PurposeT-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role.MethodsImmunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed.ResultsTIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%–25%), 48 cases (26%–50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296–0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314–0.3912; p=0.0006).ConclusionIn this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.
Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.
Background: The principal objective of this study was to assess clinical outcomes by breast cancer subtype in patients with brain metastases. Methods: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status was evaluated via immunohistochemical staining. Four survival time intervals were compared according to the subtype (ER+/HER2–, HER2+, triple negative (TN)). Results: 20 (30.3%) of the 66 patients in this study were ER+/HER2–, 20 (30.3%) were HER2+, and 26 (39.4%) were TN. The disease-free survival rates of ER+/HER2–, HER2+, and TN patients were 30.0, 17.0, and 17.9 months, respectively (p = 0.040). The median time intervals from distant metastasis to brain metastasis were 20.6, 19.5, and 9.0 months, respectively (p = 0.012). The times from initial diagnosis to brain metastasis were 52.9, 33.6, and 25.5 months, respectively (p = 0.026). However, the overall survival rates did not differ significantly (p = 0.276). Conclusions: Patients with TN breast cancer were more likely to develop distant metastasis earlier, and also evidenced poor overall survival. Triple receptor status may be employed as a prognostic marker for breast cancer patients with brain metastases.
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