Bcl-2 is a highly significant prognostic marker of hormone-receptor-positive, human epidermal growth factor receptor-2-negative breast cancer.

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.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients.

PURPOSE: The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor. METHODS: Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay. RESULTS: Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%. CONCLUSION: Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.

Phosphorylated S6 kinase-1: a breast cancer marker predicting resistance to neoadjuvant chemotherapy.

BACKGROUND: Pre-clinical data support a link between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and chemoresponsiveness. We evaluated whether the expression of phosphorylated AKT (p-AKT) or phosphorylated S6 kinase-1 (p-S6K1), a key effector of the mTOR pathway, could be a predictive marker for chemoresponsiveness in breast cancer. PATIENTS AND METHODS: A total of 209 patients with locally advanced breast cancer who received neoadjuvant chemotherapy between April 2005 and July 2012 were analyzed. Patients without a minimum of 10% tumor reduction, after neoadjuvent chemotherapy, were classified as non-responders. RESULTS: Overall, 184 (88%) patients were classified as responders and 25 (12%) as non-responders. The positive expression rate for p-AKT and p-S6K1 was 31.6% and 45%, respectively. There was no difference in the pre-chemotherapy clinical stage according to p-S6K1 or p-AKT expression status. p-AKT expression was slightly higher in non-responders compared to responders (48% vs. 30.9%; p=0.088). However, p-S6K1 expression was significantly higher in non-responders than responders (68% vs. 41.8%; p=0014). Following multivariate analysis, p-S6K1 positivity remained an independent predictor of non-responder status (hazard ratio=3.81; 95% confidence interval=1.28-11.31; p=0.016). CONCLUSION: The expression of p-S6K1 may be a predictive marker of resistance to neoadjuvant chemotherapy in patients with breast cancer.

Incidence and risk factors of parastomal hernia.

PURPOSE: Among the various stoma complications, the parastomal hernia (PSH) is the most common. Prevention of PSH is very important to improve the quality of life and to prevent further serious complications. The aim of this study was to analyze the incidence and the risk factors of PSH. METHODS: From January 2002 and October 2008, we retrospectively reviewed 165 patients who underwent an end colostomy. As a routine oncologic follow-up, abdomino-pelvic computed tomography was used to examine the occurrence of the PSH. The associations of age, sex, body mass index (BMI), history of steroid use and comorbidities to the development of the PSH were analyzed. The median duration of the follow-up was 36 months (0 to 99 months). RESULTS: During follow-up, 50 patients developed a PSH and the 5-year cumulative incidence rate of a PSH, obtained by using the Kaplan-Meier method, was 37.8%. In the multivariate COX analysis, female gender (hazard ratio [HR], 3.29; 95% confidence interval [CI], 1.77 to 6.11; P < 0.0001), age over 60 years (HR, 2.37; 95% CI, 1.26 to 4.46; P = 0.01), BMI more than 25 kg/m(2) (HR, 1.8; 95% CI, 1.02 to 3.16; P = 0.04), and hypertension (HR, 2.08; 95% CI, 1.14 to 3.81; P = 0.02) were all independent risk factors for the development of a PSH. CONCLUSION: The 5-year incidence rate of a PSH was 37.8%. The significant risk factors of a PSH were as follows: female gender, age over 60 years, BMI more than 25 kg/m(2), and hypertension. Using a prophylactic mesh during colostomy formation might be advisable when the patients have these factors.