Lymphovascular invasion and extranodal tumour extension are risk indicators of breast cancer related lymphoedema: an observational retrospective study with long-term follow-up

Abstract

BackgroundBreast 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.MethodsThree 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.ResultsEn-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.ConclusionsAssessment of LVI and ENE should be integrated with clinical and surgical data to improve BCRL risk stratification.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4851-2) contains supplementary material, which is available to authorized users.

A Novel Multimodal Radiomics Model for Preoperative Prediction of Lymphovascular Invasion in Rectal Cancer

“…There have been no studies on lymphovascular invasion of rectal cancer using radiomics. Lymphovascular invasion has been studied in breast (28); colorectal (29); and endometrial cancers (30); and urinary tract urothelial carcinoma (31). However, radiomics was only used in the lymphovascular invasion of breast cancer (32).…”

PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer

“…The Shapiro-Wilk test was used to analyze the normal distributions of continuous variables [55]. Relationships between MMR status, PTEN expression, and the characteristics of the patient population (i.e., demographic and clinical traits, data on treatment, pathological, and molecular features) were assessed using Fisher's exact test or Chi-squared test (categorical variables), and Wilcoxon rank-sum test (continuous variables) [56]. To identify factors associated with MMR deficiency, multinomial logistic regression models were defined considering a stepwise selection procedure (p-value to entry 0.25; p-value to stay 0.20).…”

Integrating Biological Advances Into the Clinical Management of Breast Cancer Related Lymphedema

“…The physical disruption of the arm lymphatics, such as in case of axillary lymph node dissection (ALND), is a well-established determinant of BCRL (55). Of note, both the number of lymph nodes removed and the number of metastatic lymph nodes are associated with an increased risk (56,57). It has been hypothesized that this could be due to the higher dose of radiations that these patients receive in the axilla (55,57).…”

“…Of note, both the number of lymph nodes removed and the number of metastatic lymph nodes are associated with an increased risk (56,57). It has been hypothesized that this could be due to the higher dose of radiations that these patients receive in the axilla (55,57). Hence, radiation-induced necrosis is likely to be involved BCRL pathogenesis (58).…”

“…The correlation between body max index (BMI) >25 kg/m 2 , post-operative weight increase, dyslipidemia, and BCRL has been widely demonstrated (8). However, novel tumor-specific pathological features, such as peritumoral lymphovascular invasion and the extra-nodal extension of the metastatic deposits, have recently been proposed to improve BCRL risk stratification (56,57). In general, there is a wide agreement that breast-conserving surgery is protective against long-term complications, including BCRL (62).…”