Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab

Marco Invernizzi, Anna Michelotti, Marianna Noale, Gianluca Lopez, Letterio Runza, Massimo Giroda, Luca Despini, Concetta Blundo, Stefania Maggi, Donatella Gambini, Nicola Fusco

Research output: Contribution to journalArticle

Abstract

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 (0.4⁻25.6 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 < 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 < 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.

Original languageEnglish
Article numberE138
JournalJournal of Clinical Medicine
Volume8
Issue number2
DOIs
Publication statusPublished - Jan 24 2019

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Lymphedema
Upper Extremity
Breast Neoplasms
Neoplasms
Therapeutics
Breast Cancer Lymphedema
Trastuzumab
Taxoids
Lymph Node Excision
Proportional Hazards Models
Dissection
Radiotherapy
Neoplasm Metastasis

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Breast Cancer Systemic Treatments and Upper Limb Lymphedema : A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab. / Invernizzi, Marco; Michelotti, Anna; Noale, Marianna; Lopez, Gianluca; Runza, Letterio; Giroda, Massimo; Despini, Luca; Blundo, Concetta; Maggi, Stefania; Gambini, Donatella; Fusco, Nicola.

In: Journal of Clinical Medicine, Vol. 8, No. 2, E138 , 24.01.2019.

Research output: Contribution to journalArticle

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abstract = "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 (0.4⁻25.6 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 < 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 < 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.",
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AU - Noale, Marianna

AU - Lopez, Gianluca

AU - Runza, Letterio

AU - Giroda, Massimo

AU - Despini, Luca

AU - Blundo, Concetta

AU - Maggi, Stefania

AU - Gambini, Donatella

AU - Fusco, Nicola

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AB - 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 (0.4⁻25.6 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 < 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 < 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.

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