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PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer
BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814131/ https://www.ncbi.nlm.nih.gov/pubmed/36323880 http://dx.doi.org/10.1038/s41416-022-02021-z |
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author | Shi, Qiyun Xuhong, Juncheng Luo, Tao Ge, Jia Liu, Feng Lan, Yang Chen, Qingqiu Tang, Peng Fan, Linjun Chen, Li Liang, Yan Wang, Minghao Hu, Ying Zhang, Yi Bian, Xiuwu Qi, Xiaowei Jiang, Jun |
author_facet | Shi, Qiyun Xuhong, Juncheng Luo, Tao Ge, Jia Liu, Feng Lan, Yang Chen, Qingqiu Tang, Peng Fan, Linjun Chen, Li Liang, Yan Wang, Minghao Hu, Ying Zhang, Yi Bian, Xiuwu Qi, Xiaowei Jiang, Jun |
author_sort | Shi, Qiyun |
collection | PubMed |
description | BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (P(adjusted) = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827−0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy. |
format | Online Article Text |
id | pubmed-9814131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98141312023-01-06 PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer Shi, Qiyun Xuhong, Juncheng Luo, Tao Ge, Jia Liu, Feng Lan, Yang Chen, Qingqiu Tang, Peng Fan, Linjun Chen, Li Liang, Yan Wang, Minghao Hu, Ying Zhang, Yi Bian, Xiuwu Qi, Xiaowei Jiang, Jun Br J Cancer Article BACKGROUND: Neoadjuvant treatment with a dual anti-human epidermal growth factor receptor 2 (HER2) blockade with pyrotinib and trastuzumab has been shown to be effective for HER2-positive breast cancer. METHODS: The genomic characteristics of 425 cancer-related genes from the archived tumour blocks of 50 patients enrolled in a prospective neoadjuvant pyrotinib and trastuzumab plus chemotherapy clinical trial (ChiCTR1900022293) were assessed by next-generation sequencing (NGS). The relationship between tumour biomarkers and the postoperative pathological complete response (pCR) were explored. RESULTS: Forty-five patients completed neoadjuvant chemotherapy and final surgery, of which 26 (58%) achieved a pCR. Among all driver gene mutations, PIK3CA mutation was screened out for having a significant relationship with the treatment response. The pCR rate of patients with wild-type PIK3CA was significantly higher than patients with mutated PIK3CA (80.8% vs. 26.3%; P = 0.00057), and remained significant after a multiple comparison adjustment (P(adjusted) = 0.024). We further evaluated the predictive value with logistic regression model of clinical features, genetic biomarkers or both, an AUC of 0.912 (95% CI: 0.827−0.997) was achieved in the integrated model. CONCLUSIONS: Our data suggest that HER2-positive breast cancers with activating mutations in PIK3CA are less likely to benefit from pyrotinib combined with trastuzumab neoadjuvant therapy. Nature Publishing Group UK 2022-11-02 2023-01-26 /pmc/articles/PMC9814131/ /pubmed/36323880 http://dx.doi.org/10.1038/s41416-022-02021-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Shi, Qiyun Xuhong, Juncheng Luo, Tao Ge, Jia Liu, Feng Lan, Yang Chen, Qingqiu Tang, Peng Fan, Linjun Chen, Li Liang, Yan Wang, Minghao Hu, Ying Zhang, Yi Bian, Xiuwu Qi, Xiaowei Jiang, Jun PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title | PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title_full | PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title_fullStr | PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title_full_unstemmed | PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title_short | PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer |
title_sort | pik3ca mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for her2-positive breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814131/ https://www.ncbi.nlm.nih.gov/pubmed/36323880 http://dx.doi.org/10.1038/s41416-022-02021-z |
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