Expression of X-Linked Inhibitor of Apoptosis Protein (XIAP) in Breast Cancer Is Associated with Shorter Survival and Resistance to Chemotherapy.

Journal Article (Journal Article)

XIAP, the most potent inhibitor of cell death pathways, is linked to chemotherapy resistance and tumor aggressiveness. Currently, multiple XIAP-targeting agents are in clinical trials. However, the characterization of XIAP expression in relation to clinicopathological variables in large clinical series of breast cancer is lacking. We retrospectively analyzed non-metastatic, non-inflammatory, primary, invasive breast cancer samples for XIAP mRNA (n = 2341) and protein (n = 367) expression. XIAP expression was analyzed as a continuous value and correlated with clinicopathological variables. XIAP mRNA expression was heterogeneous across samples and significantly associated with younger patients' age (≤50 years), pathological ductal type, lower tumor grade, node-positive status, HR+/HER2- status, and PAM50 luminal B subtype. Higher XIAP expression was associated with shorter DFS in uni- and multivariate analyses in 909 informative patients. Very similar correlations were observed at the protein level. This prognostic impact was significant in the HR+/HER2- but not in the TN subtype. Finally, XIAP mRNA expression was associated with lower pCR rate to anthracycline-based neoadjuvant chemotherapy in both uni- and multivariate analyses in 1203 informative patients. Higher XIAP expression in invasive breast cancer is independently associated with poorer prognosis and resistance to chemotherapy, suggesting the potential therapeutic benefit of targeting XIAP.

Full Text

Duke Authors

Cited Authors

  • Devi, GR; Finetti, P; Morse, MA; Lee, S; de Nonneville, A; Van Laere, S; Troy, J; Geradts, J; McCall, S; Bertucci, F

Published Date

  • June 4, 2021

Published In

Volume / Issue

  • 13 / 11

PubMed ID

  • 34199946

Pubmed Central ID

  • PMC8200223

International Standard Serial Number (ISSN)

  • 2072-6694

Digital Object Identifier (DOI)

  • 10.3390/cancers13112807

Language

  • eng

Conference Location

  • Switzerland