Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment

Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment | 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 Article Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment Beatrice Taurelli Salimbeni, Fabiola Giudici, Carlo Pescia, Pier Paolo Berton Giachetti, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5222884/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 10 May, 2025 Read the published version in npj Breast Cancer → Version 1 posted 11 You are reading this latest preprint version Abstract Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2-positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), significant clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood. This multicentric retrospective cohort study evaluated the prognostic significance of TILs in 110 patients with HER2+ mBC treated with pertuzumab, trastuzumab, and taxane-based chemotherapy at two Italian institutes from June 2013 to May 2024.TILs were assessed on metastatic or primary tumor samples. High TILs levels (> 5%) were independently associated with longer PFS and OS. TILs levels were higher in primary tumours than in metastases (p=0.009), with significant variation by metastatic site. These findings underscore the potential of TILs as prognostic biomarkers in HER2+ mBC, necessitating further prospective studies. Health sciences/Oncology/Cancer/Tumour biomarkers Health sciences/Biomarkers/Prognostic markers Biological sciences/Cancer/Tumour immunology HER2-positive breast cancer TILs metastatic cancer pertuzumab and trastuzumab Full Text Additional Declarations There is no conflict of interest Tables 1 to 6 are available in the Supplementary Files section. Supplementary Files Table1.pdf Table 1 Table2.pdf Table 2 Table3.pdf Table 3 Table4.pdf Table 4 Table5.pdf Table 5 Table6.pdf Table 6 Supplementaryinformation.pdf Cite Share Download PDF Status: Published Journal Publication published 10 May, 2025 Read the published version in npj Breast Cancer → Version 1 posted Editorial decision: revise 16 Dec, 2024 Review # 2 received at journal 27 Nov, 2024 Review # 3 received at journal 22 Nov, 2024 Reviewer # 3 agreed at journal 21 Nov, 2024 Review # 1 received at journal 19 Nov, 2024 Reviewer # 2 agreed at journal 18 Nov, 2024 Reviewer # 1 agreed at journal 18 Nov, 2024 Reviewers invited by journal 06 Nov, 2024 Editor assigned by journal 14 Oct, 2024 Submission checks completed at journal 14 Oct, 2024 First submitted to journal 08 Oct, 2024 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-5222884","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":374835494,"identity":"cb7083e9-029d-485a-8b1b-090203ee8cf5","order_by":0,"name":"Beatrice Taurelli 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Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), significant clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood.\r\nThis multicentric retrospective cohort study evaluated the prognostic significance of TILs in 110 patients with HER2+ mBC treated with pertuzumab, trastuzumab, and taxane-based chemotherapy at two Italian institutes from June 2013 to May 2024.TILs were assessed on metastatic or primary tumor samples. \r\nHigh TILs levels (\u003e 5%) were independently associated with longer PFS and OS. TILs levels were higher in primary tumours than in metastases (p=0.009), with significant variation by metastatic site. 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