Chemotherapy Modulates Endocrine Therapy-Related Resistance Mutations in Metastatic Breast Cancer
| Autor: | Liping Liu, Zheyu Hu, Dabo Zhou, Mengjia Xiao, Yu Tang, Qiongzhi He, Quchang Ouyang, Jingyu Liu, Yikai Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Original article Cancer Research medicine.medical_specialty medicine.medical_treatment Gene mutation medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Breast cancer Internal medicine Medicine Mutation frequency Chemotherapy Mutation Erratum/Corrigendum Everolimus business.industry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Metastatic breast cancer 030104 developmental biology 030220 oncology & carcinogenesis business Progressive disease medicine.drug |
| Zdroj: | Translational Oncology, Vol 12, Iss 5, Pp 764-774 (2019) Translational Oncology |
| ISSN: | 1936-5233 |
| Popis: | PURPOSE: Accumulation of PIK3CA, ESR1, and GATA3 mutations results in resistance to endocrine therapy in breast cancer patients; however, the response of these genes to chemotherapy is unclear. Therefore, we sought to evaluate the genetic response of circulating tumor DNA (ctDNA) to chemotherapy in metastatic breast cancer patients. METHODS: The mutation frequency of 1021 genes was examined prior to chemotherapy in ctDNA of 44 estrogen receptor–positive metastatic breast cancer patients. These genes were evaluated again in a subset of patients (n=24) following chemotherapy. Mutation frequency was defined as the percentage of mutations found in ctDNA compared to total cell-free DNA. RESULTS: Prior to chemotherapy, PIK3CA was the most commonly mutated gene, with mutation found in 22 of the metastatic breast cancer patients. Following chemotherapy, 16 patients exhibited progressive disease (PD), and 8 patients experienced no progression (non-PD). PIK3CA mutation frequency increased in 56.25% (9/16) of the PD patients but decreased in 62.5% (5/8) of the non-PD patients. As a result, more PD patients exhibited increased PIK3CA mutation frequency than non-PD patients (56.25% vs 0%, P=.002). Further, ESR1 and GATA3 mutations correlated with PIK3CA mutation. Interestingly, patients receiving the mTOR inhibitor everolimus exhibited a lower progression rate (0% vs 62.5%, P=.001), and the combination of everolimus and chemotherapy effectively suppressed PIK3CA, ESR1, and GATA3 gene mutations. CONCLUSION: Together, these results suggest that mTOR inhibition may be a useful chemotherapy adjuvant to suppress chemotherapy-induced gene mutations that render tumors resistant to endocrine therapy in metastatic breast cancer patients with PD. |
| Databáze: | OpenAIRE |
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