Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
2015 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 1, 81-88 p.Article in journal (Refereed) Published
We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy A1 - Oxford Open Option F , 2015. Vol. 26, no 1, 81-88 p.
breast cancer metastases; metastasis characteristics; TEX randomized trial; gene expression; gene modules; biopsy at relapse
IdentifiersURN: urn:nbn:se:liu:diva-114243DOI: 10.1093/annonc/mdu498ISI: 000347416300013PubMedID: 25361981OAI: oai:DiVA.org:liu-114243DiVA: diva2:788702
Funding Agencies|Swedish Research Council [524-2011-6857, 521-2014-2057]; Swedish Research Council for Health, Working life and Welfare, FORTE [2014-1962]; Swedish Cancer Society; Cancer Society in Stockholm; King Gustaf V Jubilee Foundation; Swedish Breast Cancer Association (BRO); Swedish Research Council; Bristol-Myers Squibb Sweden AB; Pfizer Sweden AB; Roche Sweden AB; NCI Breast SPORE program [P50-CA58223-09A1]; Breast Cancer Research Foundation (CMP)2015-02-162015-02-162015-02-25