Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy

Abstract 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...

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Autores principales:	Kartik Anand, Tejal Patel, Polly Niravath, Angel Rodriguez, Jorge Darcourt, Anna Belcheva, Toniva Boone, Joe Ensor, Jenny Chang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d34983028cb9441c92231a1bc62f5312
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spelling	oai:doaj.org-article:d34983028cb9441c92231a1bc62f53122021-12-02T15:08:26ZTargeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy10.1038/s41598-020-80081-y2045-2322https://doaj.org/article/d34983028cb9441c92231a1bc62f53122021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80081-yhttps://doaj.org/toc/2045-2322Abstract 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 .Kartik AnandTejal PatelPolly NiravathAngel RodriguezJorge DarcourtAnna BelchevaToniva BooneJoe EnsorJenny ChangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kartik Anand Tejal Patel Polly Niravath Angel Rodriguez Jorge Darcourt Anna Belcheva Toniva Boone Joe Ensor Jenny Chang Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
description	Abstract 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 .
format	article
author	Kartik Anand Tejal Patel Polly Niravath Angel Rodriguez Jorge Darcourt Anna Belcheva Toniva Boone Joe Ensor Jenny Chang
author_facet	Kartik Anand Tejal Patel Polly Niravath Angel Rodriguez Jorge Darcourt Anna Belcheva Toniva Boone Joe Ensor Jenny Chang
author_sort	Kartik Anand
title	Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
title_short	Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
title_full	Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
title_fullStr	Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
title_full_unstemmed	Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
title_sort	targeting mtor and dna repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d34983028cb9441c92231a1bc62f5312
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Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy

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