Abstract
The Oncotype Dx assay is frequently used to test if breast cancer patients can be spared from chemotherapy without negative effects for their future clinical course. However, due to conflicting data on the assay utility, in the recent past its reimbursement situation in Germany was revised; due to continued requests by clinicians for predictive values, our group decided to implement an Oncotype Dx like alternative assay with the objective of obtaining quality and cost optimization. Customized RT2-Profiler assays covering the 21 gene panel of the Oncotype Dx assay were applied to a pilot cohort of breast cancer patients with known Oncotype Dx Recurrence Score (RS). The Ct values obtained with RT2-Profiler-assays were used to calculate the unscaled Recurrence Score (RSu) values and the thereon based RS according to the Oncotype DX assay rules if available. Despite consistent assay performance it was impossible to establish correlations between RT2-Profiler recurrence scores with the respective Oncotype DX values not to mention exact matches. By following the Oncotype DX assay and its interpretation as close as possible we faced several obstructions such as lack of information on RNA amount used, missing units in the single gene expression report, missing references cited in the original study that should explain the determination of the recurrence score formula, and vague information on the normalization of the gene expression impeding the reproduction of Oncotype Dx results in other laboratories. Unfortunately, the Oncotype Dx assay cannot be confirmed by the customized RT2-profiler assay, not least because of the fact that the individual gene measurements are not provided in the medical report, although these are mandatory for the RS calculation. In fact, the “single gene report” only contains unscaled scores of the ER, PR, and Her2 genes without any internationally accepted unit used to describe a transcript quantity. Therefore a direct comparison with the in-house measurement to evaluate its performance is impossible. With regard to our findings and the fact that the Oncotype RS represents a likelihood of the risk of relapse it thus remains impossible to assess the clinical necessity of this assay.
Highlights
In 2004 a study published by Paik and coworkers reported the utility of a new prognostic gene expression assay in breast cancer patients[1]
Thereby the standard deviations of the mean were calculated for all individual genes, the group scores and the Recurrence Score (RS) (Fig. 2a), the latter calculated as previously described by Paik et al.[1] (Fig. 2b)
Housekeeping genes (HKGs) are colored in green, genes used to calculate the GRB7 group score are colored in light blue, genes belonging to the invasion www.nature.com/scientificreports group score are colored in blue, genes used for the ER group score are colored in yellow, and genes used to calculate the proliferation group score are colored in orange (Fig. 2)
Summary
In 2004 a study published by Paik and coworkers reported the utility of a new prognostic gene expression assay in breast cancer patients[1]. The authors addressed the question if key experiments from 50 cancer studies published between 2010 and 2012 in so called high impact journals could be replicated. They expected that the two key features of science, reproducibility and transparency, would apply to those studies as these generally accepted key features can be seen as a prerequisite for modern science[2]. In 2017 two authors of the Cancer Biology Reproducibility Study, Nosek and Errington, published the first preliminary results[3] Whilst they concede that “there is no such thing such as exact replication because there are always differences between the original study and the replication”, they claimed that retesting a hypothesis with. The same or a closely related methodology should provide the same evidence enabling the investigators to converge on a general explanation independent of methodology[3]
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