Please use this identifier to cite or link to this item: https://repository.southwesthealthcare.com.au/swhealthcarejspui/handle/1/3476
Journal Title: Tailored NEOadjuvant epirubicin, cyclophosphamide and Nanoparticle Albumin-Bound paclitaxel for breast cancer: The phase II NEONAB trial-Clinical outcomes and molecular determinants of response
Authors: Murphy, Caitlin
Muscat, Andrea
Ashley, David
Mukaro, Violet
West, Linda
Liao, Yang
Chisanga, David
Shi, Wei
Collins, Ian M.
Baron-Hay, Sally
Patil, Sujata
Lindeman, Geoffrey
Khasraw, Mustafa
SWH Author: Collins, Ian M.
Keywords: Cyclophosphamide
Nanoparticle
Breast Cancer
Issue Date: 2019
Date Accessioned: 2023-03-17T04:57:09Z
Date Available: 2023-03-17T04:57:09Z
Url: https://www.ncbi.nlm.nih.gov/pubmed/30763338
Format Startpage: e0210891
Source Volume: 14
Issue Number: 2
DOI: 10.1371/journal.pone.0210891
Abstract: This study evaluated the feasibility of achieving high response rates in stage II or III breast cancer by tailoring neoadjuvant therapy using clinical and histopathological features and the Oncotype DX Breast Recurrence Score. Genomic determinants of response and resistance were also explored. Fifty-one patients were enrolled. The primary cohort comprised 40 patients: 15 human epidermal growth factor receptor type 2 (HER2)-amplified; 15 triple-negative (TNBC); and ten hormone receptor (HR)-positive, HER2-non-amplified tumours; with recurrence scores ≥25. Patients were treated with epirubicin and cyclophosphamide, followed by nab-paclitaxel, with the addition of trastuzumab if HER2-amplified. The primary endpoint was pathological complete response (pCR) in the breast. Pre- and post-treatment tumour samples underwent variant burden, gene and gene pathway, mutational signature profile and clonal evolution analyses. The pCR rates were: overall 55% (n = 22), HER2-amplified 80% (n = 12), triple-negative 46% (n = 7) and HR-positive, HER2-non-amplified 30% (n = 3). Grade 3 or 4 adverse events included febrile neutropenia (8%), neutropenia (18%), sensory neuropathy (5%), deranged transaminases (5%), fatigue (2%), diarrhoea (2%), and pneumothorax (2%). Molecular analyses demonstrated strong similarities between residual disease and matched primary tumour. ATM signalling pathway alterations and the presence of a COSMIC Signature 3 implied the majority of tumours contained some form of homologous repair deficiency. ATM pathway alterations were identified in the subset of TNBC patients who did not achieve pCR; Signature 3 was present in both pCR and non-pCR subgroups. Clonal evolution analyses demonstrated both persistence and emergence of chemoresistant clones. This treatment regime resulted in a high rate of pCR, demonstrating that tailored neoadjuvant therapy using a genomic recurrence score is feasible and warrants further investigation. Molecular analysis revealed few commonalities between patients. For TNBC future clinical gains will require precision medicine, potentially using DNA sequencing to identify specific targets for individuals with resistant disease. Clinicaltrials.gov NCT01830244.
URI: https://repository.southwesthealthcare.com.au/swhealthcarejspui/handle/1/3476
Journal Title: PLOS ONE
Type: Journal Article
Appears in Collections:SWH Staff Publications



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