Prognostic & Predictive Testing | Oncotype DX Test

The Oncotype DX Breast Recurrence Score® test is the only test validated as both prognostic of disease outcome and predictive of chemotherapy benefit in HR+, HER2- early invasive breast cancer patients^3-4,9,11. Validation of the Oncotype DX test was conducted according to published standards with a formal test of interaction from a clinical trial where patients were randomized to treatment group^1,4,11. Other multigene assays and clinical-pathologic features have not provided evidence for chemo-prediction.^12-14

A prognostic test estimates a likely disease outcome¹. Examples of disease outcomes in breast cancer are distant recurrence, disease progression or death. For a solely prognostic test, treatment effect does not depend on the test result.¹

A chemo-predictive test predicts the effect of chemotherapy on a disease outcome, identifying patients who are more and less likely to benefit from the treatment.

The Oncotype DX Breast Recurrence Score^® test meets the criteria for a predictive test/biomarker:^{1, 4, 11}

Treatment effect differs for biomarker-positive patients (i.e., high risk by Recurrence Score^® result) compared with biomarker-negative patients (i.e., low risk by Recurrence Score result).

The formal test for an interaction between the biomarker result and treatment group on disease outcome is statistically significant.

The interaction of the biomarker result and treatment group on disease outcome was assessed in data from a clinical trial where patients were randomized to treatment group.

Treatment decisions in early breast cancer have historically been based on prognostic factors alone (grade, size and age). The Oncotype DX test adds information to help guide chemotherapy decisions.

A test predictive of chemotherapy benefit, which provides additional information on prognosis, can help avoid over- and under treatment with chemotherapy.^{4, 11, 15}.

Multigene assays are not interchangeable; studies show high rates of discordance across all multigene assays (>40% discordance rate)². Other multigene assays analysing different genes were developed to estimate disease prognosis only; hence, such variability would be expected when compared to the Oncotype DX test, the only assay proven to predict chemotherapy benefit.^4,11 Similarly, substantial discordance has been observed between prognostic-only parameters (e.g. tumour grade, Ki67 level and nodal status) and the Oncotype DX test^4,16; only the Oncotype DX test has been validated for the purpose of identifying patients who may benefit from chemotherapy and those who may not, rather than extrapolating that benefit from a prognostic-only parameter.^{13, 14}

While all four multigene assays provide prognostic information, only the Oncotype DX Breast Recurrence Score assay can identify patients who will benefit and those who can be spared chemotherapy.^4,11

Abbreviations

BCI=Breast Cancer Index
CT=chemotherapy
ER=estrogene receptor
ET=endocrine therapy
HER2–=human epidermal growth factor receptor 2 negative
HR+=hormone receptor positive
MMP= MammaPrint
N+=node positive
RCT=randomised clinical trial
RS=Recurrence Score result

References

Ballman et al. J Clin Oncol. 2015.
Varga et al. ESMO. 2017.
Paik et al. N Engl J Med. 2004.
Paik et al. J Clin Oncol. 2006.
Filipits et al. Clin Cancer Res. 2011.
Bueno-de-Mesquita et al. Lancet Oncol. 2007.
Cardoso et al. New Eng J. Med. 2016.
Dowsett et al. J Clin Oncol. 2013.
Gnant et al. Ann Oncol. 2014.
Albain et al. Lancet Oncol. 2010.
Markopoulos Eur J Durg Oncol 2017.
Hyams J Surg Oncol 2017.
Markopoulos Eur J Surg Oncol 2019.
Sparano JA et al. N Engl J Med. 2018.
Nitz et al. J Clin Oncol. 2019.

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Prognostic vs. predictive test

Abbreviations

References