Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre

Abstract

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Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer

“…In recent times, there has been a critical vogue surrounding the degree of discordance between pathological parameters such as nuclear grade and Ki-67 indices alone/in isolation [121][122][123][124][125], rendering RS testing favourable in aiding prognosis, in spite of its limitations [126]. Therefore, it is somewhat unsurprising that the data from several studies highlight the correlative nature of RS and Ki-67 protein expression in Luminal breast cancer (p < 0.001) [114,127,128], particularly in cancers with high Ki-67 expression. In MammaPrint ® (Agendia, Amsterdam, The Netherlands), a 70gene panel boasting comprehensive measurement of the six hallmarks of cancer-related molecular biology [129], their 70 genes were selected from genome-wide expression data using a data-driven approach in an unbiased fashion; there were no predefined assumptions as to whether certain genes were more likely to increase the risk of distant recurrence development in patients with early-stage breast cancer [130].…”

OncotypeDX© Recurrence Score in BRCA mutation carriers: a systematic review and meta-analysis

“…This suggests the possibility of an increased penetrance of potentially undiagnosed BRCA mutations in patients with ERþ/HER2À tumours, which subsequently will be stratified to be RS > 30 following genomic testing after cancer diagnosis. Overall, the total patient cohort included in this study represent a typical distribution of expected RS for patients diagnosed with early-stage ERþ disease [14,15,41], providing a fair representation of anticipated scores for this cohort. This poses the question as to how these results may be clinically extrapolated into the population, as to ensure patients may be better served in prospective practice: Perhaps the expansion of indications for routine genetic screening of this cohort for breast cancer susceptibility may be warranted, with the aforementioned criteria (i.e., ERþ/HER2À breast cancers with RS > 30) being incorporated into novel indications for genetic testing in order to capture the 10% with potentially underlying genetic mutations.…”

“…The molecular era has facilitated the development of multigene panels to aid prognostication and therapeutic decision making for patients diagnosed with early-stage luminal breast cancer [13]. OncotypeDXª Recurrence Score (RS) (Genomic Health Inc., Redwood City, CA) is a clinically validated 21-gene signature used to select patients with early ERþ, human epidermal growth factor receptor-2 negative (HER2À) breast cancer who are perceived to derive the most benefit from cytotoxic chemotherapy prescription [14,15]. RS proves useful in detecting the large proportion of early-stage ERþ cancers gaining minimal benefit from chemotherapeutic agents [16].…”

The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment

“…Despite considerable funding, investment and resource distribution into the investigation of miRNA as reliable and reproducible clinical biomarkers in breast cancer research and treatment, we are yet to undercover novel biomarkers which can rival the principal ER, PgR, and HER2 receptors to inform breast cancer diagnosis, prognosis and therapeutic strategies. Since the emergence of the molecular era, genomic signatures such as the 21-gene assay and the Mammaprint© 70-gene assay (Agendia, Amsterdam, The Netherlands) has reliably and reproducibly informed prognoses, refined therapeutic systematic chemotherapy prescription and facilitated personalised cancer treatment in early-stage luminal diseases [ 84 , 85 , 86 , 87 , 88 ]. The identification and characterisation of miRNA expression which are as reliable and reproducible as these genomic panels limit current hypotheses, suggesting miRNAs may be impactful biomarkers in malignancy [ 89 ].…”