Vascular endothelial growth factor ­634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.

Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ­2578C/A, ­1498C/T, ­1154G/A and ­634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi­quantitative RT­PCR. The genotypes, ­634G/C and ­634C/C, were associated with an increased risk for breast cancer when compared with the ­634G/G genotype. The VEGF ­634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II­IV. Individuals with ­634C/C had lower disease­free survival. Patients with the VEGF ­634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ­634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.

A phase II study of the combination of gemcitabine plus carboplatin as the neoadjuvant treatment in locally advanced breast cancer.

OBJECTIVE: Although anthracycline-based regimen is standard neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC), there is some concern over its toxicities such as alopecia and cardiotoxicity. Gemcitabine is another active agent in metastatic breast cancer after failure to anthracycline with less toxicity. The objective of the present study is to evaluate the efficacy and safety of the combination of gemcitabine and carboplatin as NAC in LABC. MATERIAL AND METHOD: Patients with histologically confirmed LABC (T3, T4 or N2 and M0) were included. Patients were scheduled to receive 3 cycles of neoadjuvant GC (gemcitabine 1,000 mg/m2 D1, D8 and carboplatin AUC x 5 D1) every 21 days. Patients with clinical response underwent surgery and additional 3 cycles of adjuvant GC. Primary endpoint was clinical response rate whereas secondary endpoints included pathological response, DFS, OS and toxicity. RESULTS: Between 2004 and 2007, 40 LABC patients were enrolled. Of 40 patients, 35 were evaluable for efficacy and 40 for toxicity. Twenty-three out of 35 patients (65%) obtained cPR. Among 22 patients who had clinical response and who underwent surgery, overall pathological response rate was 51.5% with 1-pCR (2.9%) and 17-pPR (48.5%). All 7 triple-negative patients had pathological response (1-pCR, 6-pPR). At median follow-up of 59 months, median DFS and OS were not reached. Five-year OS and DFS were 67% and 62%, respectively Major adverse effect was myelosuppression without fatal complications. CONCLUSION: The combination GC was feasible and well-tolerated for LABC in neoadjuvant setting. Triple-negative subgroup seems to have high response to GC.

Primary hyperparathyroidism: 11-year experience in a single institute in Thailand.

Primary hyperparathyroidism (PHPT) is not an uncommon disease in the western countries. In Thailand, on the contrary, PHPT was a rare condition with various clinical presentations. All 45 PHPT patients who underwent parathyroidectomy at the Department of Surgery, Siriraj Hospital during January 1997 and December 2007 were retrospectively reviewed. Demographic data, clinical presentation, localizations imaging, operative procedures, findings, complications, and pathological reports were analyzed. Median age was 49 years (range 15-89 years) with female: male ratio of 3 : 1. Only one patient (2.2%) was asymptomatic PHPT. Of all symptomatic cases, 30 (66.7%) had skeletal symptoms, 7 (15.6%) had renal impairment, and 39 (86.7%) had mixed symptoms. 42 patients (93.3%) had parathyroid scan and all had bilateral exploration of the neck. Postoperative hungry bone syndrome was noted in 10 patients (22%). On followup, skeletal and neuropsychiatric symptoms were improved but the renal impairment was remained. The s small number of asymptomatic PHPT in our study may refer to large number of underdiagnosed PHPT in general population. The guideline for screening serum calcium for diagnosis of PHPT in Thai populations will improve the long-term consequence of the disease but will need further information to identify the target group.

Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women.

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2+), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, χ2). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, χ2). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, χ2). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.