- Email: [email protected]
Expression of x-linked inhibitor of apoptosis protein (XIAP) and its association with clinicopathological parameters in invasive breast cancers
abstracts
Annals of Oncology
Expression of x-linked inhibitor of apoptosis protein (XIAP) and its association with clinicopathological parameters in invasive breast cancers
G. Devi1, P. Finetti2, J. Geradts3, S. McCall3, M. Morse4, S.J. Van Laere5, F. Bertucci6 1 Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC, USA, 2Medical Oncology and Molecular Oncology, Institut PaoliCalmettes,, Marseille, France, 3Pathology, Duke University Medical Center, Durham, NC, USA, 4Department of Medicine, Duke University Medical Center, Durham, NC, USA, 5 CORE, University of Antwerp, Antwerp, Belgium, 6Medical Oncology and Molecular Oncology, Institute Paoli Calmettes, Marseille, France Background: XIAP is the most potent inhibitor of both the extrinsic and intrinsic cell death pathways, which is linked to chemotherapy resistance and tumor aggressiveness. We analyzed the correlations between XIAP expression in invasive breast cancers and clinicopathological parameters including metastasis-free survival (MFS) and pathological complete response (pCR) to chemotherapy. Methods: Breast cancer databases comprising gene expression profiles with clinicopathological annotations from 8,636 non-redundant non-metastatic, non-inflammatory, primary, invasive patients were analyzed for XIAPexpression (binary variable, ”high” vs.“low” by using median as cut-off). XIAP immunohistochemistry was conducted in a cohort of post-chemotherapy mastectomy samples. Results: High XIAP mRNA expression was associated with pathological ductal type, pT1 tumor size, ER-positive, PR-positive, HRþ/HER2-, luminal A and B PAM50 subtypes. Analysis of MFS (3,454 non-stage 4) revealed shorter MFS (p ¼ 8.1E-03, log-
v92 | Breast Cancer, Early Stage
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.098/5576551 by guest on 26 October 2019
275P
Annals of Oncology
abstracts
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.098/5576551 by guest on 26 October 2019
rank test) associated with “XIAP-high” group. The hazard ratio for metastatic relapse was 1.20 (95%CI 1.05-1.38, p ¼ 8.17E-03, Wald test) in “XIAP-high” vs.“XIAP-low” group.In multivariate analysis, two variables (GGI and pT) remained significant, whereas the TN subtype and XIAPexpression tended to be (p ¼ 0.059). The prognostic value of XIAPwas significant in the multivariate analysis including two major signatures (70-gene signature, Recurrence Score), suggesting independent prognostic value. The same analysis, but in each molecular subtype separately, showed significant difference in the TN subtype (p ¼ 1.0E-03).Univariate analysis of pCR to anthracyclinebased neoadjuvant chemotherapy (1,203 patients) identified 20% pCR in the “XIAPhigh” group vs.26% in the “XIAP-low” group (p ¼ 0.015, logit function). Immunohistochemistry revealed high XIAP cytoplasmic staining only in invasive tumors and identified correlates with variables like grade, T, N, M and subtype status. Conclusions: XIAP-high” tumors are more prone to metastatic relapse and resistance to chemotherapy, suggesting the therapeutic benefit of targeting XIAP in the neoadjuvant setting. Legal entity responsible for the study: The authors. Funding: Department of Defense W81XWH-17-1-0297 (to G.R. Devi) and Duke School of Medicine Bridge Fund (to G.R.Devi). Disclosure: All authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz240 | v93
Annals of Oncology
Expression of x-linked inhibitor of apoptosis protein (XIAP) and its association with clinicopathological parameters in invasive breast cancers
G. Devi1, P. Finetti2, J. Geradts3, S. McCall3, M. Morse4, S.J. Van Laere5, F. Bertucci6 1 Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, NC, USA, 2Medical Oncology and Molecular Oncology, Institut PaoliCalmettes,, Marseille, France, 3Pathology, Duke University Medical Center, Durham, NC, USA, 4Department of Medicine, Duke University Medical Center, Durham, NC, USA, 5 CORE, University of Antwerp, Antwerp, Belgium, 6Medical Oncology and Molecular Oncology, Institute Paoli Calmettes, Marseille, France Background: XIAP is the most potent inhibitor of both the extrinsic and intrinsic cell death pathways, which is linked to chemotherapy resistance and tumor aggressiveness. We analyzed the correlations between XIAP expression in invasive breast cancers and clinicopathological parameters including metastasis-free survival (MFS) and pathological complete response (pCR) to chemotherapy. Methods: Breast cancer databases comprising gene expression profiles with clinicopathological annotations from 8,636 non-redundant non-metastatic, non-inflammatory, primary, invasive patients were analyzed for XIAPexpression (binary variable, ”high” vs.“low” by using median as cut-off). XIAP immunohistochemistry was conducted in a cohort of post-chemotherapy mastectomy samples. Results: High XIAP mRNA expression was associated with pathological ductal type, pT1 tumor size, ER-positive, PR-positive, HRþ/HER2-, luminal A and B PAM50 subtypes. Analysis of MFS (3,454 non-stage 4) revealed shorter MFS (p ¼ 8.1E-03, log-
v92 | Breast Cancer, Early Stage
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.098/5576551 by guest on 26 October 2019
275P
Annals of Oncology
abstracts
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz240.098/5576551 by guest on 26 October 2019
rank test) associated with “XIAP-high” group. The hazard ratio for metastatic relapse was 1.20 (95%CI 1.05-1.38, p ¼ 8.17E-03, Wald test) in “XIAP-high” vs.“XIAP-low” group.In multivariate analysis, two variables (GGI and pT) remained significant, whereas the TN subtype and XIAPexpression tended to be (p ¼ 0.059). The prognostic value of XIAPwas significant in the multivariate analysis including two major signatures (70-gene signature, Recurrence Score), suggesting independent prognostic value. The same analysis, but in each molecular subtype separately, showed significant difference in the TN subtype (p ¼ 1.0E-03).Univariate analysis of pCR to anthracyclinebased neoadjuvant chemotherapy (1,203 patients) identified 20% pCR in the “XIAPhigh” group vs.26% in the “XIAP-low” group (p ¼ 0.015, logit function). Immunohistochemistry revealed high XIAP cytoplasmic staining only in invasive tumors and identified correlates with variables like grade, T, N, M and subtype status. Conclusions: XIAP-high” tumors are more prone to metastatic relapse and resistance to chemotherapy, suggesting the therapeutic benefit of targeting XIAP in the neoadjuvant setting. Legal entity responsible for the study: The authors. Funding: Department of Defense W81XWH-17-1-0297 (to G.R. Devi) and Duke School of Medicine Bridge Fund (to G.R.Devi). Disclosure: All authors have declared no conflicts of interest.
doi:10.1093/annonc/mdz240 | v93