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Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer
BACKGROUND: Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved surviv...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000975/ https://www.ncbi.nlm.nih.gov/pubmed/29898752 http://dx.doi.org/10.1186/s13058-018-0989-8 |
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author | Norton, Nadine Fox, Nicholas McCarl, Christie-Ann Tenner, Kathleen S. Ballman, Karla Erskine, Courtney L. Necela, Brian M. Northfelt, Donald Tan, Winston W. Calfa, Carmen Pegram, Mark Colon-Otero, Gerardo Perez, Edith A. Clynes, Raphael Knutson, Keith L. |
author_facet | Norton, Nadine Fox, Nicholas McCarl, Christie-Ann Tenner, Kathleen S. Ballman, Karla Erskine, Courtney L. Necela, Brian M. Northfelt, Donald Tan, Winston W. Calfa, Carmen Pegram, Mark Colon-Otero, Gerardo Perez, Edith A. Clynes, Raphael Knutson, Keith L. |
author_sort | Norton, Nadine |
collection | PubMed |
description | BACKGROUND: Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. METHODS: Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. RESULTS: Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). CONCLUSIONS: These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00005970. Registered on July 5, 2000. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-0989-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6000975 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60009752018-06-26 Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer Norton, Nadine Fox, Nicholas McCarl, Christie-Ann Tenner, Kathleen S. Ballman, Karla Erskine, Courtney L. Necela, Brian M. Northfelt, Donald Tan, Winston W. Calfa, Carmen Pegram, Mark Colon-Otero, Gerardo Perez, Edith A. Clynes, Raphael Knutson, Keith L. Breast Cancer Res Research Article BACKGROUND: Resected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively. METHODS: Pre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival. RESULTS: Prior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04). CONCLUSIONS: These results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00005970. Registered on July 5, 2000. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-018-0989-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-14 2018 /pmc/articles/PMC6000975/ /pubmed/29898752 http://dx.doi.org/10.1186/s13058-018-0989-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Norton, Nadine Fox, Nicholas McCarl, Christie-Ann Tenner, Kathleen S. Ballman, Karla Erskine, Courtney L. Necela, Brian M. Northfelt, Donald Tan, Winston W. Calfa, Carmen Pegram, Mark Colon-Otero, Gerardo Perez, Edith A. Clynes, Raphael Knutson, Keith L. Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title | Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title_full | Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title_fullStr | Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title_full_unstemmed | Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title_short | Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer |
title_sort | generation of her2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected her2 breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000975/ https://www.ncbi.nlm.nih.gov/pubmed/29898752 http://dx.doi.org/10.1186/s13058-018-0989-8 |
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