50-Gene Score Boosts Postmenopausal Breast Cancer Prognostic Accuracy

The PAM50 risk of recurrence score significantly increases the ability to predict distant recurrence-free survival for women with postmenopausal hormone receptor-positive breast cancer

medwireNews: The PAM50 risk of recurrence (ROR) score significantly improves prognostic accuracy for postmenopausal women with Oestrogen receptor (ER)-positive early-stage breast cancer taking tamoxifen alone or with anastrozole, research suggests.

Adding the intrinsic subtype classification given by the 50-Gene score significantly increased the already highly significant ability of the clinical linear predictor (CLP) score, derived from tumour size, grade and node status, to predict distant recurrence-free survival (DRFS).

The impact of the PAM50 hazard ratio (HR) of 1.03 equates to a 37.5% increase in the risk of relapse for each 10-point increase in the ROR score, explain Michael Gnant, from the Medical University of Vienna in Austria, and co-workers.

Using the PAM50 ROR to classify patients into high-, intermediate- and low-risk groups also significantly increased prognostic ability compared with CLP alone, giving 10-year DRFS probability of 79.9%, 91.3% and 96.7%, respectively. And patients classified with the luminal A intrinsic subtype using the PAM50 ROR had a significantly greater odds of DRFS than luminal B patients, at a hazard ratio of 2.85, with prognostic ability again significantly increased over that of CLP alone.

The study, performed in 1478 postmenopausal patients participating in the ABCSG-8 trial, is the largest yet to use the PAM50 test and has shown similar results to those of the ATAC cohort, therefore fulfilling the criteria for level 1 evidence for prospective–retrospective study designs, Michael Gnant and team say in Annals of Oncology.

“If a multigene expression test—as we demonstrate for PAM50-defined ROR—is consistently able to define a low-risk group with a 10-year metastasis risk of <3.5% in multiple trial populations, it is fair to say that it is highly unlikely that additional chemotherapy would be able to improve this outcome even numerically—not to mention the unfavorable harm/benefit ratio with respect to treatment side-effects,” the researchers write.

They therefore conclude: “This added prognostic information should aid physicians in stratifying patients into distinct risk categories with different prognoses among node-negative and even node-positive patient populations, thereby aiding physicians in determining whether additional chemotherapy beyond endocrine therapy is required.”


Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 2013; First published online: December 16, 2013. doi: 10.1093/annonc/mdt494.

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