Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways

Eroles, Pîlar; Bosch, Ana; Fidalgo, José Alejandro Pérez; Lluch, Aña

doi:10.1016/j.ctrv.2011.11.005

Cited by 492 publications

(446 citation statements)

References 82 publications

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“…Of the 1038 remaining individuals, 885 had molecular subtype assignments available. Samples classified as 'Normal-like subtype' (n = 105) were excluded as the clinical relevance for this subtype has been questioned, 35 leaving 780 samples for further analysis. To reduce any potential batch differences between our and the 'Cancer Genome Atlas' data sets, the two data sets were preprocessed using the same bioinformatic pipeline and variables were mean centered and scaled to unit variance.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Digital image analysis outperforms manual biomarker assessment in breast cancer

Stålhammar

Martínez

Lippert³

et al. 2016

Modern Pathology

153

128

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In the spectrum of breast cancers, categorization according to the four gene expression-based subtypes 'Luminal A,' 'Luminal B,' 'HER2-enriched,' and 'Basal-like' is the method of choice for prognostic and predictive value. As gene expression assays are not yet universally available, routine immunohistochemical stains act as surrogate markers for these subtypes. Thus, congruence of surrogate markers and gene expression tests is of utmost importance. In this study, 3 cohorts of primary breast cancer specimens (total n = 436) with up to 28 years of survival data were scored for Ki67, ER, PR, and HER2 status manually and by digital image analysis (DIA). The results were then compared for sensitivity and specificity for the Luminal B subtype, concordance to PAM50 assays in subtype classification and prognostic power. The DIA system used was the Visiopharm Integrator System. DIA outperformed manual scoring in terms of sensitivity and specificity for the Luminal B subtype, widely considered the most challenging distinction in surrogate subclassification, and produced slightly better concordance and Cohen's κ agreement with PAM50 gene expression assays. Manual biomarker scores and DIA essentially matched each other for Cox regression hazard ratios for all-cause mortality. When the Nottingham combined histologic grade (Elston-Ellis) was used as a prognostic surrogate, stronger Spearman's rank-order correlations were produced by DIA. Prognostic value of Ki67 scores in terms of likelihood ratio χ 2 (LR χ 2 ) was higher for DIA that also added significantly more prognostic information to the manual scores (LR− Δχ 2 ). In conclusion, the system for DIA evaluated here was in most aspects a superior alternative to manual biomarker scoring. It also has the potential to reduce time consumption for pathologists, as many of the steps in the workflow are either automatic or feasible to manage without pathological expertise.

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Section: Immunohistochemistrymentioning

confidence: 99%

Digital image analysis outperforms manual biomarker assessment in breast cancer

Stålhammar

Martínez

Lippert³

et al. 2016

Modern Pathology

153

128

View full text Add to dashboard Cite

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“…It can be classified into several distinct subtypes according to different parameters such as histological grade, tumor size, lymph node involvement, receptor status, or affected signaling pathways (12). Basal-like breast cancers frequently lack expression of the estrogen, progesterone, and HER2/ErbB receptors, and these cancers are referred to as triple negative.…”

Section: Protein Kinase D (Pkd)mentioning

confidence: 99%

Elevated Protein Kinase D3 (PKD3) Expression Supports Proliferation of Triple-negative Breast Cancer Cells and Contributes to mTORC1-S6K1 Pathway Activation

Huck

Duss

Haußer

et al. 2014

Journal of Biological Chemistry

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“…P-53 mutation and cell proliferation rate in breast cancer are important markers for poor prognostic prediction. Luminal A subtype cancers also had lower recurency rate (27.8%) and higher survival rate (median survival rate: 2.2 years) in compare to non luminal cancers (Eroles et al, 2012;Guarneri et al, 2009). A study in Chinese cancer women found that luminal A subtype had the highest locoregional relaps -free survival (93.2%), distant metastasis-free survival (91.5%) and disease free survival rates (87.5%) at 5 years, while Her-2+ subtypes showed the highest rate reccurence (27.5%) and locoregional recurrence (11.4%) (Jia et al, 2014).…”

Section: P=0129mentioning

confidence: 99%