Prone Sites of Brain Metastases in Breast Cancer: A Voxel-wise Analysis Based on Clinical Features

Prone Sites of Brain Metastases in Breast Cancer: A Voxel-wise Analysis Based on Clinical Features | 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 Prone Sites of Brain Metastases in Breast Cancer: A Voxel-wise Analysis Based on Clinical Features Hairong Wang, Hongyu Chen, Haoqun Xie, Hao Duan, Lei Lin, Jiangen Chen, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6670187/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Purpose Brain metastases (BMs) occur in 15–30% of breast cancer patients, particularly in HER2-positive and triple-negative subtypes, and signify poor prognosis. This study aimed to identify vulnerable BM locations through voxel-wise analysis of clinical characteristics. Method We retrospectively analyzed 161 breast cancer patients with BMs (2007–2019) and performed voxel-wise MRI analysis using standardized templates. Segmentation results were superimposed on standard brain templates to construct stereo-specific frequency thermograms and compared under the same voxel. Two-tailed Fisher's exact test was performed. Overall survival (OS) and post-progression survival (PPS) after confirmation of brain metastases were tested by Kaplan-Meier, Cox regression analysis calculation, and log-rank test. Result The frequency heat map shows lesions of patients with breast cancer brain metastases were more inclined to the cerebellar hemisphere. Older patients’ lesions mainly occurred in the right frontal lobe, the left parietal lobe, and adjacent meninges compared with white matter of the right parietal lobe and cerebellar vermis among younger patients. ER-positive and PR-positive and HER2-overexpressed patients presented significance in the parieto-occipital lobe, cerebellum and adjacent meninges. Metastases with high levels of CEA were found in areas around the central anterior gyrus. HER2-overexpressed in primary sites and a normal level of serum CA15-3 were two independent protective factors in determining prognostic outcomes. Conclusion The preferred locations of breast cancer with brain metastases could be observed based on different clinical and biological characteristics, which could be clues for further study and helpful for clinical strategies. Breast cancer Brain metastases Clinical characteristics Panoramic view Full Text Additional Declarations No competing interests reported. Supplementary Files supplementaryfiles.zip Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 21 Jul, 2025 Reviews received at journal 07 Jul, 2025 Reviews received at journal 07 Jul, 2025 Reviews received at journal 07 Jul, 2025 Reviews received at journal 03 Jul, 2025 Reviews received at journal 19 Jun, 2025 Reviewers agreed at journal 19 Jun, 2025 Reviewers agreed at journal 18 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers agreed at journal 16 Jun, 2025 Reviewers agreed at journal 13 Jun, 2025 Reviewers invited by journal 13 Jun, 2025 Editor assigned by journal 13 Jun, 2025 Editor invited by journal 05 Jun, 2025 Submission checks completed at journal 04 Jun, 2025 First submitted to journal 04 Jun, 2025 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. 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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-6670187","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":472114408,"identity":"08e89c4e-b1b5-4639-a0f6-88b8738e5297","order_by":0,"name":"Hairong Wang","email":"","orcid":"","institution":"Sun Yat-sen University Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Hairong","middleName":"","lastName":"Wang","suffix":""},{"id":472114409,"identity":"6858ac36-ec0b-47c0-8bfd-317a7cd729e7","order_by":1,"name":"Hongyu Chen","email":"","orcid":"","institution":"Sun Yat-sen University Cancer 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Clinical characteristics, Panoramic view","lastPublishedDoi":"10.21203/rs.3.rs-6670187/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6670187/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eBrain metastases (BMs) occur in 15\u0026ndash;30% of breast cancer patients, particularly in HER2-positive and triple-negative subtypes, and signify poor prognosis. This study aimed to identify vulnerable BM locations through voxel-wise analysis of clinical characteristics.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 161 breast cancer patients with BMs (2007\u0026ndash;2019) and performed voxel-wise MRI analysis using standardized templates. Segmentation results were superimposed on standard brain templates to construct stereo-specific frequency thermograms and compared under the same voxel. Two-tailed Fisher's exact test was performed. Overall survival (OS) and post-progression survival (PPS) after confirmation of brain metastases were tested by Kaplan-Meier, Cox regression analysis calculation, and log-rank test.\u003c/p\u003e\u003ch2\u003eResult\u003c/h2\u003e \u003cp\u003eThe frequency heat map shows lesions of patients with breast cancer brain metastases were more inclined to the cerebellar hemisphere. Older patients\u0026rsquo; lesions mainly occurred in the right frontal lobe, the left parietal lobe, and adjacent meninges compared with white matter of the right parietal lobe and cerebellar vermis among younger patients. ER-positive and PR-positive and HER2-overexpressed patients presented significance in the parieto-occipital lobe, cerebellum and adjacent meninges. Metastases with high levels of CEA were found in areas around the central anterior gyrus. HER2-overexpressed in primary sites and a normal level of serum CA15-3 were two independent protective factors in determining prognostic outcomes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe preferred locations of breast cancer with brain metastases could be observed based on different clinical and biological characteristics, which could be clues for further study and helpful for clinical strategies.\u003c/p\u003e","manuscriptTitle":"Prone Sites of Brain Metastases in Breast Cancer: A Voxel-wise Analysis Based on Clinical Features","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 14:58:25","doi":"10.21203/rs.3.rs-6670187/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-21T09:51:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-07T19:58:03+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-07T18:04:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-07T11:43:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-03T13:44:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-06-19T07:38:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282849082134265341441218982895906631184","date":"2025-06-19T06:38:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"263829415664952833468387944100027799630","date":"2025-06-18T19:42:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246314625120501809762639417827094848501","date":"2025-06-16T16:23:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264141403682974327650028556161268508829","date":"2025-06-16T08:02:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"133214922190106524834776522555180198911","date":"2025-06-13T16:06:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-13T14:59:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-13T14:48:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-05T13:23:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-04T16:01:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-06-04T15:57:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"58671468-d129-43ac-9b30-91a6fa50ce67","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-06T17:23:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 14:58:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6670187","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6670187","identity":"rs-6670187","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}