The Role of Lymph Node Metastasis in the Systemic Dissemination of Breast Cancer

Abstract

Background. Lymphatic invasion is necessary for regional lymph node (RLN) metastasis in breast cancer (BC), while systemic metastasis requires blood vessel (BV) invasion. The site of BV invasion could be at the primary BC site or through lymphovascular anastomoses. The vague pathologic term ''lymphovascular invasion'' (LVI) encourages the belief that peri/intratumoral BV invasion may be common. We investigated the relative contribution of RLN metastasis to systemic metastasis by studying the relationship among LVI and RLN and/or systemic metastasis in a population-based cohort of breast cancer patients. Methods. Fisher's exact test was done to assess global associations among LVI and RLN and/or systemic metastasis in a prospective database of breast cancer patients undergoing RLN biopsy. Logistic regression was used to determine multivariable contributions of LVI to metastasis when controlling for available demographic, radiologic, and pathologic variables. Results. Of 1668 patients evaluated 25.4% were RLN positive and 10.4% had LVI. RLN metastasis was predicted by tumor size (P \ .0001), HER-2/neu overexpression (P = .0022) and the interaction between LVI positive and HER-2/neu positive tumors (\ .0001). Patients with LVI/ HER-2-neu positive were 3 times as likely to have positive RLNs compared with patients LVI/HER-2-neu negative.Systemic metastasis was significantly (P = .0013) associated with LVI/ RLN positive, but not with LVI positive/ RLN negative patients (P = .137). Conclusions. LVI predicted RLN metastasis. LVI also significantly predicted systemic metastasis, but only when the RLN was also positive. Since RLN requires lymphatic invasion, these data support the hypothesis that primary breast cancers often invade lymphatics to gain access to the systemic circulation.The systemic metastasis cascade, a concept theorized, confirmed at autopsy by pathologists, clinically and in animal models, and studied in numerous laboratory experiments, suggests that tumor-induced angiogenesis promotes systemic breast cancer (BC) metastases because of direct peritumoral and/or intratumoral invasion of tumor cells into blood vessel capillaries (BVCs).

Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis

“…We believe that the approach described here is highly relevant not only to metastatic breast cancer but also to a number of adenocarcinomas, in which miR-10b plays a role. 17 On a broader scale, the delivery strategy illustrated by our studies could provide a useful research tool for the elucidation of context-dependent differences in miRNA function and the translation of this knowledge to a clinical setting.…”

High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

“…Due to lack of the specific markers of lymphatic endothelium cells, most of the previous studies have detected lymphovascular invasion using H&E staining method [11, 12]. One major challenge of this method is to distinguish lymphovascular invasion from retraction artifacts caused by tissue handling and fixation on H&E stained sections.…”

“…Lymphovascular invasion, infiltration of tumor cells into lymphatic vessels, represents a high invasion feature of breast tumor cells. Determined by hematoxylin and eosin (H&E) staining in past time, lymphovascular invasion was widely investigated and showed a correlation with the clinicopathological outcomes of breast cancer [11, 12]. At present, lymphatic vessels can be distinguished from blood vessels or retraction artifacts.…”

The relationship of lymphatic vessel density, lymphovascular invasion, and lymph node metastasis in breast cancer: a systematic review and meta-analysis

“…The detection of LVI was mainly assessed by H&E staining method, due to the deficiency of specific markers of lymphatic vessels [46, 47]. One major challenge of this method is to distinguish LVI from the retraction artifacts caused by tissue handling and fixation.…”