Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
| Autor: | Tejal Patel, Toniva Boone, Jenny C. Chang, Angel Rodriguez, Polly A. Niravath, Kartik Anand, Jorge Darcourt, Joe Ensor, Anna Belcheva |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Oncology medicine.medical_specialty DNA Repair Anthracycline Science medicine.medical_treatment Antineoplastic Agents Triple Negative Breast Neoplasms Article 03 medical and health sciences Breast cancer 0302 clinical medicine Germline mutation Internal medicine Exome Sequencing medicine Clinical endpoint Humans Everolimus 030212 general & internal medicine Triple-negative breast cancer Aged Cisplatin Chemotherapy Multidisciplinary business.industry TOR Serine-Threonine Kinases High-Throughput Nucleotide Sequencing Middle Aged medicine.disease Survival Analysis Neoadjuvant Therapy Cancer therapeutic resistance Treatment Outcome 030220 oncology & carcinogenesis Medicine Drug Therapy Combination Female business medicine.drug |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-80081-y |
| Popis: | Triple-negative breast cancer (TNBC) patients who do not achieve pathologic complete response post neoadjuvant chemotherapy have a poor prognosis. Alteration in PI3K/mTOR plus DNA repair pathways are some of the major mechanisms of chemotherapy resistance. We designed an open-label phase II clinical trial to evaluate if the combination of everolimus (mTOR inhibitor) plus cisplatin (interferes with DNA function) will improve the rate of pathologic response, as assessed by residual cancer burden (RCB). Twenty-four Stage II/III TNBC patients with residual cancer > 1 cm post neoadjuvant anthracycline and taxane-based chemotherapy were enrolled. Patients received everolimus daily orally at 10 mg for 12 weeks and cisplatin IV at 20 mg/m2 weekly for 4 cycles (21-day cycle), until definitive surgery. The primary endpoint was the rate of RCB-0-I at the surgery. The median age of the whole cohort was 50.1 years, with 66.7% non-Hispanic Caucasians. Of the 24 patients enrolled, 22 were included in the efficacy analysis. Twenty-one patients underwent definitive surgery while one patient developed distant metastasis. Five patients had RCB-I at surgery, a response rate of 23% (5/22). Patients with germline PALB2 mutation or somatic PI3KCA mutation had a pathologic response, achieving RCB-I at the surgery. Three patients had metaplastic histology achieving RCB-I at the surgery. Estimated OS at 1 year was 100% in the RCB-I group vs. 76.5% in others, which was not statistically significant due to the small sample size. Certain cohorts including PALB2 germline mutation carrier and somatic PI3KCA mutations warrant further investigation.Trial registration: Clinicaltrials.gov identifier: NCT01931163. https://clinicaltrials.gov/ct2/show/NCT01931163. |
| Databáze: | OpenAIRE |
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