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Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer
- Source :
- Chatzipli, A, Bonnefoi, H, Macgrogan, G, Sentis, J, Cameron, D, Poncet, C, Abadie-lacourtoisie, S, Bodmer, A, Brain, E, Cufer, T, Campone, M, Luporsi, E, Moldovan, C, Petit, T, Piccart, M, Priou, F, Senkus, E, Zaman, K & Iggo, R 2021, ' Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer ', British Journal of Cancer . https://doi.org/10.1038/s41416-021-01526-3, Br J Cancer
- Publication Year :
- 2021
-
Abstract
- Background Treatment of patients with residual disease after neoadjuvant chemotherapy for breast cancer is an unmet clinical need. We hypothesised that tumour subclones showing expansion in residual disease after chemotherapy would contain mutations conferring drug resistance. Methods We studied oestrogen receptor and/or progesterone receptor-positive, HER2-negative tumours from 42 patients in the EORTC 10994/BIG 00-01 trial who failed to achieve a pathological complete response. Genes commonly mutated in breast cancer were sequenced in pre and post-treatment samples. Results Oncogenic driver mutations were commonest in PIK3CA (38% of tumours), GATA3 (29%), CDH1 (17%), TP53 (17%) and CBFB (12%); and amplification was commonest for CCND1 (26% of tumours) and FGFR1 (26%). The variant allele fraction frequently changed after treatment, indicating that subclones had expanded and contracted, but there were changes in both directions for all of the commonly mutated genes. Conclusions We found no evidence that expansion of clones containing recurrent oncogenic driver mutations is responsible for resistance to neoadjuvant chemotherapy. The persistence of classic oncogenic mutations in pathways for which targeted therapies are now available highlights their importance as drug targets in patients who have failed chemotherapy but provides no support for a direct role of driver oncogenes in resistance to chemotherapy. CLINICALTRIALS.GOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
Neoplasm, Residual
Receptor, ErbB-2
medicine.medical_treatment
Estrogen receptor
Antineoplastic Agents
Breast Neoplasms
Drug resistance
Disease
Article
CDH1
Cyclin D1
Breast cancer
Gene Frequency
Internal medicine
Humans
Medicine
Gene Regulatory Networks
Chemotherapy
biology
business.industry
Gene Amplification
GATA3
Sequence Analysis, DNA
medicine.disease
Neoadjuvant Therapy
Treatment Outcome
Receptors, Estrogen
Mutation
biology.protein
Female
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Chatzipli, A, Bonnefoi, H, Macgrogan, G, Sentis, J, Cameron, D, Poncet, C, Abadie-lacourtoisie, S, Bodmer, A, Brain, E, Cufer, T, Campone, M, Luporsi, E, Moldovan, C, Petit, T, Piccart, M, Priou, F, Senkus, E, Zaman, K & Iggo, R 2021, ' Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer ', British Journal of Cancer . https://doi.org/10.1038/s41416-021-01526-3, Br J Cancer
- Accession number :
- edsair.doi.dedup.....425e98335b33e02808f2312da91a42df