Androgen receptor/let-7a signaling regulates breast tumor-initiating cells.

Androgen receptor (AR) is an important transcriptional factor, which is frequently expressed in invasive breast cancer and correlates patients' prognosis. Our previous results indicate AR activation may increase let-7a expression in breast cancer cells, while let-7, a tumor suppressor, is reported to inhibit breast tumor-initiating cells (T-IC). The study aims to explore the effects of AR/let-7a signaling on breast T-IC and its regulatory mechanism. The results revealed that the expression of AR was significantly associated with let-7a and CD44+/24-/low especially in estrogen receptor positive (ER+) breast cancer tissues. The expression of AR and let-7a indicated better outcome, while patients with CD44+/24-/low phenotype had worse prognosis. AR activation induced by dihydrotestosterone (DHT) prevented cells proliferation, migration, invasion and self-renewal capacities in ER+ breast cancer cells, via transcriptional up-regulation of let-7a. In addition, AR could inhibit tumorigenesis and metastasis of ER+ breast cancer cells in the serial xenotranplanted animal models. Our data suggested that AR/let-7a signaling could inhibit the biological behavior of tumor-initiating cells (T-IC) in ER+AR+ breast cancers, which might become a new therapeutic target.

Androgen receptor and metastasis-associated protein-1 are frequently expressed in estrogen receptor negative/HER2 positive breast cancer.

The prognostic value of androgen receptor (AR) and its related molecules in breast cancer is not well characterized. We retrospectively investigated 120 ER(+) and 120 ER(-) invasive breast cancers of 240 women, who were treated at our institution between January 2008 and December 2009. We excluded in situ, recurrent, metastatic, and bilateral carcinomas as well as non-epithelial lesions. Median follow-up was 74 months. Immunohistochemical assessment of expression of AR and metastasis-associated protein-1 (MTA1) resulted in 59.2 % (n = 142) AR(+) and 36.7 % (n = 88) high MTA1 expressing (MTA1(High)) carcinomas. MTA1(High) tumors were significantly more often ER(-), while AR(+) tumors were significantly more often HER2(+) (p < 0.01). MTA1(High)/ER(-) tumors were more often AR(-)/HER2(-) (p < 0.01). Patients with an AR(+)/ER(+) tumor had better disease-free survival (DFS; p = 0.011). Patients with an ER(-)/MTA1(High) tumor had significantly shorter DFS (p = 0.006) as well as patients with an AR(+)/HER2(+) tumor (p < 0.01). In Cox models, AR expression (HR, 0.248; 95 % CI, 0.086-0.716) and lymph node status (HR, 6.401; 95 % CI, 1.428-28.686) were independent predictors for DFS in ER(+) cancers, whereas AR(+)/HER2(+) expression status (HR, 2.927; 95 % CI, 1.256-6.821) and lymph node status (HR, 2.690; 95 % CI, 1.041-7.840) were independent predictors for DFS in ER(-) cancers. We show that AR might be an additional marker for endocrine responsiveness in ER(+) cancers and suggests that blocking MTA1 might be an effective way to inhibit AR/HER2 signaling in ER(-) breast cancer.

Loss of FAT1 during the progression from DCIS to IDC and predict poor clinical outcome in breast cancer.

FAT1 and ß-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 ß-catenin in breast cancer tissues from 113 cases of DCIS and 149 cases of IDC. As compared with DCIS, expression of FAT1 and ß-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 ß-catenin subgroup. Furthermore, expressions of FAT1 and ß-catenin were correlated with each other in DCIS and IDC (P<0.05). FAT1(-), ß-catenin(-), or FAT1(-)/ß-catenin(-) may indicate worse DFS and OS in breast cancer (P<0.05). This study suggests that loss of FAT1 and ß-catenin are associated with breast cancer progression, aggressive behavior, and poor prognosis. FAT1 alone or together with ß-catenin might be a valuable biomarker in predicting the prognosis of patients with breast cancer.

Postmastectomy radiotherapy benefit in Chinese breast cancer patients with T1-T2 tumor and 1-3 positive axillary lymph nodes by molecular subtypes: an analysis of 1369 cases.

The aim of this study was to examine the association between molecular subtype (MST) and prognosis and research the postmastectomy radiotherapy (PMRT) effect in T1-T2 tumors with 1-3 positive axillary lymph nodes (ALNs). This retrospective study studied breast cancer patients with T1-T2 tumors and 1-3 positive ALNs according to MST: Luminal A, Luminal B, human epidermal growth factor receptor-2 (Her-2) positive, and Triple negative. The impact of adjuvant PMRT in T1-T2 tumors with 1-3 positive ALNs was also assessed. This study included 1369 patients: 33.0 % Luminal A, 42.9 % Luminal B, 11.9 % Her-2 positive, and 12.2 % Triple negative. On univariate and multivariate analyses, MST was associated with locoregional relapse (LRR). Kaplan-Meier analysis showed that PMRT significantly decreased LRR risk (p = 0.017) and distant metastasis (DM) risk (p < 0.0001). In subgroup analysis, PMRT showed significant benefits of improvement in LRR in patients with younger age, positive lymphovascular invasion (LVI), and ratio of positive lymph nodes (LNs) >25 %. Moreover, the nomogram could more accurately predict LRR (c-index 0.75) in T1-2N1 breast cancer patients. MST associated with patient outcomes in breast cancer patients with T1-T2 tumors and 1-3 positive ALN. It makes sense to offer PMRT for patients aged<40 years old, LVI, 2 and 3 positive lymph nodes, and ratio of positive LNs >25 %.

[Value of CK5/6, CK14, ER and PR detection in differential diagnosis of intraductal proliferative lesions of the breast].

OBJECTIVE: To investigate the expression of high-molecular-weight keratins CK5/6, CK14, estrogen receptor (ER) and progesterone receptor (PR) in differential diagnosis of simple ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (low-grade DCIS) . METHODS: The clinicopathological data of twenty cases of atypical ductal epithelial hyperplasia (ADH) with focal cancerization changed into low-grade DCIS diagnosed at Tianjin Medical University Cancer Institute and Hospital between January 2013 and February 2014 were reviewed and analyzed. The expressions of CK5/6, CK14, ER and PR were detected by immunohistochemistry. RESULTS: Positive expressions of CK5/6 and CK14 were seen in UDH showing a mosaic pattern, while negative expression in ADH and low-grade DCIS. In addition, CK5/6 and CK14 were positively expressed in the myoepithelial cells of UDH, ADH and low-grade DCIS. Positive expressions of ER and PR were observed in UDH, ADH and low-grade DCIS. But they presented diffuse and homogeneous strong positive expression in ADH and variable positive expression in UDH. CONCLUSION: In the intraductal proliferative lesions of the breast, the use of combined detection of the expression of CK5/6, CK14, ER and PR is of practical significance in the differential diagnosis of UDH, ADH and low-grade DCIS.

Breast metastasis from lung cancer: a report of two cases and literature review.

Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4% to 1.3% has been reported in literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. In this report, two cases of pulmonary metastasis to the breast were presented. A 40-year-old female manifested a right breast mass of 2-month duration. After physical examination was performed, a poorly defined mass was noted in the upper outer quadrant of the right breast. Another 49-year-old female manifested right breast mass of 5-day duration. A poorly defined mass was noted in the lower inner quadrant of the right breast. Mammography results also revealed breast cancer. The patients underwent local excision. After histological and immunohistochemical analyses were conducted, a primary lung carcinoma that metastasized to the breast was diagnosed. An accurate differentiation of metastasis to the breast from primary breast cancer is very important because the treatment and prognosis of the two differ significantly.