MammaPrint versus EndoPredict: Poor correlation in disease recurrence risk classification of hormone receptor positive breast cancer

Abstract

IntroductionCorrect risk assessment of disease recurrence in patients with early breast cancer is critically important to detect patients who may be spared adjuvant chemotherapy. In clinical practice this is increasingly done based on the results of gene expression assays. In the present study we compared the concordance of the 70-gene signature MammaPrint (MP) with the 12 gene assay EndoPredict (EP).MethodsRepresentative tissue of 48 primary tumours was analysed with the MP during routine diagnostic purposes. Corresponding formalin-fixed, paraffin-embedded tissue was thereafter analysed by the EP test. Risk categories of both tests were compared.Results41 of 48 tumours could be directly compared by both tests. Of the 17 MP low risk cases, only 9 were considered low risk by EP (53% agreement) and of the 24 MP high risk cases, 18 were high risk by EP (75% agreement). Discrepancies occurred in 14 of 41 cases (34.1%). There was only a weak and non-significant correlation between the MP and EP test with an overall concordance of only 66%. The original therapeutic recommendation was based on the MP and would have been changed in 38% of the patients following EP test results. 4 patients developed distant metastases. The respective tumours of these patients were all classified as high risk by the EP, but only 3 were classified as high risk by the MP.ConclusionBoth tests resulted in different treatment recommendations for a significant proportion of patients and cannot be used interchangeably. The results underscore the urgent need for further comparative analyses of multi-genomic tests to avoid misclassification of disease recurrence risk in breast cancer patients.

Summary of head‐to‐head comparisons of patient risk classifications by the 21‐gene Recurrence Score® (RS) assay and other genomic assays for early breast cancer

“…An emerging number of papers have addressed the impact of multigene tests on adjuvant chemotherapy decisions by physicians. A recently published paper comparing MammaPrint and EndoPredict risk stratification showed a poor correlation between the two tests and noted that following EndoPredict results in the study, a change in therapy decisions in favor of adding chemotherapy to hormone therapy would have occurred in 38% of the patients . Another recent study by the SAKK 26/10 analyzed the decision impact of Oncotype DX testing and reported a change in therapy decision against chemotherapy and in favor of hormone therapy alone in 44% of the patients .…”

“…A recently published paper comparing MammaPrint and EndoPredict risk stratification showed a poor correlation between the two tests and noted that following EndoPredict results in the study, a change in therapy decisions in favor of adding chemotherapy to hormone therapy would have occurred in 38% of the patients. 56 Another recent study by the SAKK 26/10 analyzed the decision impact of Oncotype DX testing and reported a change in therapy decision against chemotherapy and in favor of hormone therapy alone in 44% of the patients. 57 A similar recent UK study reported a change against chemotherapy in favor of endocrine therapy alone in 69.2% of patients after the Oncotype DX results were discussed in an interdisciplinary meeting.…”

SHON expression predicts response and relapse risk of breast cancer patients after anthracycline-based combination chemotherapy or tamoxifen treatment

“… 30 This is because these gene-expression biomarkers share common molecular pathways centred on cell proliferation and cell cycle regulation, which are the key components of the well-established pathological parameters. 30 Moreover, MammaPrint and EndoPredic have been found to give different treatment recommendations for a portion of patients and cannot be used interchangeably, 31 while Oncotype DX and MammaPrint offer different prognostic information to the same patients. 32 Another issue with multigene tests is that some patients will still have an “intermediate” risk score, leading to an inconclusive prognosis, 26 though chemotherapy may be surely spared in patients at intermediate recurrence scores as shown in the recent prospective TAILORx trail.…”

Network and Systems Medicine: Position Paper of the European Collaboration on Science and Technology Action on Open Multiscale Systems Medicine

“…However, recent results raise concerns regarding their predictive clinical value. 58 , 59 The major problem is the selection of biomarkers due to the small number of samples compared with a very high number of features. The Cancer Genome Atlas 60 and the International Cancer Genome Consortium data portal 61 are, by far, the most comprehensive repositories for clinical cancer omics data worldwide.…”