Clinicopathological characteristics that predict the prognostic risk of cancer are responsible for the improved survival results that breast cancer patients experience under the present therapy paradigm. Through effective targeting, clinicians are provided with appropriate therapeutic approaches for patients with breast cancer in various risk groups. Precision medicine is now the standard of care for breast cancer patients, and creating effective treatment regimens requires accurate risk classification of the illness. Conventional prognostic risk indicators, like TNM staging and histological grading, are well known and used in reputable prognostic evaluation systems for breast cancer, like the AJCC[13]. However, these factors did not show high prognostic value in specific categories of breast cancer. This suggests that current staging systems are still insufficient to accurately predict prognosis and accurately reflect the biological heterogeneity of breast cancer[14, 15].
The essential condition for the systematic spread of breast cancer cells to other regions is that they must first penetrate and spread throughout the lymphovascular system[16]. Tumor cells in the endothelial lining space of lymphatic vessels or blood vessels surrounding the primary tumor might enter adjacent lymphatic vessels or blood vessels and bind to one another, forming a tumor embolism known as LVI[17]. The College of American Pathologists recommends assessing and reporting LVI in all cancer protocols, which is the gold standard for cancer reporting[18]. Though its predictive utility in breast cancer is still debatable, LVI certainly plays a role in treatment selection for breast cancer. For patients with LVI, the St. Gallen International Consensus Guidelines recommend whole-breast irradiation as opposed to localized irradiation[19]. According to recent investigations, the 21-gene recurrence score can be reliably determined by detecting LVI[20]. Consequently, knowing how LVI affects breast cancer patient survival and the progression of the disease may lead to new therapeutic and diagnostic approaches that will enhance the prognosis of breast cancer patients.
In this study, we collected data from approximately two thousand invasive breast cancer patients who had therapy at our medical center during the previous nine years. Consistent with earlier studies[21], statistical analysis revealed that LVI was linked to detrimental clinicopathological characteristics, such as T stage, N stage, and neurological invasion. Tumor size and lymph node metastasis of breast cancer are intuitive bases for predicting cancer recurrence and metastasis, both of which are closely related to the degree of differentiation of the tumor cells and the invasive ability of the cancer. Our study's findings indicate that even in the absence of lymph node metastases, breast cancer patients with LVI are at risk for recurrence, so it's important to evaluate carefully whether postoperative adjuvant radiation therapy should be used in these cases following the recommended course of treatment for lymph node metastases.
Key indicators for evaluating the prognosis of patients are the overall and disease-free survival rates for breast cancer. In our study, breast cancer patients with LVI had worse OS and DFS prognosis. LVI predicts a poor prognosis in all subtypes of breast cancer, except luminal A. LVI, T stage, N stage, and menstrual status were independent predictive biomarkers of poor OS and DFS in patients with invasive breast cancer, according to survival analysis. Our research indicates that, when it comes to determining the predictive risk of breast cancer, LVI is not less useful than conventional clinicopathological factors such as tumor size and lymph node metastatic status. As a result, when formulating treatment plans, physicians shouldn't ignore the prognostic significance of LVI in breast cancer. In the meanwhile, patients having LVI for breast cancer may have an increased chance of developing recurring metastases. These individuals ought to be categorized as having a medium or high risk of developing new cancer metastases, and they ought to be the target of appropriate adjuvant therapy plans.
Malignant tumor cells extrude the junction of lymphatic endothelial cells (LEC) and move along the LEC to the subsequent stop lymph nodes and organs during lymphatic metastasis of breast cancer[9]. Tumor cells use LEC to facilitate malignancy invasion within the tumor microenvironment[22]. Kahn et al.[23] identified the monoclonal antibody D2-40 as a lymphatic vessel endothelial marker in 2002. When it comes to assessing lymphatic vessel invasion, D2-40 outperforms H&E staining in two ways: first, it can identify tumor emboli that are obstructing the lymphatic vessel lumen; second, it can distinguish between tumor aggregates because of tissue contraction during fixation and retraction artifacts that separate tumor emboli in the lymphatic vessel space. D2-40 enhanced the detection of lymphatic vessel invasion in primary tumors, according to Kahn's study. M. Debald et al.[24] recommended routine D2-40 immunohistochemical staining to improve recognition of lymphatic vessel invasion. In this study, we used D2-40 immunohistochemical staining to mark breast cancer tissue showing LVI under H&E staining. According to the findings, patients with positive D2-40 staining predicted a higher risk of N-stage and localized recurrence of the tumor. Since positive D2-40 staining suggests the presence of lymphatic vessel invasion, it is reasonable to assume that lymphatic vessel invasion, rather than blood vessel invasion (BVI), is a relevant risk factor for promoting lymph node metastasis and localized recurrence of breast cancer. This offers novel perspectives on how lymphatic vessel invasion affects the progression of breast cancer development. Therefore, we believe that D2-40 could be added to the diagnostic procedures for breast cancer LVI as a complement to H&E staining.
Tumor-associated angiogenesis is one of the mechanisms that contribute to the high degree of invasiveness of breast cancer as it advances. According to Modi et al.[25], there is an important connection between inflammatory breast cancer and the dermal vasculature. They also proposed that the extent of dermal vascular involvement be clarified. Lin et al[26] concluded that BVI is an independent predictor of poor prognosis in operable breast cancer and is associated with aggressive clinicopathological features. CD34 is a currently recognized sensitive marker of tumor neovascular endothelium, which is present in the endothelial cells of microvessels[27]. In this study, we attempted to utilize CD34 IHC staining to identify LVI in breast cancer. The results of this research, however, did not support the hypothesis that the presence of tumor cells in the bloodstream causes organ metastases in breast cancer. The low sample size of the research and the restriction on the BVI detection rate by CD34 are potential causes of this. Consequently, more research is still required to confirm the correlation between vascular invasion and breast cancer.
Although our study provides novel insights into the predictive significance of LVI in breast cancer, there are limitations that must be taken into account. First off, selection bias could have occurred because all of the cases in this study originated from only one therapy center. Second, even though all study participants received the recommended course of treatments under the guidance and supervision of medical professionals and in accordance with breast cancer management guidelines, we cannot completely rule out the possibility that some patients' failure to comply with the recommended course of treatment due to the side effects of adjuvant therapy may have influenced the study's findings. Finally, the irregular structure of LVI led to a false-negative rate when we used D2-40 and CD34 for specific labeling of LVI in breast cancer. This was because it was impossible to ensure complete labeling of each LVI category during the sampling and staining process. Therefore, deeper investigations may be required to demonstrate the effect of LVI on the prognosis of breast cancer and the significance of specific vascular endothelial markers in research.