Various miRNAs play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared with normal breast tissues, and its expression levels were associated with increased survival outcome in patients with breast cancer. Overexpression of miR-204-5p inhibited viability, proliferation, and migration capacity in human and murine breast cancer cells. In addition, miR-204-5p overexpression resulted in a significant alteration in metabolic properties of cancer cells and suppression of tumor growth and metastasis in mouse breast cancer models. The association between miR-204-5p expression and clinical outcomes of patients with breast cancer showed a nonlinear pattern that was reproduced in experimental assays of cancer cell behavior and metastatic capacities. Transcriptome and proteomic analysis revealed that various cancer-related pathways including PI3K/Akt and tumor–immune interactions were significantly associated with miR-204-5p expression. PIK3CB, a major regulator of PI3K/Akt pathway, was a direct target for miR-204-5p, and the association between PIK3CB-related PI3K/Akt signaling and miR-204-5p was most evident in the basal subtype. The sensitivity of breast cancer cells to various anticancer drugs including PIK3CB inhibitors was significantly affected by miR-204-5p expression. In addition, miR-204-5p regulated expression of key cytokines in tumor cells and reprogrammed the immune microenvironment by shifting myeloid and lymphocyte populations. These data demonstrate both cell-autonomous and non-cell–autonomous impacts of tumor suppressor miR-204-5p in breast cancer progression and metastasis. Significance: This study demonstrates that regulation of PI3K/Akt signaling by miR-204-5p suppresses tumor metastasis and immune cell reprogramming in breast cancer.

Understanding the molecular background of breast cancer biology is critical in developing new biomarkers for earlier diagnosis and more optimized treatment. We performed a proteomic analysis of human breast carcinoma tissues to investigate the tumor‐specific protein expression in breast carcinoma. Using 2‐dimensional electorphoresis (2‐DE) and matrix‐assisted laser desorption/ionization‐time of flight‐mass spectrometry (MALDI‐TOF‐MS), we were able to identify a list of proteins which are upregulated in cancerous tissue. There was significant increase of galectin‐1 expression in all cancerous tissues compared to noncancerous tissues, and its increased expression was further confirmed by western blot immunostaining. Subsequent immunohistochemical staining against galectin‐1 in 105 breast cancer specimens showed significant correlation between galectin‐1 expression in cancer‐associated stromal cells and tumor invasiveness, T stage, TNM stage, and axillary lymph node metastasis. Galectin‐1 expressionin cancer cells showed no correlation to above‐mentioned pathologic variables. Hormonal receptor status and galectin‐1 expression showed no correlation. This study demonstrates the upregulation of galectin‐1 in breast carcinoma tissues and the clinical significance of galectin‐1 in breast cancer patients. Our data supports the recently highlighted roles of galectin‐1 in cancer‐associated stroma and in tumor immune privilege.

Purpose: The association between body mass index and breast cancer outcome is controversial. Furthermore, the impact of underweight on breast cancer recurrence and death has not been adequately addressed. Patients and Methods: We investigated this issue using a large nationwide database of 24,698 Korean breast cancer patients. The association between body weight status and breast cancer recurrence was further explored using a single-institution database containing information on 4,345 patients. Results: The results from the nationwide database showed significantly lower overall survival (OS) and breast cancer-specific survival (BCSS) in underweight patients compared with survival in patients of normal weight after adjusting for known prognostic factors such as age, tumor size, lymph node metastasis, hormone receptor status, histologic grade, and lymphovascular invasion (hazard ratio [HR], 1.48; 95% CI, 1.15 to 1.90 for OS; HR, 1.49; 95% CI, 1.15 to 1.93 for BCSS), which were not observed in obese patients. In an analysis of recurrence data from the single institution, underweight women had a significantly higher risk of both distant metastasis and local recurrence of breast cancer (HR, 1.93; 95% CI, 1.04 to 3.58 and HR, 5.13; 95% CI, 2.66 to 9.90, respectively). Conclusion: Our study suggests that underweight should be considered to be a high risk factor for death and recurrence after breast cancer surgery, especially in Asian breast cancer patients.