cancer is a heterogeneous disease with well-established prognostic factors; however, in vivo tumor growth studies are rare. This study aimed to evaluate factors associated with tumor specific growth rate (SGR), including histological grade features and the presence of tumor-infiltrating lymphocytes (TILs). Methods: We conducted a retrospective cohort study including patients whose breast lesions were either missed on imaging examinations or who experienced a delay between breast cancer diagnosis and treatment. Tumor volume was calculated in the first and last abnormal imaging examinations. New histological slides were prepared for histologic and immunohistochemical evaluation. Results: Among the 89 lesions analyzed, the mean SGR (x10-2) was 0.31 (±0.28). On multivariate analysis, factors associated with faster tumor growth were: nuclear pleomorphism score of 3 compared to scores 1 and 2 (unstandardized B = 0.198; 95% confidence interval [CI], 0.097-0.300); triple-negative subtype versus other subtypes (B = 0.187, 95% CI, 0.024-0.350); and larger tumor size at the initial examination (B = 0.010, 95% CI, 0.004-0.016). The presence of ductal carcinoma in situ (DCIS) was associated with slower tumor growth (B = -0.120, 95% CI, -0.218- 0.022). On univariate analysis, tumors with ≥ 60% of TILs showed a marginally higher SGR compared with those with associated with ≤ 10% TILs (0.44 versus 0.26, p = 0.058). Conclusions: Several established breast cancer prognostic factors were associated with SGR. Higher nuclear pleomorphism, triple‑negative subtype, and larger initial tumor size were independently associated with faster tumor growth, whereas the presence of DCIS was associated with slower growth. Higher TIL levels were marginally associated with increased SGR, suggesting a potential role in breast cancer growth dynamics.","manuscriptTitle":"Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-08 17:23:28","doi":"10.21203/rs.3.rs-8935024/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5e7ae3ef-945a-4f12-9e55-e09b48452caf","owner":[],"postedDate":"March 8th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-02T09:59:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-08 17:23:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8935024","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8935024","identity":"rs-8935024","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}