| Title: |
HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer |
| Authors: |
Bergamino, Milana A; López-Knowles, Elena; Morani, Gabriele; Tovey, Holly; Kilburn, Lucy; Schuster, Eugene F; Alataki, Anastasia; Hills, Margaret; Xiao, Hui; Holcombe, Chris; Skene, Anthony; Robertson, John F; Smith, Ian E; Bliss, Judith M; Dowsett, Mitch; Cheang, Maggie CU; Evans, Abigail; Ball, Adrian; Johri, Akhil; Nejim, Ali; Jones, Alison; Corder, Allan; Thorne, Amanda; Anand, Ambika; Chakrabarti, Amitabha; Robinson, Anne; Modi, Anupam; Patel, Ashraf; Kothari, Ashutosh; McFall, Brendan; Mortimer, Caroline; Lee, Caroline; Chan, Charlie; Abson, Charlotte; Holcombe, Christopher; Hinton, Christopher; Hollywood, Ciaran; Murphy, Claire; Crowley, Clare; Harding-Mackean, Claudia; Griffith, Clive; Lewanski, Conrad; Rea, Daniel; Hwang, David; Crawford, Derek; Thekkinkattil, Dinesh; Ferguson, Douglas; Adamson, Douglas; Wheatley, Duncan; Ravichandran, Duraisamy; Babu, Ed; Hyett, Elaine; Ashkanani, Fawzia; Hoar, Fiona; Kenny, Frances; Dyke, Gary; Sparrow, Geoffrey; Gilbert, .; Cunnick, Giles; Algurafi, Hafiz; Sweetland, Helen; Prof, Highes-Davies; Hamed, Hisham; Smith, Ian; Laidlaw, Ian; Khattak, Ilyas; Newby, Jacqueline; Rees-Lee, Jacqueline; Kokan, Jalal; Barrett, Jane; Naik, Jay Dolatrai; Vaidya, Jayant; Forrest, Jennifer; Parmar, Jitendra; Adams, Jocelyn; Fox, John; Roberts, Jonathan; Dawson, Jonathan; Doughty, Julie; Donnelly, Jull; Dunn, Kathleen; Chin, Kian; Horgan, Kieran; Thakur, Kislaya; Barthelmes, Ludger; Wyld, Lynda; Bhattacharyya, Madhumita; Hadaki, Maher; Kishore, Makam; Ornstein, Marcus; Bramley, Maria; Bews-Hair, Maria; Parton, Marina; Sibbering, Mark; Kissin, Mark; Churn, Mark; Hogg, Martin; Quigley, Mary; Hatton, Matthew; Winter, Matthew; Adelekan, Matthew; Shere, Michael; Carr, Michael; Williams, Michael; Absar, Mohammed; Sharif, Muhammad; Kelleher, Muireann; Walji, Nawaz; Williams, Nicholas; Gallegos, Nicholas; Bundred, Nigel; Hatcher, Olivia; Crellin, Perric; Crane, Peter; Donnelly, Peter; Kneeshaw, Peter; Walker, Philip; Sinha, Prakash; Bhaskar, Pudhupalayam; Soulsby, Racheal; Todd, Radha; Vidya, Raghavan; Mehra, Rakesh; Prasad, Ramachandran; Cutress, Ramsay; Sharma, Ravi; Roylance, Rebecca; Goranova, Rebecca; Salman, Reem Ramzi; Bonom, Riccardo; Johnson, Richard; Sutton, Richard; Linforth, Rick; Coleman, Rob; Grieve, Robert; Leonard, Robert; Reichert, Robert; Kennedy, Robert; Agarwal, Roshan; Allerton, Rozenn; Burcombe, Russell; Davis, Ruth; Narayanan, Sankaran; Chandrasekharan, Sankaran; Vesty, Sarah; Seetharam, Seema; Ledwidge, Serena; Iqbal, Shabana; Wahee, Shamaela; Silva, Shobha; Pain, Simon; Holt, Simon; Thomson, Simon; Smith, Simon; Ellenbogen, Simon; Laws, Siobhan; Chan, Stephen; Johnston, Stephen; Holt, Steve; Thrush, Steven; McIntosh, Stuart; Chatterjee, Sumohan; Cleator, Susan; Usman, Tamoor; Johnson, Tayo; Kovacs, Tibor; Irvine, Tracey; Barthkur, Urmila; Pope, Vanessa; Brown, Victoria Alexandra; Muralikrishna, Vummiti; Samra, Walid; Maxwell, William; Winters, Zoe |
| Source: |
eBioMedicine , Article 104205. (2022) (In press). |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2022 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Breast cancer; HER2+; Aromatase inhibitors; HER2-Enriched subtype |
| Description: |
BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10154096/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10154096/1/1-s2.0-S2352396422003875-main.pdf; https://discovery.ucl.ac.uk/id/eprint/10154096/ |
| Rights: |
open |
| Accession Number: |
edsbas.EAA26255 |
| Database: |
BASE |