1971 A correlative study of Ki67 and two multigene RNA expression signatures in operable ER-positive postmenopausal breast cancer (SAKK 26/10)

Jaggi, Rolf; Varga, Zsuzsanna; Bigler, Martin; Bize, Vincent; Eduardo, Mariana Bustamante; Berardi, Simona; Chiesa, Flaminia; Dedes, Konstantine J.; Müller, A; Tausch, Christoph; Vetter, Marcus; Moos, Roger von; Winterhalder, Ralph; Zimmermann, S; Pestalozzi, BC; Aebi, Stefan

doi:10.1016/s0959-8049(16)30919-4

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“…We directly compared RISK with RS that was either measured at Genomic Health, or in our own laboratory, and we found higher correlations when RS was measured on the same tissue and in the same laboratory (ρ = 0.82, κ = 0.52 as compared to ρ = 0.43, κ = 0.23). The comparison was based on 220 prospectively collected samples (data not shown and [38]).…”

Section: Discussionmentioning

confidence: 99%

Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases

et al. 2019

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Background Breast cancer is a leading cause of cancer-related death in women worldwide. Despite extensive studies in all areas of basic, clinical and applied research, accurate prognosis remains elusive, thus leading to overtreatment of many patients. Diagnosis could be improved by introducing multigene molecular scores in standard clinical practice. Several tests that work with formalin-fixed tissue have become routine. Molecular scores usually include several genes representing processes, response to oestrogens, progestogens and human epidermal growth factor receptor 2 (Her2), respectively, which are combined additively in single values. These multi-gene scores have the advantage of being more robust and reproducible than single-gene scores. Their utility may be further enhanced by combining them with classical diagnostic parameters. Here, we present an exploratory study comparing the RISK and research versions of Oncotype DX recurrence score (RS), Prosigna Risk of Recurrence (ROR) and EndoPredict (EP) with respect to their prognostic potential for ipsilateral recurrence and/or distant relapse in brain, and we compared the scores to the intrinsic subtypes based on PAM50. Methods RNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue cores of primary tumours, local recurrences and brain metastases. Gene expression was measured on a NanoString nCounter Analysis System. Intrinsic subtypes and molecular scores were computed according to published literature and RISK, RS, ROR and EP were compared against each other and to the intrinsic subtypes Luminal A (lumA), Luminal B (lumB), Her2-enriched (Her2↑), Basal-like (basal), and Normal-like (normal) of PAM50. Local recurrences and brain metastases were compared to their corresponding primary tumours. Results All four molecular scores were highly correlated. Highest correlations were observed among genes related to proliferation while lower correlations were found among oestrogen-related genes. The scores were significantly higher in primary tumours progressing to brain metastases as compared to recurrence-free primary tumours and primary tumours that relapsed as local recurrences. Conclusions RISK and ROR-P are prognostic for primary tumours metastasizing to the brain. All four scores, RISK, RS, EP and ROR-P failed to discriminate between primary tumours that remained recurrence-free and primary tumours relapsing as local recurrences. Electronic supplementary material The online version of this article (10.1186/s12885-019-5752-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%