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Predictive modelling of response to neoadjuvant therapy in HER2+ breast cancer.
Cosgrove, Nicola; Eustace, Alex J; O'Donovan, Peter; Madden, Stephen F; Moran, Bruce; Crown, John; Moulton, Brian; Morris, Patrick G; Grogan, Liam; Breathnach, Oscar; Power, Colm; Allen, Michael; Walshe, Janice M; Hill, Arnold D; Blümel, Anna; O'Connor, Darren; Das, Sudipto; Milewska, Malgorzata; Fay, Joanna; Kay, Elaine; Toomey, Sinead; Hennessy, Bryan T; Furney, Simon J.
Affiliation
  • Cosgrove N; Genomic Oncology Research Group, Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Eustace AJ; School of Biotechnology, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
  • O'Donovan P; Genomic Oncology Research Group, Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Madden SF; Data Science Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Moran B; Conway Institute, University College Dublin, Dublin, Ireland.
  • Crown J; Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.
  • Moulton B; Clinical Oncology Development Europe, Dublin, Ireland.
  • Morris PG; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
  • Grogan L; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
  • Breathnach O; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.
  • Power C; Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Allen M; Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Walshe JM; Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.
  • Hill AD; Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Blümel A; School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • O'Connor D; School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Das S; School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
  • Milewska M; Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, 9, Ireland.
  • Fay J; RCSI Biobank Service, RCSI University of Medicine and Health Sciences, Beaumont Hospital, Dublin, 9, Ireland.
  • Kay E; Department of Pathology, RCSI University of Medicine and Health Sciences, Beaumont Hospital, Dublin, 9, Ireland.
  • Toomey S; Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, 9, Ireland.
  • Hennessy BT; Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland. bryanhennessy@rcsi.ie.
  • Furney SJ; Medical Oncology Group, Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, 9, Ireland. bryanhennessy@rcsi.ie.
NPJ Breast Cancer ; 9(1): 72, 2023 Sep 27.
Article in En | MEDLINE | ID: mdl-37758711
HER2-positive (HER2+) breast cancer accounts for 20-25% of all breast cancers. Predictive biomarkers of neoadjuvant therapy response are needed to better identify patients with early stage disease who may benefit from tailored treatments in the adjuvant setting. As part of the TCHL phase-II clinical trial (ICORG10-05/NCT01485926) whole exome DNA sequencing was carried out on normal-tumour pairs collected from 22 patients. Here we report predictive modelling of neoadjuvant therapy response using clinicopathological and genomic features of pre-treatment tumour biopsies identified age, estrogen receptor (ER) status and level of immune cell infiltration may together be important for predicting response. Clonal evolution analysis of longitudinally collected tumour samples show subclonal diversity and dynamics are evident with potential therapy resistant subclones detected. The sources of greater pre-treatment immunogenicity associated with a pathological complete response is largely unexplored in HER2+ tumours. However, here we point to the possibility of APOBEC associated mutagenesis, specifically in the ER-neg/HER2+ subtype as a potential mediator of this immunogenic phenotype.

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies / Risk_factors_studies Language: En Journal: NPJ Breast Cancer Year: 2023 Type: Article Affiliation country: Ireland

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies / Risk_factors_studies Language: En Journal: NPJ Breast Cancer Year: 2023 Type: Article Affiliation country: Ireland