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  • 1
    Electronic Resource
    Electronic Resource
    Malignant phyllodes tumours of the breast display increased stromal p53 protein expression (1999)
    Oxford, U.K. and Cambridge, USA : Blackwell Publishing Ltd
    Histopathology 34 (1999), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To determine the variation in p53 protein expression in phyllodes tumours and fibroadenomas of the breast.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsFifteen phyllodes tumours (six malignant, nine benign) and 20 fibroadenomas were examined for p53 expression by immunohistochemistry. Five of the six malignant phyllodes tumours showed moderate or strong p53 positivity at sites of peri-epithelial stromal condensation and atypia. All 20 fibroadenomas, nine benign phyllodes tumours and one malignant phyllodes tumour showed either negativity or focal weak nuclear positivity of scattered stromal cells.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsIncreased p53 immunoreactivity is present in malignant phyllodes tumours in contrast to benign phyllodes tumours and fibroadenomas. Malignant phyllodes tumours display a distinctive pattern of p53 immunostaining which may be of diagnostic value. These findings suggest that p53 protein may be important in the progression of benign to malignant phyllodes tumours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.1999.00666.x
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  • 2
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    {beta}-Catenin Signaling in ErbB2 Mammary Tumorigenesis (2013)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2013-07-17
    Description: Although ERBB2 amplification and overexpression is correlated with poor outcome in breast cancer, the molecular mechanisms underlying the aggressive nature of these tumors has not been fully elucidated. To investigate this further, we have used a transgenic mouse model of ErbB2-driven tumor progression (ErbB2KI model) that recapitulates clinically relevant events, including selective amplification of the core erbB2 amplicon. By comparing the transcriptional profiles of ErbB2KI mammary tumors and human ERBB2-positive breast cancers, we show that ErbB2KI tumors possess molecular features of the basal subtype of ERBB2-positive human breast cancer, including activation of canonical β-catenin signaling. Inhibition of β-catenin–dependent signaling in ErbB2KI-derived tumor cells using RNA interference impaired tumor initiation and metastasis. Furthermore, treatment of ErbB2KI or human ERBB2-overexpressing tumor cells with a selective β-catenin/CBP inhibitor significantly decreased proliferation and ErbB2 expression. Collectively, our data indicate that ERBB2-mediated breast cancer progression requires β-catenin signaling and can be therapeutically targeted by selective β-catenin/CBP inhibitors. Cancer Res; 73(14); 4474–87. ©2013 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 3
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    Therapeutic targets in triple negative breast cancer (2013)
    BMJ Publishing Group
    Details
    Publication Date: 2013-05-24
    Description: Outcomes have improved significantly for many women diagnosed with breast cancer. For the heterogeneous group of tumours lacking expression of the oestrogen, progesterone and HER2 receptors, ‘triple negative’ breast cancers (TNBC), the prognosis overall has remained quite poor. When TNBC recurs, there is often little response to chemotherapy, and there are a few treatment options in this setting. Thus, there is an urgent clinical need to identify new therapeutic targets in order to improve the outlook for these patients. This review highlights the most promising therapeutic targets identified through new sequencing technologies, as well as through studies of apoptosis. We also present mounting evidence that the developmental signalling pathways Wnt/β-catenin, NOTCH and Hedgehog play an important role in the pathogenesis and progression of TNBC with new therapeutic approaches inhibiting these pathways in advanced preclinical studies or early clinical trials.
    Keywords: Breast cancer
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 4
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    The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome (2018)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2018-05-16
    Description: Purpose: Consensus is lacking regarding the androgen receptor (AR) as a prognostic marker in breast cancer. The objectives of this study were to comprehensively review the literature on AR prognostication and determine optimal criteria for AR as an independent predictor of breast cancer survival. Experimental Design: AR positivity was assessed by immunostaining in two clinically validated primary breast cancer cohorts [training cohort, n = 219; validation cohort, n = 418; 77% and 79% estrogen receptor alpha (ERα) positive, respectively]. The optimal AR cut-point was determined by ROC analysis in the training cohort and applied to both cohorts. Results: AR was an independent prognostic marker of breast cancer outcome in 22 of 46 (48%) previous studies that performed multivariate analyses. Most studies used cut-points of 1% or 10% nuclear positivity. Herein, neither 1% nor 10% cut-points were robustly prognostic. ROC analysis revealed that a higher AR cut-point (78% positivity) provided optimal sensitivity and specificity to predict breast cancer survival in the training (HR, 0.41; P = 0.015) and validation (HR, 0.50; P = 0.014) cohorts. Tenfold cross-validation confirmed the robustness of this AR cut-point. Patients with ERα-positive tumors and AR positivity ≥78% had the best survival in both cohorts ( P 〈 0.0001). Among the combined ERα-positive cases, those with comparable or higher levels of AR (AR:ERα-positivity ratio 〉0.87) had the best outcomes ( P 〈 0.0001). Conclusions: This study defines an optimal AR cut-point to reliably predict breast cancer survival. Testing this cut-point in prospective cohorts is warranted for implementation of AR as a prognostic factor in the clinical management of breast cancer. Clin Cancer Res; 24(10); 2328–41. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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