Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer
| Autor: | Chatzipli, Aikaterini, Bonnefoi, Hervé, Macgrogan, Gaetan, Sentis, Julie, Cameron, David, Poncet, Coralie, Abadie-lacourtoisie, Sophie, Bodmer, Alexandre, Brain, Etienne, Cufer, Tanja, Campone, Mario, Luporsi, Elisabeth, Moldovan, Cristian, Petit, Thierry, Piccart, Martine, Priou, Franck, Senkus, Elsbieta, Zaman, Khalil, Iggo, Richard |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | 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 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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