Predictive or prognostic test: why does it matter?

What is a prognostic test?

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

What is a predictive test?

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.

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.

Only multi-gene assay can inform about treatment benefit for an individual patient^{1, 4, 11}

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}

How does the Oncotype DX test compare to prognostic-only tests?

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 test4,16; 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}

The Oncotype DX Breast Recurrence Score assay vs. Other multigene assays: 40%–60% discordance in risk classifications²

a Overall discordance=any difference in risk classification between the Recurrence Score results and other assays
b Study used non-standard Recurrence Score cut points for comparison of Recurrence Score vs. MMP

Multigene assays for breast cancer are not interchangeable

RCT = randomised clinical trial; ET = endocrine therapy; CT = chemotherapy

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}