• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3911-3916
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• 2016

Background: Triple negative (TN) and triple positive (TP) breast cancers both are aggressive types but TN generally has a shorter survival. Objectives: To compare the clinical characteristics and treatment outcomes for patients with TN versus TP breast cancer and to assess various prognostic factors affecting overall survival. Materials and Methods: A retrospective audit of 85 breast cancer patients was conducted in the Department of Radiation Oncology and Medical Oncology on patients from 2006 to 2013 for whom IHC for ER, PgR and Her-2 neu were available. The patients were stratified into: ER-, PR- and Her-2 neu- (Arm A, n=47) and ER+, PgR+ and Her-2 neu+ (Arm B, n=38). Results: TN subtype had higher numbers of premenopausal and advanced stage patients as compared to TP subtype. The locoregional recurrence (LRR) and distant metastatic rate was also higher in TN subtype but there was no definite pattern in both the arms. Among the prognostic factors, patients with premenopausal status and advanced stage in TN breast cancer had inferior survival (P=0.07) whereas for those with postmenopausal status and early stage there was no survival difference between the two arms. Conclusions: TN subtype tends to be more aggressive in terms of younger age and advanced stage at presentation, higher tumour grade, LRR and metastasis, suggesting need for future research efforts on providing aggressive treatment to these patients. We could attribute better outcome for TP subtype to receptor positivity enabling role of hormonal treatment and targeted therapy, although less number of patients received targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5939-5944
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• 2015

Background: There is still a great deal of controversy with regard to the prognostic role of chemotherapy-induced amenorrhea (CIA) in breast cancer patients. To confirm whether CIA can serve as a useful factor in predicting clinical effects of systemic adjuvant chemotherapy, we performed this meta-analysis. Materials and Methods: Relevant studies were identified using PubMed, and Embase databases. Eligible study results were pooled and summary hazard ratios (HRs) with corresponding confidence intervals (CIs) were calculated. Subgroup analyses and an assessment of publication bias were also conducted. Results: A total of 8,333 patients from 11 published studies were identified through searching the databases. The pooled HRs for disease-free survival (DFS) suggested that CIA was associated with a significant reduction in the risk of recurrence, especially in patients with hormone receptor-positive lesions (overall HR=0.65, 95%CI 0.53-0.80, $I^2=41.3%$). When the five studies reporting the HR for overall survival (OS) were pooled (n=4193), a favorable trend was found (HR=0.69, 95%CI 0.52-0.91, $I^2=51.6%$). No publication bias was observed in this study. Conclusions: This meta-analysis suggests that CIA predicts a better outcome in premenopausal hormone receptor-positive breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8861-8869
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• 2014

Background: The prognostic value of Bcl-2 protein expression in non-small cell lung cancer (NSCLC) is under debate. We therefore systematically reviewed the evidence for Bcl-2 protein effects on NSCLC survival to elucidate this issue. Materials and Methods: An electronic search in Pubmed and Embase complemented by manual searches in article references were conducted to identify eligible studies to evaluate the association between Bcl-2 protein expression and overall survival (OS) as well as disease free survival (DFS) of NSCLC patients. Combined hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were pooled using the random-effects model. Results: A total of 50 trials (including 52 cohorts) encompassing 7,765 patients were pooled in the meta-analysis regarding Bcl-2 expression and OS of NSCLC patients. High expression of Bcl-2 protein had a favorable impact (HR=0.76, 95%CI=0.67-0.86). In the group of Bcl-2 expression and DFS, 11 studies including 2,634 patients were included. The synthesized result indicated high expression of Bcl-2 protein might predict good DFS (HR=0.85, 95%CI=0.75-0.95). Conclusions: Our present meta-analysis demonstrated favorable prognostic values of Bcl-2 expression in patients with NSCLC. Further prospective trails are welcomed to validate the utility of assessing Bcl-2 in NSCLC patient management.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8923-8929
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• 2014

Background: Increasing evidence suggests that stromal monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX) may play key roles in tumor development. However, their clinical value remains largely unexplored in gastric cancer (GC). The present study aimed to determine clinicopathological significance and prognostic values of stromal MCT4 and CA IX in GC. Materials and Methods: Specimens from 143 GC patients were immunohistochemically stained using polyclonal anti-MCT4 and anti-CA IX antibodies. Expression was correlated with patient clinicopathologic characteristics and survival data. Results: High stromal MCT4 expression was detected in 72 of 143 (50.3%) GCs and high CA IX in 74 (51.7%). Both high stromal MCT4 and CA IX were correlated with advanced TNM stage (p=0.000; p=0.000). High CA IX expression was positively related to depth of invasion (p=0.022) and positive lymph nodes (p=0.002) as well. Survival analysis indicated high expression of stromal MCT4 to be an independent factor in predicting poor overall survival (OS) (HR and 95%CI=1.962, 1.032-3.729, p=0.040) and disease free survival (DFS) (HR and 95%CI=2.081, 1.158-3.741, p=0.014) of GC patients. However, high CA IX expression exhibited no significant predictive value. Conclusions: These findings suggest that high expression of stromal MCT4 and CA IX proteins is significantly correlated with GC progression. High stromal MCT4 heralds worse outcome of GC patient, suggesting a novel candidate prognostic marker and therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4711-4715
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• 2013

