It is generally known that the decision to use anti-estrogen therapy is based on the expression of estrogen and progesterone receptors in breast cancers. Recent studies have shown that androgen receptor (AR) is frequently expressed in ER-, PR- breast cancer and plays an important role in the prognosis of breast cancer patients. Furthermore, AR can increase the global expression of microRNAs, post-transcriptional gene regulators that play a crucial role in the initiation and progression of breast cancer. In this study, we investigated the functions and relations of AR, related miRNAs and target proteins in ER-, PR-, AR+ breast cancer. The results showed that androgen-induced AR activating signal directly upregulates let-7a expression, downregulates CMYC and KRAS protein expression, and inhibits cell proliferation in ER-, PR-, AR+ breast cancer cells. Overexpression of let-7a inhibits cell proliferation and downregulates CMYC and KRAS protein expression, whereas inhibition of let-7a expression by specific antisense oligonucleo-tides increases cell growth and upregulates CMYC and KRAS protein expression. We performed in situ hybridization for let-7a and immunohistochemical staining for CMYC and KRAS using sequential sections obtained from surgically-resected breast cancer tissues and observed an inverse correlation between the staining pattern of let-7a and its target proteins. Androgen-induced AR activating signal upregulates let-7a that targets CMYC and KRAS and contributes to ER-, PR-, AR+ breast cancer pathogenesis. Elucidation of this pathway will help develop new therapies.

Patients with microinvasive carcinoma often have favorable prognosis, but it remains unclear whether this special type of breast cancer represents a distinct morphological entity with its own biological features and clinical behavior distinct from those of ductal carcinoma in situ (DCIS). The study is a retrospective analysis of a large patient cohort from a single institution. One hundred and thirty one microinvasive carcinoma and 451 DCIS cases were collected. ER, PR, HER2, and Ki67 were examined by immunohistochemistry in pathological sections. We assessed the clinicopathologic characteristics, molecular features, and survival status of microinvasive carcinoma and compared to those of DCIS. Microinvasive carcinoma differed from DCIS with respect to tumor size, lymph node status, and initial presentation (P < 0.05). There was a significant difference in nuclear grade among microinvasive carcinoma of different molecular subtype (P < 0.05). The clinicalpathologic features and outcomes of patients with microinvasive carcinoma were similar to those with DCIS. The 5-year OS rate for microinvasive carcinoma and DCIS patients was 99.0 and 99.2%, respectively. A combination of pathologic, clinical, and molecular factors may ultimately reveal more powerful and robust measures for disease classification than any one modality alone. Microinvasive carcinoma does not significantly predict for worse DFS or OS in comparison with patients with DCIS.

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FAT1 and β-catenin are important tumor regulatory factors. The aim of this study was to detect the possible disparity in their expression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) and to explore its correlation with clinicopathological factors. We used immunohistochemistry to detect protein expression of FAT1 and β-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and β-catenin were significantly decreased in IDC (P<0.05). In addition, our study also revealed a correlation between their expression and some clinicopathological factors. We found that FAT1 expression was associated with nuclear grade and comedonecrosis (P<0.05) in DCIS, whereas FAT1 expression showed significant variation with histological grade and LN status (P<0.05) in IDC. Similar associations were observed in the β-catenin subgroup. Furthermore, expressions of FAT1 and β-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), β-catenin(-), or FAT1(-)/β-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and β-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with β-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.