Combined pathologic-genomic algorithm for early stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.

Abstract

Background

The 21-gene recurrence score (RS) [Oncotype DX®] partitions hormone receptor positive, node negative breast cancers into 3 risk groups for recurrence. The AAMC Model has previously been shown to accurately predict RS risk categories using standard pathology data. A Pathologic-Genomic (P-G) Algorithm then is presented using the AAMC model, and reserving the RS assay only for AAMC intermediate risk patients.

Patients and Methods

A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC Model. Using Kaplan-Meier methods, five-year distant recurrence rates (DRR) were evaluated within each risk group, and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G Algorithm and compared to DRR for RS risk groups and the AAMC Model's risk groups.

Results

A total of 1,268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G Algorithm, more patients were categorized as either low- or high-risk, and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G Algorithm, 44% (552/1268) of patients would have avoided RS testing.

Conclusions

AAMC Model is capable of predicting five-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G Algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus the P-G Algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.