Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study

Abstract

Background: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors. Patients and methods: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the KaplaneMeier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients. Results: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) ¼ 1.345, HR ¼ 1.312, and HR ¼ 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with ACtreated luminal A-like tumors. Conclusion:The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy.

Prognosis value of lymphovascular invasion in patients with invasive ductal breast carcinoma according to lymph node metastasis status

“…This is in agreement with a recent report. During the review of this manuscript, Houvenaeghel et al [ 32 ] published the results of a similar study involving more than 17,000 patients, obtaining similar results even after pairing. Interestingly, they also observed an important prognostic value even covariate with the administration of adjuvant therapy, except for Luminal A patients.…”

“…Another limitation is the stratification of patients for further analysis. While some note that the lymphovascular invasion as prognosis factor only applicable to in patients with N0 disease with tumours up to 5 cm (pT2) [ 27 ] or up to 2 cm (pT1) [ 36 ], or is modified by other risk factors [ 9 ], or have distinct prognosis factor according to the tumour subtypes [ 32 ], we face limitations due to the small number of patients included in this study. However, our global analyses are in agreement with results of also global analyses of other studies, such as from Houvenaeghel et al [ 32 ].…”

“…Another possible limitation is the type of vessel involved in this phenomenon. Even though other studies are also based on simple histology analyses of slides stained with haematoxylin and eosin [ 9 , 32 ], invasion of blood vessels has a prognostic value independent of lymphovascular invasion [ 37 ]. Although the first one is rarer than the second [ 37 , 10 ], different migration mechanisms may be involved, as mentioned above, which could help to refine the identification of patients at higher risk of distant metastases and therapeutic benefit.…”

A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©

“…Therefore, reliance upon such biomarkers to provide a reproducible and equitable surrogate biomarker to RS may be brought into question. Although measurement is not mandated for all cases of invasive breast cancer, we must acknowledge that LVI is an early indicator of metastatic dissemination [ 48 ] and has recently been reported as a significant predictor of recurrence-free (hazard ratio (HR): 1.425), disease-free (DFS) (HR: 1.345), and overall survival (OS) (HR: 1.345) outcomes in an analysis of 17,322 patients by Houvenaeghel et al [ 49 ]. Moreover, data from the aforementioned study suggests that LVI has potential to serve as a surrogate biomarker of RS predictive of patients with luminal A disease who may benefit from adjuvant chemotherapy prescription.…”

Periostin+stromal cells guide lymphovascular invasion by cancer cells

“…A critical early step in the metastatic cascade is the intravasation of cancer cells into blood and lymphatic vessels which serve as routes for cancer cells to spread to secondary sites. Lymphovascular invasion of cancer cells into lymphatic vessels is a predominant method of vascular invasion in breast cancer and is significantly associated with the presence of lymph node metastasis, development of distant metastasis, and decreased disease-free interval and overall survival (2)(3)(4)(5)(6). Despite the frequency of lymphovascular invasion in breast cancer and its association with poor clinical outcomes, the heterotypic cell interactions that drive lymphovascular invasion are not well characterized.…”