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Jerzak K.J.,University of Toronto | Cockburn J.,Juravinski Cancer Center | Pond G.R.,Juravinski Cancer Center | Pritchard K.I.,University of Toronto | And 5 more authors.
Breast Cancer Research and Treatment | Year: 2014

We determined the expression of two transcriptional variants of thyroid hormone receptor alpha (THRα1 and THRα2) in samples from a cohort of breast cancer patients and correlated expression levels with survival. 130 women who were diagnosed with invasive breast carcinoma between 2007 and 2008 were included. Representative sections of their tumours were analyzed in triplicate on a tissue microarray for expression of THRα1 and THRα2 by immunohistochemistry. The prognostic significance of THRα1 and THRα2 expression was assessed using Kaplan–Meier survival analyses, adjusted for known prognostic factors. Seventy-four percent of tumours had high expression of THRα1 (Allred score ≥6) and 40 % had high expression of THRα2. Expression of THRα2 correlated positively with ER expression (p < 0.001) and with PR expression (p < 0.001), but negatively with HER2 expression (p = 0.018). Patients with low THRα2 expression had inferior 5-year overall survival (75.3 %) compared to those with high expression (91.7 %; p = 0.06). In a multivariate model, high THRα2 expression was a significant and independent prognosticator of improved overall survival (HR = 0.84; 95 % CI 0.71–0.98). Many breast tumours express THRα2 at high levels and these patients experience improved survival. Thyroid hormone signalling may be important in a proportion of breast cancers and THRα2 expression may be a regulator of signalling in this pathway. © 2014, Springer Science+Business Media New York. Source

Rafatpanah H.,Mashhad University of Medical Sciences | Rezaee A.,Mashhad University of Medical Sciences | Etemadi M.M.,Mashhad University of Medical Sciences | Hosseini R.F.,Mashhad University of Medical Sciences | And 12 more authors.
Journal of Neuroimmunology | Year: 2012

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory myelopathy. The pathophysiology of HAM/TSP is not yet fully understood; therefore, effective therapy remains a challenging issue. This study was designed to evaluate the efficacy of interferon-alpha (IFN-α) in HAM/TSP patients in the Northeast of Iran. Forty-nine patients with a definite diagnosis of HAM/TSP were enrolled in this clinical trial. For six months, the patients received three million international units of subcutaneous IFN-α-2b per each injection. The dose regimen was daily injection for the first month, three times administration per week for the months 2 and 3, twice weekly injection for the months 4 and 5 and weekly injection for the sixth month. The clinical and laboratory responses were evaluated based on neurologic examinations and immunovirological markers. IFN-α had significant but temporary effect on the motor and urinary functions of the patients. Comparing to the baseline values, proviral load was significantly decreased one month after treatment in responders (495.20 ± 306.87 to 262.69 ± 219.24 p = 0.02) and non-responders (624.86 ± 261.90 to 428.28 ± 259.88 p = 0.03). Anti-HTLV-1 antibody titers were significantly decreased among responders (1152.1 ± 200.5 to 511.6 ± 98.2 p = 0.009) and non-responders (1280.1 ± 368.1 to 537.6 ± 187 p = 0.007). Flow cytometry showed no significant changes in CD4, CD8, CD4CD25 and CD16CD56 counts with IFN-α. The positive impact of IFN-α was observed during the treatment period with significant effects on some clinical aspects of HAM/TSP. © 2012 Elsevier B.V. Source

Wong-Brown M.W.,Hunter Medical Research Institute | Meldrum C.J.,Pathology North | Carpenter J.E.,University of Sydney | Clarke C.L.,University of Sydney | And 5 more authors.
Breast Cancer Research and Treatment | Year: 2015

Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon–intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines. © 2015, Springer Science+Business Media New York. Source

Shai A.,Lin and Carmel Medical Centers | Segev Y.,Familial Breast Cancer Research Unit | Narod S.A.,Familial Breast Cancer Research Unit
Familial Cancer | Year: 2014

Women who report a history of endometrial cancer in a first-degree relative are at increased risk of endometrial cancer, with a hazard ratio of 1.5 to 2.0. Only a minority of patients with familial endometrial cancer have a recognized cancer syndrome. Lynch syndrome is the most common genetic syndrome associated with endometrial cancer and a marked increased risk of colon cancer. Cowden syndrome is a rare condition resulting from a mutation in the tumor suppressor gene phosphatase and tensin homolog. The risk for endometrial cancer is about five times higher in women with Cowden syndrome than in the general population. Recently, a novel germline mutation in the POLD1 gene that encodes the catalytic subunit of DNA polymerase δ was described in several families with multiple cases of endometrial cancer. This mutation is also associated with colorectal cancer. The association between BRCA1 mutations and endometrial cancer has been investigated in several studies; it appears that the risk of endometrial cancer is restricted to women with a history of tamoxifen exposure. In recent years, research has focused on genetic polymorphisms that are associated with endometrial cancer risk. Although many polymorphisms have been identified, their clinical significance is unclear and they have not been adapted for clinical practice. © 2014 Springer Science+Business Media Dordrecht. Source

Giannakeas V.,University of Toronto | Giannakeas V.,Familial Breast Cancer Research Unit | Lubinski J.,Pomeranian Medical University | Gronwald J.,Pomeranian Medical University | And 13 more authors.
Breast Cancer Research and Treatment | Year: 2014

Women with a genetic predisposition to breast cancer may be at increased risk of cancer after exposure to ionizing radiation. It is unclear whether mammography screening increases the risk of breast cancer among BRCA1 and BRCA2 carriers. We identified 2,346 women with a BRCA1 (n = 1844) or BRCA2 (n = 502) mutation and no breast cancer, and we reviewed their history of mammography exposure. These women were followed for an average of 5.3 years and were observed for new breast cancer diagnoses. At study entry, 1808 women (77.1 %) reported ever having had a mammogram; of these, 204 women (11.2 %) reported having had a mammogram before age 30. We estimated the hazard ratios for the development of invasive breast cancer, conditional on the number of prior mammograms and on the age at first mammogram. Hazard ratios were estimated and stratified by gene (BRCA1 or BRCA2), relative to women with no exposure. We observed no significant association between prior mammography exposure and breast cancer risk for BRCA1 carriers (HR 0.79; 95 % CI 0.53-1.19; P = 0.26) or for BRCA2 carriers (HR 0.90; 95 % CI 0.35-2.34; P = 0.83). An early age at first mammogram (<30 years) did not increase breast cancer risk among BRCA1 carriers (HR 0.75; 95 % CI 0.41-1.37; P = 0.35) or among BRCA2 carriers (HR 0.69; 95 % CI 0.19-2.48; P = 0.57). Exposure to mammography in women with BRCA1 and BRCA2 mutations is not associated with an increased risk of breast cancer. © 2014 Springer Science+Business Media. Source

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