Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: An observational retrospective study with long-term follow-up 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

M. Invernizzi, C. Corti, G. Lopez, A. Michelotti, L. Despini, D. Gambini, D. Lorenzini, E. Guerini-Rocco, S. Maggi, M. Noale, N. Fusco

Research output: Contribution to journalArticle

Abstract

Background: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. Methods: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. Conclusions: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification. © 2018 The Author(s).
Original languageEnglish
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - 2018

Fingerprint

Observational Studies
Carcinogenesis
Retrospective Studies
Health
Neoplasms
Breast Neoplasms
Breast Cancer Lymphedema
Neoplasm Metastasis
Lymph Node Excision
Proportional Hazards Models
Survivors
Breast
Biomarkers
Lymph Nodes
Demography
Control Groups
Survival

Keywords

  • Axillary lymph nodes dissection
  • Breast cancer
  • Breast cancer related lymphoedema
  • Extracapsular extension
  • Lymphovascular invasion
  • adult
  • aged
  • Article
  • axillary lymph node
  • breast cancer-related lymphedema
  • breast surgery
  • cancer localization
  • cancer risk
  • cancer staging
  • cancer survival
  • clinical assessment
  • clinical feature
  • clinical protocol
  • controlled study
  • disease association
  • disease free survival
  • extranodal tumor extension
  • female
  • follow up
  • histopathology
  • human
  • human tissue
  • long term care
  • lymph node dissection
  • lymph vessel metastasis
  • major clinical study
  • metastasis
  • observational study
  • prevalence
  • retrospective study
  • axilla
  • lymph node
  • middle aged
  • mortality
  • pathology
  • tumor invasion
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Axilla
  • Breast Cancer Lymphedema
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Lymph Node Excision
  • Lymph Nodes
  • Middle Aged
  • Neoplasm Invasiveness
  • Retrospective Studies

Cite this

@article{2798a5b9af4a4a7ab028b064698a9b28,
title = "Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: An observational retrospective study with long-term follow-up 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis",
abstract = "Background: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. Methods: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. Conclusions: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification. {\circledC} 2018 The Author(s).",
keywords = "Axillary lymph nodes dissection, Breast cancer, Breast cancer related lymphoedema, Extracapsular extension, Lymphovascular invasion, adult, aged, Article, axillary lymph node, breast cancer-related lymphedema, breast surgery, cancer localization, cancer risk, cancer staging, cancer survival, clinical assessment, clinical feature, clinical protocol, controlled study, disease association, disease free survival, extranodal tumor extension, female, follow up, histopathology, human, human tissue, long term care, lymph node dissection, lymph vessel metastasis, major clinical study, metastasis, observational study, prevalence, retrospective study, axilla, lymph node, middle aged, mortality, pathology, tumor invasion, very elderly, Adult, Aged, Aged, 80 and over, Axilla, Breast Cancer Lymphedema, Disease-Free Survival, Female, Follow-Up Studies, Humans, Lymph Node Excision, Lymph Nodes, Middle Aged, Neoplasm Invasiveness, Retrospective Studies",
author = "M. Invernizzi and C. Corti and G. Lopez and A. Michelotti and L. Despini and D. Gambini and D. Lorenzini and E. Guerini-Rocco and S. Maggi and M. Noale and N. Fusco",
note = "Cited By :1 Export Date: 5 February 2019 CODEN: BCMAC Correspondence Address: Fusco, N.; Division of Pathology, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Italy; email: nicola.fusco@unimi.it Funding text 1: M.I. is funded in part by the Edo and Elvo Tempia Foundation, Biella, Italy. G.L. is funded by an OXIAMO Onlus Post-Graduate Fellowship. 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year = "2018",
doi = "10.1186/s12885-018-4851-2",
language = "English",
volume = "18",
journal = "BMC Cancer",
issn = "1471-2407",
publisher = "BioMed Central Ltd.",
number = "1",

}

TY - JOUR

T1 - Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: An observational retrospective study with long-term follow-up 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis

AU - Invernizzi, M.

AU - Corti, C.

AU - Lopez, G.

AU - Michelotti, A.

AU - Despini, L.

AU - Gambini, D.

AU - Lorenzini, D.

AU - Guerini-Rocco, E.

AU - Maggi, S.

