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AR-expressing TNBCs represent a distinct breast cancer subgroup with adverse clinical outcome and AR blockade could be a potential endocrine therapy for these TNBC patients. Evaluation of AR status may provide additional information on prognosis and treatment in patients with TNBC.

BackgroundThe association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined.MethodsWe analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox’s proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories.ResultsA U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals.ConclusionsWe observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules.

IBC with NE differentiation is a distinct subtype of mammary carcinoma with an aggressive clinical outcome.

Purpose The axillary reverse mapping (ARM) technique to identify and preserve arm nodes during sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) was developed to prevent lymphedema. The purpose of this study was to investigate the location and metastatic rate of the arm node, and to evaluate the short term incidence of lymphedema after arm node preserving surgery. Methods From January 2009 to October 2010, 97 breast cancer patients who underwent ARM were included. Blue-dye (2.5 mL) was injected into the ipsilateral upper-inner arm. At least 20 minutes after injection, SLNB or ALND was performed and blue-stained arm nodes and/or lymphatics were identified. Patients were divided into two groups, an arm node preserved group (70 patients had ALND, 10 patients had SLNB) and an unpreserved group (13 patients had ALND, 4 patients had SLNB). The difference in arm circumference between preoperative and postoperative time points was checked in both groups. Results The mean number of identified blue stained arm nodes was 1.4±0.6. In the majority of patients (92%), arm nodes were located between the lower level of the axillary vein and just below the second intercostobrachial nerve. In the arm node unpreserved group, 2 patients had metastasis in their arm node. Among ALND patients, in the arm node preserved group, the difference in arm circumference between preoperative and postoperative time points in ipsilateral and contralateral arms was 0.27 cm and 0.07 cm, respectively, whereas it was 0.47 cm and -0.03 cm in the unpreserved group; one case of lymphedema was found after 6 months. No difference was found between arm node preserved and unpreserved group among SLNB patients. Conclusion Arm node preserving was possible in all breast cancer patients with identifiable arm nodes, during ALND or SLNB, except for those with high surgical N stage, and lymphedema did not develop in patients with arm node preserving surgery.

Regulator of G protein signaling 2 (RGS2) is a member of a family of proteins that functions as a GTPase-activating protein (GAP) for Gα subunits. RGS2 mRNA expression is lower in breast cancerous tissues than in normal tissues. In addition, expression of RGS2 is also lower in MCF7 (cancerous breast cells) than in MCF10A (normal breast cells). Here we investigated whether RGS2 inhibits growth of breast cancer cells. RGS2 overexpression in MCF7 cells inhibited epidermal growth factor- or serum-induced proliferation. In HEK293T cells expressing RGS2, cell growth was also significantly suppressed (In addition, exogenous expression of RGS2 in HEK293T cells resulted in the significant suppression of cell growth). These results suggest that RGS2 may have a tumor suppressor function. MG-132 treatment of MCF7 cells increased endogenous or exogenous RGS2 levels, suggesting a post-transcriptional regulatory mechanism that controls RGS2 protein levels. RGS2 protein was degraded polyubiquitinated the K71 residue, but stabilized by deubiquitinase monocyte chemotactic protein-induced protein 1 (MCPIP1), and not affected by dominant negative mutant (C157A) of MCPIP1. Gene expression profiling study showed that overexpression of RGS2 decreased levels of testis specific Y encoded like protein 5 (TSPYL5), which plays a causal role in breast oncogenesis. TSPYL5 protein expression was low in MCF10A and high in MCF7 cells, showing the opposite aspect to RGS2 expression. Additionally, RGS2 or MCPIP1 overexpression in MCF7 cells decreased TSPYL5 protein level, indicating that RGS2 stabilized by MCPIP1 have diminished TSPYL5 protein levels, thereby exerting an inhibitory effect of breast cancer cell growth.

PurposeCancer tissue may display a wide spectrum of expression phenotypes of epithelial-mesenchymal transition (EMT)-related proteins. The purpose of this study was to investigate the clinical significance of EMT phenotypes in breast cancer.MethodsWe evaluated the expression pattern of the EMT-related proteins E-cadherin and fibronectin in samples from 1,495 patients with invasive breast carcinoma (IBC) on tissue microarrays using immunohistochemistry to investigate the clinical significance of EMT phenotypes in IBC. EMT phenotypes were divided into complete type (E-cadherin-negative/fibronectin-positive), incomplete type (hybrid type, E-cadherinpositive/fibronectin-positive; null type, E-cadherin-negative/fibronectin-negative), and wild-type (E-cadherin-positive/fibronectin-negative). We analyzed the correlation of EMT phenotype with clinicopathological factors and patient survival.ResultsLoss of E-cadherin was observed in 302 patients (20.2%), and fibronectin was expressed in the cancer cells of 354 patients (23.7%). In total, 64 (4.3%), 290 (19.4%), 238 (15.9%), and 903 (60.4%) samples were categorized as complete, hybrid, null, and wild-type, respectively. The complete EMT phenotype exhibited significant associations with young age (p=0.017), advanced pT (p<0.001) and pN (p<0.001) stages, higher histological grade (p<0.001), lymphovascular invasion (p<0.001), and triple negativity (p<0.001). Patients with complete and hybrid EMT phenotypes had poorer overall survival (OS) and disease-free survival (DFS) than those with the wild-type phenotype (OS, p=0.001; DFS, p<0.001). In multivariate analysis, the hybrid EMT phenotype was an independent prognostic factor for DFS in patients with IBC (p=0.032).ConclusionEMT phenotypes exhibited significant associations with clinicopathological factors indicating aggressive biologic behavior and poor outcome in patients with IBC.

Measurements of TIL density in routine clinical practice could give useful prognostic information for the triple-negative, HER2-positive, and luminal B (HER2-negative) IBC subtypes, especially for patients administered adjuvant anthracycline.