Correlation Between Oncotype DX, PREDICT and the Nottingham Prognostic Index: Implications for the Management of Early Breast Cancer.

Introduction Breast cancer remains the most common cancer diagnosis in the UK. The current clinical practice utilises two different types of modalities to estimate the prognosis, risk of recurrence and benefit from adjuvant chemotherapy treatment in patients with early breast cancer. The first set of modalities includes risk calculators based on clinicopathological features, e.g. PREDICT or the Nottingham Prognostic Index (NPI); the second includes genetic profiling of tumour tissue using Oncotype DX (ODX; Genomic Health, Redwood City, CA) testing. PREDICT, NPI and ODX stratify breast cancers into high-, intermediate- and low-risk categories to help guide adjuvant chemotherapy treatment decisions. This study compares PREDICT, NPI and ODX Recurrence Scores (RS), with the aim of assessing 1) the correlation between the RS for PREDICT, NPI and ODX and 2) whether early breast cancer patients are stratified into similar risk categories by all three modalities. Methods This retrospective study included early breast cancer patients treated at a National Health Service (NHS) hospital over a 12-month period (October 1, 2017 to September 30, 2018). Inclusion criteria: consecutive patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. All patients were discussed at the local multidisciplinary team (MDT) meeting and underwent ODX testing. Exclusion criteria: patients without ODX test scores; patients with an in-breast recurrence; patients who did not undergo a sentinel lymph node biopsy (SLNB); and patients with ductal carcinoma in situ (DCIS) only. NPI and PREDICT scores were calculated for each patient using online tools, and ODX data was obtained through Genomic Health and MDT records. Patients were risk-stratified into high, intermediate and low risk of recurrence groups based on their PREDICT, NPI and ODX scores. The thresholds for risk stratification were based on current practice, which is evidence-based. Correlations between PREDICT, NPI and ODX scores were analysed using Spearman's correlation coefficient. Results Forty-six patients (mean age: 56 years), with a total of 57 early breast cancers, underwent ODX testing. Risk categories generated by PREDICT very strongly correlated with NPI for all patients (r=0.92; P<0.0001). However, the RS generated by ODX testing only strongly correlated for patients with low-risk PREDICT scores (r=0.51; P=0.0134), while no correlation between RS and PREDICT was observed for patients with intermediate- or high-risk PREDICT scores (r=-0.0064; P=0.9767). Similar results were seen between NPI and RS. Overall, only 19/46 (41.3%) patients had an RS which corresponded to PREDICT risk category, while 18/46 (39.1%) patients had an RS that indicated a higher risk of recurrence than PREDICT, and 9/46 (19.6%) patients had an RS indicating a lower risk of recurrence than PREDICT. Similar results were found when comparing RS and NPI. Conclusion The risk of recurrence estimated by ODX in patients deemed low risk by PREDICT or NPI highly correlated, while no such correlation existed in patients with an estimated intermediate- or high-risk breast cancer. In PREDICT- or NPI-estimated intermediate- and high-risk patients, ODX provided valuable additional prognostic information to guide adjuvant treatment, while the potential avoidance of ODX testing in low-risk patients presents significant cost-savings.