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Influence of Chemotherapy on EGFR Mutation Status Among Patients With Non–Small-Cell Lung Cancer
Open accessAbstract
PURPOSE: EGFR mutation is a predictor of epidermal growth factor receptor-tyrosine kinase inhibitor treatment response in patients with non-small-cell lung cancer (NSCLC). However, it remains unclear whether chemotherapy affects EGFR mutation status in NSCLC. We investigated the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC. PATIENTS AND METHODS: Samples were derived from three cohorts: one, 264 patients with advanced NSCLC who received first-line chemotherapy with matched pre- and postchemotherapy blood samples; two, 63 patients with stages IIb to IIIb disease with pre- and post-neoadjuvant chemotherapy tumor tissues; and three, 79 patients with advanced NSCLC who underwent palliative surgery. EGFR mutation status was determined and analyzed to reveal potential impact of chemotherapy. RESULTS: In the first cohort, EGFR mutations were detected in 34.5% of the prechemotherapy plasma samples (91 of 264) but in only 23.1% of the postchemotherapy plasma samples (61 of 264). The decrease in EGFR mutation rate was statistically significant (P < .001). Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response (PR) than patients with a reverse change (P = .037). A similar decrease in EGFR mutation rate was observed in tissues after neoadjuvant chemotherapy in the second cohort (34.9% [22 of 63] v 19.0% [12 of 63]; P = .013). In the third cohort, 38.0% of the tumors (30 of 79) showed an intratumor heterogeneity of EGFR mutation, whereas 62.0% (49 of 79) were homogeneous, either with EGFR mutation or no mutation. CONCLUSION: Our results suggest that chemotherapy may reduce EGFR mutation frequency in patients with NSCLC, likely the result of a preferential response of subclones with EGFR mutations in tumors with heterogeneous tumor cell populations.
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“Chemotherapy may selectively kill and inhibit mutant clones within the tumor, whereas wild type clones may proliferate, altering the relative proportion of EGFR-mutated/EGFR-wild type cells within the tumor mass.”
From A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives (2015) · cites this paper as [45]
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Metadata
- Authors
- Bai, H., Wang, Z., Chen, K., Zhao, J., Lee, J. J., Wang, S., Zhou, Q., Zhuo, M., Mao, L., An, T., Duan, J., Yang, L., Wu, M., Liang, Z., Wang, Y., Kang, X., & Wang, J.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Hua Bai, Zhijie Wang, Keneng Chen, Jun Zhao, Shuhang Wang, Minglei Zhuo, Tongtong An, Jianchun Duan, Lu Yang, Meina Wu, Zhen Liang, Yuyan Wang, Xiaozheng Kang, and Jie Wang, Peking University Cancer Hospital and Institute, Beijing; Qinghua Zhou, Tianjin Medical University General Hospital, Tianjin, China; J. Jack Lee, The University of Texas MD Anderson Cancer Center, Houston, TX; and Li Mao, University of Maryland School of Dentistry, Baltimore, MD.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2012-09-01
- Volume
- 30
- Issue
- 25
- Pages
- 3077-3083
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC5321076
- OpenAlex
- W2121641332
- Cited by
- 199
- References
- 40
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 11 · 2023: 1 · 2022: 11 · 2021: 6 · 2020: 3 · 2019: 8 · 2018: 20 · 2017: 22 · 2016: 21 · 2015: 23 · 2014: 33 · 2013: 33 · 2012: 1
- FWCI
- 23.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- EGFR mutation, non-small cell lung cancer, chemotherapy, plasma biomarkers, neoadjuvant chemotherapy, intratumoral heterogeneity, EGFR tyrosine kinase inhibitors, tumor subclones, treatment response
- MeSH terms
- Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, China, DNA, Neoplasm, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Neoplasm Staging, Palliative Care, Phenotype, Risk Factors, Time Factors, Cohort Studies, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Chi-Square Distribution, Treatment Outcome, Chemotherapy, Adjuvant, Risk Assessment, Genetic Predisposition to Disease, Neoadjuvant Therapy, Protein Kinase Inhibitors, ErbB Receptors
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