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ABSTRACT: To evaluate the efficacy of etoposide, cisplatin-etoposide, methotrexate, actinomycin-D (EP-EMA) chemotherapy as the frontline treatment for gestational trophoblastic neoplasia (GTN) patients with very high (≥ 12) FIGO prognostic scores.
Nine patients with very-high-risk GTN were treated with EP-EMA at the Cancer Institute, Adyar, India, between January 1, 2001, and December 31, 2007. Salvage chemotherapy, adjuvant surgery, and radiotherapy were used when indicated. Clinical response, toxicity, and survival were analyzed separately.
The median FIGO score was 15. Six (66.7%) patients had a complete clinical response, whereas progressive disease occurred for 3 (33.3%) women. None of the patients relapsed. This translated to an overall survival rate of 66.7% in the primary setting. All patients with liver-only metastases were survivors after treatment with EP-EMA. Grade 3 neutropenia was detected in 3 (33.3%) patients only. No life-threatening toxicity was observed after EP-EMA treatment.
EP-EMA was highly effective for the primary management of very-high-risk GTN.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 07/2011; 115(1):37-9. · 1.41 Impact Factor
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ABSTRACT: Breast cancer incidence has been on the increase in south Indian women. Polymorphisms in DNA repair genes modify an individual's risk to cancer. XPD (Xeroderma pigmentosum D), a DNA helicase gene involved in nucleotide excision repair and transcription coupled repair, may affect an individual's DNA repair capacity, particularly that of bulky adducts. This case-control study (250 breast cancer cases and 500 healthy controls) aimed to investigate the role of the XPD Lys751Gln polymorphism as a risk factor in the development of breast cancer. Genotyping was performed using the Taq Man allelic discrimination assay. Immunohisto-chemistry was used to quantitate the level of polycyclic aromatic hydrocarbon (PAH) adducts in biopsy samples obtained from the breast cancer patients. Results showed that the XPD Gln/Gln genotype was significantly associated with an increased risk of breast cancer (OR, 1.75; 95% CI 1.02-2.80), particularly in premenopausal female patients (OR, 2.6; 95% CI 1.33-4.79). PAH adduct levels were significantly higher in the cases with breast cancer as compared to the normal breast tissue. This study reveals that XPD may play a role in increasing breast cancer risk particularly in premenopausal females.
Oncology letters 01/2011; 2(1):155-159. · 0.11 Impact Factor
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ABSTRACT: Hereditary cancers account for 5-10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases.
PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test.
Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53).
The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers.
Hereditary Cancer in Clinical Practice 08/2009; 7(1):13. · 1.68 Impact Factor
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ABSTRACT: The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.
Breast Cancer Research and Treatment 01/2008; 112(1):81-7. · 4.43 Impact Factor
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ABSTRACT: Cancer of the breast is the second most common cancer seen among Indian women. This study describes the use of DHPLC for mutation analysis for BRCA1, BRCA2 and CHEK2 (1100delC) in 22 patients with a family history of breast and/or ovarian cancer and early onset breast cancer (<35 years of age). Three of the 22 patients were found to have a non-sense mutation or a deletion, resulting in a premature stop codon, potentially leading to a truncated protein. Two of these were in BRCA1 (one was a novel 5 base deletion) and one in the BRCA2 gene. No patient was found in our series to have the CHEK2 (1100delC) mutation. DNA from a healthy blood donor and all but one of the 22 patients, demonstrated polymorphisms in BRCA1 and/or BRCA2 genes. This is the first study from South India, on BRCA1, BRCA2 & CHEK2 (1100 del C) mutations in patients with a family history of breast and/or ovarian cancer and early onset breast/ovarian cancer, using the sensitive DHPLC approach.
Asian Pacific journal of cancer prevention: APJCP 4(3):203-8. · 0.66 Impact Factor
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ABSTRACT: The present study was undertaken to examine the frequencies of GSTM1 (Null/Present), GSTP1 (Ile105Val) and p53 (Arg72Pro) genotypes and their relations to breast cancer susceptibility in South Indian women. This case - control study involved 250 consecutive breast cancer cases and 500 healthy controls matched in five-year age categories in the ratio of 1:2. Genotyping was performed by PCR for GSTM1, Real-Time Allelic discrimination assay for GSTP1 and PCR-CTPP for p53. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for the known risk factors for breast cancer. The frequencies for the GSTM1 Null genotype were 26% in the cases and 22% in the controls; for GSTP1 Ile/Ile, Ile/Val, Val/Val the frequencies were 46.6%, 41.9% and 11.5%, respectively, in cases and 46.0%, 43.8% and 10.2% in controls; for p53 Arg/Arg, Arg/Pro & Pro/Pro the frequencies were 26.4%, 50.0% and 23.6% in cases and 27.0%, 44.8% and 28.2% in controls. A nonsignificant elevation in breast cancer risk was observed among women who had the GSTM1 Null genotype (OR=1.24; 95% CI=0.83-1.84), the p53 Arg/Arg genotype (OR=1.28; 95% CI=0.81-2.03) and the Pro/Arg genotype (OR=1.49; 95% CI=0.99-2.25), and the GSTP1 Val/Val genotype (OR=1.1; 95% CI=0.64-1.91).
Asian Pacific journal of cancer prevention: APJCP 8(2):253-7. · 0.66 Impact Factor
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ABSTRACT: To evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia (GTN).
Thirty-five patients with high-risk GTN were treated with 196 cycles of EMA-CO between 1997 and 2006. Twenty-nine patients received EMA-CO in the primary setting and another 6 after failure of single-agent chemotherapy. Salvage chemotherapy was offered to selected patients.
Of the 29 patients treated with EMA-CO in the primary setting, 22 (75.8%) had a complete clinical response, 5 (17.1%) progressed, and 2 (7.1%) had early deaths. Three patients relapsed after achieving initial complete response. Five were treated with salvage chemotherapy, of which only 2 survived. This translated to overall survival rate of 71% in the primary setting. Five of the 6 patients treated with EMA-CO as second line are survivors. Life threatening toxicity was not seen after EMA-CO. Nine subsequent normal pregnancies were reported after EMA-CO.
EMA-CO was highly effective for the management of high-risk GTN, and the toxicities were minimal. Reproductive outcome after treatment with EMA-CO was excellent.
The Journal of reproductive medicine 56(5-6):219-23. · 0.87 Impact Factor
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ABSTRACT: Breast cancer is initiated by exposure to endogenous and exogenous estrogens. A case-control (n= 250-500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in CYP17 (T34C), CYP19 (Trp39Arg) and FGFR2(C906T). Genotyping was done using the Taqman allelic discrimination assay for CYP17 (T34C) and FGFR2 (T906C) and PCR-CTPP for CYP19 (Trp39Arg). There was a significant protective association of the (TT/CC) genotype of the CYP17 gene against the risk of developing breast cancer (OR= 0.68, 95% CI: 0.49-0.96), which was more significant in postmenopausal women (OR= 0.56, 95% CI: 0.35-0.89) (p= 0.015). CYP19 (Trp39Arg) is a rare polymorphism and all the cases were homozygous for the wild type Trp allele (100%); this was also the case for 99.2% of the controls. We were unable to detect any variant form of the CYP19 gene in south Indian women. There was no significant association between the risk of breast cancer and FGFR2 (C906T). These results suggest that the CYP17 TT/CC genotype is associated with decreased risk for breast cancer, especially in post menopausal women.
Asian Pacific journal of cancer prevention: APJCP 10(1):111-4. · 0.66 Impact Factor