Aim: The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensitymodulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer. Methods: Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed. Results: After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ${\geq}$ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival ($X^2$ = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05). Conclusions: IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1553-1558
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• 2015

Background: COX-2 has been shown to play an important role in the development of breast cancer and increased expression has been mooted as a poor prognostic factor. The purpose of this study was to investigate the relationship between COX-2 immunohistochemical expression and known predictive and prognostic factors in breast cancer in a routine diagnostic histopathology setting. Materials and Methods: Formalin-fixed paraffin-embedded tumour tissue of 144 no special type (NST) invasive breast carcinomas histologically diagnosed between January 2009 and December 2012 in Hospital Sultanah Bahiyah, Alor Setar, Kedah were immunostained with COX-2 antibody. COX-2 overexpression was analysed against demographic data, hormone receptor status, HER2-neu overexpression, histological grade, tumour size and lymph node status. Results: COX-2 was overexpressed in 108/144 (75%) tumours and was significantly more prevalent (87%) in hormone receptor-positive tumours. There was no correlation between COX-2 overexpression and HER2/neu status. Triple negative cancers had the lowest prevalence (46%) (p<0.05). A rising trend of COX-2 overexpression with increasing age was observed. There was a significant inverse relationship with tumour grade (p<0.05), prevalences being 94%, 83% and 66% in grades 1, 2 and 3 tumours, respectively. A higher prevalence of COX-2 overexpression in smaller size tumours was observed but this did not reach statistical significance. There was no relationship between COX-2 expression and lymph node status. Conclusions: This study did not support the generally held notion that COX-2 overexpression is linked to poor prognosis, rather supporting a role in tumorigenesis. Larger scale studies with outcome data and basic studies on cancer pathogenetic pathways will be required to cast further light on whether COX-2 inhibitors would have clinical utility in cancer prevention or blockage of cancer progression. In either setting, the pathological assessment for COX-2 overexpression in breast cancers would have an important role in the selection of cancer patients for personalized therapy with COX-2 inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1435-1442
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• 2015

Purpose: To study the patient load, treatment pattern, survival outcome and its predictors in patients with brain metastases treated by radiotherapy. Materials and Methods: Data for patients with brain metastases treated by radiotherapy between 2003 and 2007 were collected from medical records, the hospital information system database, and a population-based tumor registry database until death or at least 5 years after treatment and retrospectively reviewed. Results: The number of treatments for brain metastases gradually increased from 48 in 2003 to 107 in 2007, with more than 70% from lung and breast cancers. The majority were treated with whole brain radiation of 30 Gy (3 Gy X 10 fractions) by cobalt-60 machine, using radiation alone. The overall median survival of the 418 patients was 3.9 months. Cohort analysis of relative survival after radiotherapy was as follows: 52% at 3 months, 18% at 1 year and 3% at 5 years in males; and 66% at 3 months, 26% at 1 year and 7% at 5 years in females. Multivariate analysis demonstrated that the patients treated with combined modalities had a better prognosis. Poor prognostic factors included primary cancer from the lung or gastrointestinal tract, emergency or urgent consultation, poor performance status (ECOG 3-4), and a hemoglobin level before treatment of less than 10 g/dl. Conclusions: This study identified an increasing trend of patient load with brain metastases. Possible over-treatment and under-treatment were demonstrated with a wide range of survival results. Practical prognostic scoring systems to assist in decision-making for optimal treatment of different patient groups is absolutely necessary; it is a key strategy for balancing good quality of care and patient load.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2355-2362
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• 2012

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2967-2971
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• 2013

Background: Extraskeletal Ewing sarcoma (EES)/primitive neuroectodermal tumours (PNET) are rare soft tissue sarcomas. Prognostic factors and optimal therapy are still unconfirmed. Materials and Methods: We performed a retrospective analysis on patients to explore the clinic characteristics and prognostic factors of this rare disease. A total of 37 patients older than 15 years referred to our institute from Jan., 2002 to Jan., 2012 were reviewed. The characteristics, treatment and outcome were collected and analyzed. Results: The median age was 28 years (range 15-65); the median size of primary tumours was 8.2 cm (range 2-19). Sixteen patients (43%) had metastatic disease at the initial presentation. Wide surgical margins were achieved in 14 cases (38%). Anthracycline or platinum-based chemotherapy was performed on 29 patients (74%). Radiotherapy was delivered in 13 (35%). At a median follow-up visit of 24 months (range 2-81), the media event-free survival (EFS) and overall survival (OS) were 15.8 and 30.2 months, respectively. The 3-year EFS and OS rates were 24% and 43%, respectively. Metastases at presentation and wide surgical margins were significantly associated with OS and EFS. Tumour size was significantly associated with OS but not EFS. There were no significant differences between anthracycline and platinum based chemotherapy regarding EFS and OS. Conclusions: EES/PNET is a malignant tumour with high recurrence and frequent distant metastasis. Multimodality therapy featuring wide surgical margins, aggressive chemotherapy and adjuvant local radiotherapy is necessary for this rare disease. Platinum-based chemotherapy can be used as an adjuvant therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2851-2857
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• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.