Lymphovascular invasion and extranodal tumor extension as risk indicators of breast cancer-related lymphedema.

e12609 Background: Breast cancer related lymphedema (BCRL) occurs in up to 54% of breast cancer (BC) patients after radiotherapy and/or surgery. This condition is a major contributor to women disability. To date, there are no validated predictive biomarkers, diagnostic tools, and curative treatments supported by strong evidence for these patients, which make BCRL an issue to be urgently addressed. Here, we provide an integrative characterization of a large series of women with node-positive (N+) BC and identified new bona fide predictors of BCRL occurrence. Methods: 332 surgically-treated N+ BCs were retrospectively collected (2-19 years of follow-up). Among them, 62 BCRL patients and 270 BCRL-negative patients were clustered in the study group and control group, respectively. To identify demographic and clinicopathologic features related to BCRL, Fisher's exact test or Chi-squared test were carried out for categorical variables, while the Wilcoxon rank-sum was employed for continuous variables. Factors associated with a hazard ratio of developing BCRL were assessed using a Cox proportional hazard regression model. Results: En-bloc dissection of the axillary lymph nodes but not the type breast surgery impacted on BCRL development. Most of BCRL patients had a Luminal A-like neoplasm and concurrent obesity, dyslipidemia, and/or chronic infections. The number of lymph nodes involved by metastatic deposits was significantly higher in BCRL compared to the control group. Both peritumoral lymphovascular invasion (LVI) and extranodal extension (ENE) of the metastasis had a negative impact on BCRL-free survival, particularly when considering the laterality of surgery. Patients with LVI and left side localization harbored 4-fold higher risk of BCRL. Right-arm metastases with ENE in patients subjected to axillary dissection increased the probability to develop BCRL compared to ENE-negative patients. Conclusions: The routinary evaluation of LVI and ENE either on pre-surgical (e.g. core biopsies), intra-surgical (e.g. intraoperative sentinel lymph nodes), or post-surgical (e.g. breast and axillary nodes excision) samples might represent the basis for a novel strategy in BCRL risk stratification.