journal contribution
posted on 2023-03-31, 20:12 authored by 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 Supplementary Table 1. Primary tumour characteristics of patients included in the translational TEX trial Supplementary Table 2. Metastatic signature subtype split by primary tumour PR status and adjuvant therapy (N = 109) Supplementary Table 3. Long and short-term univariate Cox regression analysis for all signatures, post-relapse BCSS as clinical endpoint Supplementary Table 4. Long and short-term Likelihood ratios for all signatures in metastases from All, lymph nodes and other sites combined groups
Funding
BRECT
Swedish Cancer Society
Cancer Society in Stockholm
King Gustaf V Jubilee Foundation
Swedish Breast Cancer Association
Swedish Research Council
Bristol-Myers Squibb Sweden AB
Pfizer Sweden AB
Roche Sweden AB
NCI Breast SPORE
Breast Cancer Research Foundation
History
ARTICLE 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 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) 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. Clin Cancer Res; 23(23); 7225–31. ©2017 AACR.
