Primary apocrine sweat gland carcinoma (PASGC) is an extremely rare malignancy with a relatively favorable prognosis. PASGC is often suspected to be a benign disease during an initial clinical examination, which leads to inadequate initial treatment and extensive metastasis. Owing to the limited number of reports on PASGC, its diagnostic criteria and treatment guidelines have not yet been established. The only known curative therapy for localized PASGC is wide local excision. In the present report, we describe two cases of PASGC with locally aggressive disease that arose in the axilla and review the literature about its clinicopathological features, diagnosis, and treatment. Based on the findings of the current report, we suggest that a sentinel lymph node biopsy and adjuvant anti-estrogen therapy should be included in the management of PASGC.

Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells.

B-cell lymphoma-2 (Bcl-2) is one of the most important anti-apoptotic genes. Although Bcl-2 promotes tumor cell survival in vitro, previous studies have shown conflicting results regarding the association between Bcl-2 and breast cancer survival. The aim of this study was to assess the prognostic significance of Bcl-2 according to the molecular tumor subtype in primary invasive breast cancer patients. The relationship between immunohistochemical Bcl-2 expression and overall survival was analyzed in 2399 primary invasive breast cancer patients treated by curative surgery. Patients were classified into four subtypes based on hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) status: HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. A total of 1304 patients (54.4 %) had Bcl-2 positive (+) tumors by immunohistochemistry. Bcl-2 (+) tumors were significantly associated with a younger age (<50 years), early stage, lower grade, positive expression of HR, and negative expression of HER2. In the HR+/HER2- group, patients with Bcl-2 (+) tumors showed a significantly better prognosis (p < 0.001). In contrast, there was no significant prognostic effect of Bcl-2 expression in other subtypes. In multivariate analysis, Bcl-2 positivity remained an independent, favorable prognostic factor in the HR+/HER2- subtype (hazard ratio, 0.609; 95 % confidence interval, 0.424-0.874; p < 0.007). The prognostic significance of Bcl-2 expression differed according to the molecular subtype of breast cancer. The expression of Bcl-2 was an independent, favorable prognostic factor in breast cancer patients with the HR+/HER2- subtype.

Metabolic reprogramming in cancer cells has recently been recognized as an essential hallmark of neoplasia. In this context, metabolic alterations represent an attractive therapeutic target, and encouraging results with drugs targeting various metabolic processes have been obtained in preclinical studies. Recently, several studies have suggested that dichloroacetate (DCA), a specific pyruvate dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large number of diverse tumors. However, the precise mechanism is not fully understood, which is important for the use of DCA in cancer treatment. In the present study, we found that DCA sensitized MCF7 breast cancer cells to tamoxifen-induced cell death by decreasing epidermal growth factor receptor (EGFR) expression. The downregulation of EGFR was caused by degradation of the protein. Furthermore, p38 mitogen-activated protein kinase played an important role in DCA/tamoxifen-induced EGFR degradation. Finally, DCA also promoted comparable tamoxifen-induced cell death in tamoxifen-resistant MCF7 cells, which were established by long-term treatment with tamoxifen. In summary, our results suggest that DCA is an attractive potential drug that sensitizes cells to tamoxifen-induced cell death and overcome tamoxifen resistance via downregulation of EGFR expression in breast cancer cells.

PurposeThis study aimed to evaluate the survival benefit of different adjuvant chemotherapy regimens in patients with T1-2N0 triple-negative breast cancer.MethodsOf 67,321 patients who were registered in the Korean Breast Cancer Society nationwide database between January 1999 and December 2008, 4,033 patients with T1-2N0 triple-negative breast cancer were included. The overall survival of patients who did not receive adjuvant chemotherapy was compared with those treated with adjuvant anthracycline and cyclophosphamide (AC), 5-fluorouracil, anthracycline, and cyclophosphamide (FAC), or cyclophosphamide, methotrexate, and 5-fluorouracil (CMF).ResultsThe median follow-up was 52.5 months. Chemotherapy was used in 87.4% of patients; it was used more commonly in patients with T2 tumors, those who were younger, had a higher histologic grade, and who showed lymphovascular invasion. The 5-year cumulative overall survival rate was 95.4%. Younger age, breast-conserving surgery, and adjuvant chemotherapy were significantly associated with improved overall survival. The 5-year cumulative overall survival rate of patients who did not receive adjuvant chemotherapy and those treated with AC, FAC, and CMF were 92.5%, 95.9%, 95.3%, and 95.9%, respectively. On multivariate analysis, the administration of any adjuvant chemotherapy regimen was significantly associated with improved overall survival (p=0.038). No significant difference in survival benefit was observed among the three different treatment groups.ConclusionA standard adjuvant chemotherapy regimen with the least drug-related toxicity might be a reasonable treatment for patients with T1-2N0 triple-negative breast cancer.