Baseline Mutations and Up-Regulation of PI3K-AKT Pathway Serve as Potential Indicators of Lack of Response to Neoadjuvant Chemotherapy in Stage II/III Breast Cancer.

PI3K-AKT pathway PIK3CA mutations neoadjuvant chemotherapy (NAC) pathologic complete response (pCR) stage II/III breast cancer (BC)

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2021
Historique:
received: 28 09 2021
accepted: 28 12 2021
entrez: 28 4 2022
pubmed: 29 4 2022
medline: 29 4 2022
Statut: epublish

Résumé

Neoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients' genomic characteristics. We prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery. Patients received epirubicin and cyclophosphamide for 4 cycles, followed by another 4-cycle docetaxel, and human epidermal growth factor receptor (HER2) positive patients were additionally treated with herceptin when using docetaxel (EC-T(H)). NAC responses were evaluated as pathologic complete response (pCR) or non-pathologic complete response (non-pCR). Genomic features related to NAC responses were identified by profiling baseline tumor tissues sampled one day before NAC, using whole-exome sequencing. Differentially expressed genes and up-/down-regulated pathways were investigated by performing RNA-sequencing. A total of 25 stage II/III BC patients were enrolled, including 5 patients ultimately evaluated as pCR and 20 patients evaluated as non-pCR. Compared to BC patients achieving pCR to NAC, aberrant activation of PI3K-AKT pathway genes were more frequently observed in patients not achieving pCR, consistent with the significant up-regulation of PI3K-AKT pathway gene expression in the non-pCR subgroup. Together, these findings indicate that upregulated PI3K-AKT pathway serves as a potential indicator of lack of response to NAC in stage II/III BC patients, and other effective therapeutic options are urgently needed for those resistant patients.

Sections du résumé

Background UNASSIGNED
Neoadjuvant chemotherapy (NAC) has been expanded to hormone receptor (HR) positive breast cancer (BC) patients with operable disease, to increase the likelihood of breast-conserving surgery. Genomic profiling at baseline would reveal NAC response relevant genomic features and signaling pathways, guiding clinical NAC utilization based on patients' genomic characteristics.
Methods UNASSIGNED
We prospectively studied stage II/III BC patients who were eligible for breast-conserving surgery. Patients received epirubicin and cyclophosphamide for 4 cycles, followed by another 4-cycle docetaxel, and human epidermal growth factor receptor (HER2) positive patients were additionally treated with herceptin when using docetaxel (EC-T(H)). NAC responses were evaluated as pathologic complete response (pCR) or non-pathologic complete response (non-pCR). Genomic features related to NAC responses were identified by profiling baseline tumor tissues sampled one day before NAC, using whole-exome sequencing. Differentially expressed genes and up-/down-regulated pathways were investigated by performing RNA-sequencing.
Results UNASSIGNED
A total of 25 stage II/III BC patients were enrolled, including 5 patients ultimately evaluated as pCR and 20 patients evaluated as non-pCR.
Conclusion UNASSIGNED
Compared to BC patients achieving pCR to NAC, aberrant activation of PI3K-AKT pathway genes were more frequently observed in patients not achieving pCR, consistent with the significant up-regulation of PI3K-AKT pathway gene expression in the non-pCR subgroup. Together, these findings indicate that upregulated PI3K-AKT pathway serves as a potential indicator of lack of response to NAC in stage II/III BC patients, and other effective therapeutic options are urgently needed for those resistant patients.

Identifiants

DOI: 10.3389/fonc.2021.784985 PMID: 35480699 PMC: PMC9036956
pubmed: 35480699
doi: 10.3389/fonc.2021.784985
pmc: PMC9036956
doi:

Types de publication

Journal Article

Langues

eng

Pagination

784985

Informations de copyright

Copyright © 2022 Dong, Shan, Han, Zhao, Wang, Zhu, Ou, Ma and Pan.

Déclaration de conflit d'intérêts

XZ, FW, LZ, and QO are employees of Nanjing Geneseeq Technology Inc., China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Menghao Dong (M)

Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Benjie Shan (B)

Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Xinghua Han (X)

Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Xiaotian Zhao (X)

Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.

Fufeng Wang (F)

Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.

Liuqing Zhu (L)

Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.

Qiuxiang Ou (Q)

Geneseeq Research Institute, Nanjing Geneseeq Technology Inc., Nanjing, China.

Xiaopeng Ma (X)

Department of Thyroid and Breast Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Yueyin Pan (Y)

Department of Medical Oncology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Classifications MeSH