Abstract P2-11-06: Comparison of PAM50 risk of recurrence (ROR) scores with EndoPredict for predicting risk of distant metastasis in ER+/HER2-, early node-positive breast cancer patients treated with adjuvant chemotherapy - A GEICAM/ 9906 sub-study
Authors: Martin M , Brase JC , Perou CM , Ruiz A , Prat A , Weber KE , Calvo L , Petry C , Bernard PS , Ruiz-Borrego M , Kronenwett R , Santaballa AM , Rodriguez CA , Alvarez IM , Segui MA , Casas M , Carrasco E , Caballero R , Rodriguez-Lescure A 
Published: August 2014

Background:

Several prognostic multigene tests are available for the management of breast cancer patients, but so far there is little data available directly comparing the classification performance of different breast cancer tests in the same patient cohort. Here, we compared the prognostic performance of two second generation multigene tests in ER+/HER2- early node-positive breast cancer patients treated with adjuvant chemotherapy followed by endocrine therapy.

Patients and methods:

The EndoPredict (EP) score and two research laboratory-based versions of the PAM50 risk of recurrence (ROR based on subtype [ROR-S] and based on subtype and proliferation [ROR-P]) score were compared in 536 ER+/HER2- breast cancer patients who participated in the GEICAM/ 9906 trial. Patients had either been treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P), and endocrine therapy. ROR and EP scores were combined with clinical information to obtain the following hybrid scores as published before: a) ROR-T score (subtype and tumor size), b) ROR-PT score (subtype, proliferation and tumor size) scores, and c) EPclin score (EP Score plus tumor size and nodal status). Each patient was assigned to risk categories according to pre-specified cut-off levels for the scores. The primary endpoint was distant metastasis. Metastasis rates were estimated using the Kaplan-Meier method. C-index analysis was used to estimate the performance of the different scores.

Results:

The PAM50 ROR-S and ROR-P scores, and the EP score were prognostic in patients with ER+/HER2- tumors and consistently identified a low-risk group with a particular good outcome (10 year MFS rate - ROR-S: 81.7%, ROR-P: 82.9% and EP: 89.4%). Combining the molecular signatures with clinical information, improved the prognostic performance of all signatures (10 year MFS rate - ROR-T: 83.4%, ROR-PT: 87.3% and EPclin: 100%). All signatures added prognostic information to common clinical parameters. Among the signatures evaluated only EPclin added a significantly improved prediction of distant metastasis to ROR-T (p &lt; 0.001) and ROR-PT (p &lt; 0.001), which may be due to the feature that EPClin includes a term for node status, but which is not included in any ROR-based model.

Conclusions:

Our study suggests that PAM50 ROR and EP can be used to reliably predict risk of distant metastasis in node-positive ER+/HER2- breast cancer patients treated with chemotherapy. There was no significant difference between the molecular signatures in terms of low risk classification.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-06.