Lymphovascular invasion in colorectal cancers: can we predict it preoperatively?

PURPOSE: This study aimed to investigate preoperative predictors of lymphovascular invasion (LVI), which is a poor prognostic factor usually detected postoperatively in patients with colorectal cancer. METHODS: Results for all patients operated on for colorectal cancer between January 1, 2006, and December 31, 2021, were retrospectively analyzed. Potential preoperative factors and postoperative pathology results were recorded. The patients were categorized as those with LVI and those without LVI. Potential factors that may be associated with LVI were compared between the 2 groups. RESULTS: The study included 335 patients. The incidence of LVI was 3.11 times higher in patients with ascending colon tumors (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.34-7.23; P=0.008) and 4.28 times higher in those with metastatic tumors (OR, 4.28; 95% CI, 2.18-8.39; P<0.001). Diabetes mellitus was inversely related to LVI in colorectal cancer patients; specifically, LVI was 56% less common in colorectal cancer patients with diabetes mellitus, irrespective of its duration (OR, 0.44; 95% CI, 0.25-0.76; P<0.001). CONCOUSION: The presence of preoperative LVI in colorectal cancer patients is difficult to predict. In particular, the effect of the effect of factors such as chronic disease accompanied by microvascular pathologies on LVI is still unclear. Advances in the neoadjuvant treatment of colorectal cancer patients, who are becoming more widespread every day, will encourage the investigation of different methods of preoperatively predicting LVI as a poor prognostic factor in these patients.

Better Local Disease Control With Mastectomy in Metaplastic Breast Carcinoma: Findings of a Retrospective Cohort.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare type of breast carcinoma with clinicopathological differences. The prognosis and treatment strategies for MBC are usually conflicting. In this study, we aim to present the clinicopathologic features, treatment strategies, and prognosis of our MBC patients. MATERIAL AND METHODS: In our retrospective study, 18 metaplastic breast cancer patients treated in our institution between January 2005 and December 2022 were evaluated. Demographic and clinicopathological characteristics, surgical and systemic treatment options, locoregional recurrences, distant metastases, and overall survival (OS) of the MBC patients were retrieved from the patient files. RESULTS: All patients were female; the median age was 54.42 ± 12.37 years. Most of the patients (n = 15, 83.33%) presented with palpable masses. Tumors were mostly triple-negative, with a high grade and a high Ki­67 proliferation index. Spindle cell carcinoma and MBC with mesenchymal differentiation were the most common subtypes. Most of the patients underwent mastectomy (n = 11, 61.11%); breast-conserving surgery (BCS) was performed on seven (38,88%) patients. Lymph node positivity was detected in six of 18 patients (33.33%). Fewer patients (n = 4, 22.22%) received neoadjuvant chemotherapy. While local recurrence developed in two out of seven patients (28.57%) who underwent BCS, there was no local recurrence in patients who had mastectomy. The OS time varied according to tumor size and the presence of lymph node metastases (p <0.001; p = 0.005). CONCLUSION: Metaplastic breast cancer is genetically heterogeneous and resistant to conventional treatment strategies. Mastectomy is still the surgical treatment method that is performed more frequently and provides better local control for patients with metaplastic breast cancer.

Dual activity of Minnelide chemosensitize basal/triple negative breast cancer stem cells and reprograms immunosuppressive tumor microenvironment.

Triple negative breast cancer (TNBC) subtype is characterized with higher EMT/stemness properties and immune suppressive tumor microenvironment (TME). Women with advanced TNBC exhibit aggressive disease and have limited treatment options. Although immune suppressive TME is implicated in driving aggressive properties of basal/TNBC subtype and therapy resistance, effectively targeting it remains a challenge. Minnelide, a prodrug of triptolide currently being tested in clinical trials, has shown anti-tumorigenic activity in multiple malignancies via targeting super enhancers, Myc and anti-apoptotic pathways such as HSP70. Distinct super-enhancer landscape drives cancer stem cells (CSC) in TNBC subtype while inducing immune suppressive TME. We show that Minnelide selectively targets CSCs in human and murine TNBC cell lines compared to cell lines of luminal subtype by targeting Myc and HSP70. Minnelide in combination with cyclophosphamide significantly reduces the tumor growth and eliminates metastasis by reprogramming the tumor microenvironment and enhancing cytotoxic T cell infiltration in 4T1 tumor-bearing mice. Resection of residual tumors following the combination treatment leads to complete eradication of disseminated tumor cells as all mice are free of local and distant recurrences. All control mice showed recurrences within 3 weeks of post-resection while single Minnelide treatment delayed recurrence and one mouse was free of tumor. We provide evidence that Minnelide targets tumor intrinsic pathways and reprograms the immune suppressive microenvironment. Our studies also suggest that Minnelide in combination with cyclophosphamide may lead to durable responses in patients with basal/TNBC subtype warranting its clinical investigation.