PAM50 provides prognostic information when applied to the lymph node metastases of advanced breast cancer patients

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient post-relapse survival. Here we further determine the relevance of clinically employed gene signatures in the advanced breast cancer setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable loco-regional relapse tissue by fine needle aspiration from 109 patients of the Swedish TEX clinical trial. Gene signatures (GGI, 70 gene, Recurrence score, Cell Cycle Score, Risk of Recurrence score and PAM50) were applied to all metastases and their relationship to long- (5 year) and short-term (1.5 year) post-relapse survival at all and loco-regional lymph nodes (n= 40) versus other metastatic sites (n=69) combined was assessed using Kaplan-Meier and/or multivariate Cox regression analyses. Results: The majority of metastases were classified into intermediate or high-risk groups by all signatures and a significant association was found between metastatic signature subgroups and primary tumor estrogen receptor status and histological grade (P < 0.05). When considering all sites of metastasis only PAM50 was statistically significant in Kaplan-Meier analysis (Logrank P = 0.008 and 0.008 for long and short term post-relapse BCSS, respectively). This significance remained in both uni and multi-variate models when restricting analyses to lymph node metastases only and a similar trend was observed in other metastatic sites combined, but did not reach formal significance. Conclusions: Our findings are the first to demonstrate that the PAM50 signature can provide prognostic information from the lymph node metastases of advanced breast cancer patients.

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