{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:58:43Z","timestamp":1792673923098,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Breast cancer related lymphedema (BCRL) is frequent but strategies for an individualized risk assessment are lacking. We aimed to define whether tumor-specific pathological features, coupled with clinical and therapeutic data, could help identify patients at risk. Data from 368 patients with node-positive breast cancers were retrospectively collected, including 75 patients with BCRL (0.4\u201325.6 years follow-up). BCRL was assessed during the standard follow-up oncology visits using the circumferential measurement. Clinicopathologic and therapeutic factors associated with BCRL were integrated into a Cox proportional hazards regression model. Lymphovascular invasion (LVI) was more common in BCRL patients (n = 33, 44% vs. n = 85, 29%, p = 0.01), akin extra nodal extension (ENE) of the metastasis (n = 57, 76% vs. n = 180, 61%, p = 0.02). Sentinel lymph node excision without axillary dissection and extra-axillary radiotherapy were BCRL-unrelated. A higher number of BCRL-positive patients were treated with taxane-based chemotherapy with or without trastuzumab, compared to BCRL-negative patients (p &lt; 0.01). Treatment with trastuzumab and\/or taxanes, adjusted for systemic infections, laterality, therapy, and pathological features (i.e., LVI and ENE), had a significant impact in BCRL-free survival (p &lt; 0.01). This work offers new insights on BCRL risk stratification, where the integration of clinical, therapeutic, and tumor-specific pathological data suggests a possible role of anti-human epidermal growth factor receptor 2 (HER2) therapy in BCRL pathogenesis.<\/jats:p>","DOI":"10.3390\/jcm8020138","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T11:12:48Z","timestamp":1548328368000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5141-0681","authenticated-orcid":false,"given":"Marco","family":"Invernizzi","sequence":"first","affiliation":[{"name":"Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont \u201cA. Avogadro\u201d, Viale Piazza D\u2019Armi 1, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Michelotti","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Division of Medical Oncology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-139X","authenticated-orcid":false,"given":"Marianna","family":"Noale","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Neuroscience Institute Aging Branch, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Lopez","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"School of Pathology, University of Milan, Via Festa del Perdono 7, 20122 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Letterio","family":"Runza","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Giroda","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Despini","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Blundo","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0453-8663","authenticated-orcid":false,"given":"Stefania","family":"Maggi","sequence":"additional","affiliation":[{"name":"National Research Council (CNR), Neuroscience Institute Aging Branch, Via Giustiniani 2, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Gambini","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-9131","authenticated-orcid":false,"given":"Nicola","family":"Fusco","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Della Commenda 10, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/cge.12381","article-title":"Personalized therapy for breast cancer","volume":"86","author":"Schwartz","year":"2014","journal-title":"Clin. 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