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

Research output: Contribution to journalArticle

Abstract

Purpose: Transcriptional pathway activity and the molecular subtypes of breast cancer metastases have been shown to significantly influence patient postrelapse survival. Here, we further determine the relevance of clinically employed gene signatures in the advanced breast cancer (ABC) setting. Experimental Design: Sufficient RNA for expression profiling was obtained from distant metastatic or inoperable locoregional 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) postrelapse survival at all and locoregional 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 histologic grade (P < 0.05). When considering all sites of metastasis, only PAM50 was statistically significant in Kaplan–Meier analysis (Log-rank P = 0.008 and 0.008 for long- and short-term postrelapse breast cancer–specific survival, respectively). This significance remained in both uni- and multivariate 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 ABC patients.

Details

Authors
  • Nicholas P. Tobin
  • Arian Lundberg
  • Linda S. Lindström
  • J. Chuck Harrell
  • Theodoros Foukakis
  • Lena Carlsson
  • Zakaria Einbeigi
  • Barbro K. Linderholm
  • Niklas Loman
  • Martin Malmberg
  • Mårten Fernö
  • Kamila Czene
  • Charles M. Perou
  • Jonas Bergh
  • Thomas Hatschek
  • TEX Trialists Group
Organisations
External organisations
  • Karolinska University Hospital
  • Karolinska Institutet
  • Virginia Commonwealth University
  • Sahlgrenska University Hospital
  • Skåne University Hospital
  • University of North Carolina
  • University of Oxford
  • Sundsvall Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)7225-7231
Number of pages7
JournalClinical Cancer Research
Volume23
Issue number23
Publication statusPublished - 2017 Dec 1
Publication categoryResearch
Peer-reviewedYes