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1.
J Cancer Res Clin Oncol ; 136(12): 1915-20, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20213094

ABSTRACT

Bladder cancer, in its advanced stage, has very few therapeutic strategies with proven efficacy. Platinum-combination chemotherapy can be considered a standard for first-line therapy, but after progression there is no standard therapy, and the prognosis is very poor. The development of targeted therapies in the last few years has significantly changed the prognosis of a wide variety of tumors. In bladder cancer, there is no targeted therapy currently approved for its use in advanced disease. There is evidence that Her-2 amplification and/or overexpression is seen in bladder cancer, and may influence prognosis. Anti-Her-2 drugs, such as trastuzumab or lapatinib, are under investigation in urothelial neoplasms, but there is no phase III trial that has evaluated their use in bladder cancer. We review the published evidence about Her-2 determination, its influence on bladder carcinoma prognosis, the clinical development of anti-Her-2-targeted therapies, and the possible future research directions involving this pathway in bladder cancer.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Quinazolines/therapeutic use , Receptor, ErbB-2/antagonists & inhibitors , Urinary Bladder Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Gene Expression Regulation, Neoplastic , Humans , Lapatinib , Models, Biological , Prognosis , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Signal Transduction/drug effects , Trastuzumab , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism
2.
South Med J ; 102(9): 929-34, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19668023

ABSTRACT

Complaints of loss of memory and lack of concentration have been reported by long-term survivors of breast cancer. This mild cognitive impairment (MCI), also called "chemobrain" or "chemofog," has been the subject of a number of studies in the last few years. This cognitive impairment, although usually mild, must be studied to define possible risk factors for its development, and for future research into a preventive or therapeutic treatment approach. Long-term survivors of breast cancer must be followed to detect possible treatment sequelae as soon as possible. Since the number of these long-term survivors has increased in the last years, in part because of more active adjuvant treatments, our knowledge about the long-term side effects of these therapies has also grown.


Subject(s)
Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant/adverse effects , Cognition Disorders/chemically induced , Breast Neoplasms/psychology , Cognition Disorders/diagnosis , Depression/complications , Fatigue/complications , Fatigue/etiology , Female , Humans , Neuropsychological Tests , Survivors
3.
PLoS One ; 4(6): e5911, 2009 Jun 15.
Article in English | MEDLINE | ID: mdl-19547727

ABSTRACT

INTRODUCTION: Gene profiling may improve prognostic accuracy in patients with early breast cancer, but this technology is not widely available. We used commercial assays for qRT-PCR to assess the performance of the gene profiles included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio. METHODS: 153 patients with early breast cancer and a minimum follow-up of 5 years were included. All tumours were positive for hormonal receptors and 38% had positive lymph nodes; 64% of patients received adjuvant chemotherapy. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) specimens using a specific kit. qRT-PCR amplifications were performed with TaqMan Gene Expression Assays products. We applied the three gene-expression-based models to our patient cohort to compare the predictions derived from these gene sets. RESULTS: After a median follow-up of 91 months, 22% of patients relapsed. The distant metastasis-free survival (DMFS) at 5 years was calculated for each profile. For the 70-Gene Signature, DMFS was 95% -good prognosis- versus 66% -poor prognosis. In the case of the Recurrence Score, DMFS was 98%, 81% and 69% for low, intermediate and high-risk groups, respectively. Finally, for the Two-Gene Ratio, DMFS was 86% versus 70%. The 70-Gene Signature and the Recurrence Score were highly informative in identifying patients with distant metastasis, even in multivariate analysis. CONCLUSION: Commercially available assays for qRT-PCR can be used to assess the prognostic utility of previously published gene expression profiles in FFPE material from patients with early breast cancer. Our results, with the use of a different platform and with different material, confirm the robustness of the 70-Gene Signature and represent an independent test for the Recurrence Score, using different primer/probe sets.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Gene Expression Profiling , Reverse Transcriptase Polymerase Chain Reaction/methods , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Middle Aged , Prognosis , Recurrence , Reproducibility of Results , Retrospective Studies
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