Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer

We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were...

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Main Authors: Yong-Seok Kim, Der Sheng Sun, Juneyoung Ahn, Yongseon Kim, Jung-Sook Yoon, Hye Sung Won
Format: Article
Language:English
Published: MDPI AG 2022-07-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/15/3650
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author Yong-Seok Kim
Der Sheng Sun
Juneyoung Ahn
Yongseon Kim
Jung-Sook Yoon
Hye Sung Won
author_facet Yong-Seok Kim
Der Sheng Sun
Juneyoung Ahn
Yongseon Kim
Jung-Sook Yoon
Hye Sung Won
author_sort Yong-Seok Kim
collection DOAJ
description We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies’ nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including <i>WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP</i>, and <i>EREG</i>, and two genes were downregulated, including <i>CXCL9</i> and <i>GNLY</i>. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.
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spelling doaj.art-19449d233b0a470da2fcae6513835c6f2023-12-03T12:30:42ZengMDPI AGCancers2072-66942022-07-011415365010.3390/cancers14153650Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast CancerYong-Seok Kim0Der Sheng Sun1Juneyoung Ahn2Yongseon Kim3Jung-Sook Yoon4Hye Sung Won5Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaClinical Research Laboratory, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaDepartment of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, KoreaWe aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies’ nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including <i>WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP</i>, and <i>EREG</i>, and two genes were downregulated, including <i>CXCL9</i> and <i>GNLY</i>. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.https://www.mdpi.com/2072-6694/14/15/3650breast cancerhuman epidermal growth factor receptor 2recurrencetumor inflammation signature
spellingShingle Yong-Seok Kim
Der Sheng Sun
Juneyoung Ahn
Yongseon Kim
Jung-Sook Yoon
Hye Sung Won
Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
Cancers
breast cancer
human epidermal growth factor receptor 2
recurrence
tumor inflammation signature
title Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
title_full Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
title_fullStr Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
title_full_unstemmed Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
title_short Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer
title_sort analysis of genomic alterations associated with recurrence in early stage her2 positive breast cancer
topic breast cancer
human epidermal growth factor receptor 2
recurrence
tumor inflammation signature
url https://www.mdpi.com/2072-6694/14/15/3650
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