Article

Molecular evolution of breat cancer

The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
The Journal of Pathology (Impact Factor: 7.43). 01/2005; 205(2):248-54. DOI: 10.1002/path.1691
Source: PubMed

ABSTRACT Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.

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    • "Breast cancer (BC) is the most common cancer and the second most common cause of mortality in women due to cancer (Siegel et al., 2011). It is a heterogeneous disease that encompasses a variety of clinical patterns, biological behaviors, prognostic characteristics, and responses to different types of treatment (Simpson et al., 2005). Ambitious efforts have been made to improve overall survival (OS) and morbidity by early diagnosis and multiple therapies (Curigliano et al., 2007). "
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    ABSTRACT: Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.
    Asian Pacific journal of cancer prevention: APJCP 12/2013; 14(12):7645-9. DOI:10.7314/APJCP.2013.14.12.7645 · 2.51 Impact Factor
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    • "Breast cancer is a heterogeneous disease comprising subtypes of varied morphology, prognostic profiles, and clinical outcomes [1] [2]. Tumours arise from malignant transformation of hyperplasic epithelia within the breast [3], and numerous mutagenic changes contribute to the transformation process which abnormally alters the cellular environment. "
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    ABSTRACT: Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. "Individualised" strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.
    International Journal of Cell Biology 07/2013; 2013(5994):973584. DOI:10.1155/2013/973584
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    • "Taking advantage from the only microarray dataset publicly accessible at the ArrayExpress web site, we investigated the pattern of expression of a selected panel of genes involved in TGF-β-mediated EMT or associated with epithelial cells identity (i.e., cell polarity and apical junction complex) and cell-fate decision in a series of DCIS and corresponding patient-matched histologically normal (HN) epithelium [11]. As the whole-gene expression profile of patient-matched atypical ductal hyperplasia (ADH) was also available, we further compared DCIS and ADH profiles to verify the hypothesis according to which breast cancer progression is a multistep process involving a continuum of changes from normal phenotype through hyperplastic lesions, carcinoma in situ, and invasive carcinoma [21] "
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    ABSTRACT: Loss of epithelial cell identity and acquisition of mesenchymal features are early events in the neoplastic transformation of mammary cells. We investigated the pattern of expression of a selected panel of genes associated with cell polarity and apical junction complex or involved in TGF-β-mediated epithelial-mesenchymal transition and cell-fate decision in a series of DCIS and corresponding patient-matched normal tissue. Additionally, we compared DCIS gene profile with that of atypical ductal hyperplasia (ADH) from the same patient. Statistical analysis identified a "core" of genes differentially expressed in both precursors with respect to the corresponding normal tissue mainly associated with a terminally differentiated luminal estrogen-dependent phenotype, in agreement with the model according to which ER-positive invasive breast cancer derives from ER-positive progenitor cells, and with an autocrine production of estrogens through androgens conversion. Although preliminary, present findings provide transcriptomic confirmation that, at least for the panel of genes considered in present study, ADH and DCIS are part of a tumorigenic multistep process and strongly arise the necessity for the regulation, maybe using aromatase inhibitors, of the intratumoral and/or circulating concentration of biologically active androgens in DCIS patients to timely hamper abnormal estrogens production and block estrogen-induced cell proliferation.
    04/2012; 2012:984346. DOI:10.1155/2012/984346
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