AU - Noale, M.

AU - Fusco, N.

N1 - Cited By :1 Export Date: 5 February 2019 CODEN: BCMAC Correspondence Address: Fusco, N.; Division of Pathology, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, Italy; email: nicola.fusco@unimi.it Funding text 1: M.I. is funded in part by the Edo and Elvo Tempia Foundation, Biella, Italy. G.L. is funded by an OXIAMO Onlus Post-Graduate Fellowship. References: Asdourian, M.S., Skolny, M.N., Brunelle, C., Seward, C.E., Salama, L., Taghian, A.G., Precautions for breast cancer-related lymphoedema: Risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis (2016) Lancet Oncol, 17, pp. e392-e405; Shaitelman, S.F., Chiang, Y.J., Griffin, K.D., Desnyder, S.M., Smith, B.D., Schaverien, M.V., Woodward, W.A., Cormier, J.N., Radiation therapy targets and the risk of breast cancer-related lymphedema: A systematic review and network meta-analysis (2017) Breast Cancer Res Treat, 162, pp. 201-215. , 1:CAS:528:DC%2BC28XitFGitL3F; Coriddi, M., Khansa, I., Stephens, J., Miller, M., Boehmler, J., Tiwari, P., Analysis of factors contributing to severity of breast cancer-related lymphedema (2015) Ann Plast Surg, 74, pp. 22-25. , 1:CAS:528:DC%2BC2cXitVOhsLbF; Specht, M.C., Miller, C.L., Russell, T.A., Horick, N., Skolny, M.N., O'Toole, J.A., Jammallo, L.S., Shenouda, M.N., Defining a threshold for intervention in breast cancer-related lymphedema: What level of arm volume increase predicts progression? 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PY - 2018

Y1 - 2018

N2 - Background: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. Methods: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. Conclusions: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification. © 2018 The Author(s).

AB - Background: Breast cancer related lymphoedema (BCRL) occurs in a substantial proportion of breast cancer survivors and is a major contributor to patients' disability. Regrettably, there are no validated predictive biomarkers, diagnostic tools, and strong evidence-supported therapeutic strategies for BCRL. Here, we provide an integrative characterization of a large series of women with node-positive breast cancers and identify new bona fide predictors of BCRL occurrence. Methods: Three hundred thirty-two cases of surgically-treated node-positive breast cancers were retrospectively collected (2-10.2 years of follow-up). Among them, 62 patients developed BCRL. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables; the Wilcoxon rank-sum was employed for continuous variables. Factors associated with BCRL occurrence were assessed using a Cox proportional hazards regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type of breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm. The median number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group (p = 0.04). Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival (p = 0.01). Specifically, patients with LVI and left side localization harboured 4-fold higher risk of developing BCRL, while right axillary nodes metastases with ENE increased the probability of BCRL compared to ENE-negative patients. Conclusions: Assessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification. © 2018 The Author(s).

KW - Axillary lymph nodes dissection

KW - Breast cancer

KW - Breast cancer related lymphoedema

KW - Extracapsular extension

KW - Lymphovascular invasion

KW - adult

KW - aged

KW - Article

KW - axillary lymph node

KW - breast cancer-related lymphedema

KW - breast surgery

KW - cancer localization

KW - cancer risk

KW - cancer staging

KW - cancer survival

KW - clinical assessment

KW - clinical feature

KW - clinical protocol

KW - controlled study

KW - disease association

KW - disease free survival

KW - extranodal tumor extension

KW - female

KW - follow up

KW - histopathology

KW - human

KW - human tissue

KW - long term care

KW - lymph node dissection

KW - lymph vessel metastasis

KW - major clinical study

KW - metastasis

KW - observational study

KW - prevalence

KW - retrospective study

KW - axilla

KW - lymph node

KW - middle aged

KW - mortality

KW - pathology

KW - tumor invasion

KW - very elderly

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Axilla

KW - Breast Cancer Lymphedema

KW - Disease-Free Survival

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Lymph Node Excision

KW - Lymph Nodes

KW - Middle Aged

KW - Neoplasm Invasiveness

KW - Retrospective Studies

U2 - 10.1186/s12885-018-4851-2

DO - 10.1186/s12885-018-4851-2

M3 - Article

VL - 18

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

ER -