التفاصيل البيبلوغرافية
| العنوان: |
HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer |
| المؤلفون: |
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 |
| المصدر: |
eBioMedicine , Article 104205. (2022) (In press). |
| بيانات النشر: |
Elsevier BV |
| سنة النشر: |
2022 |
| المجموعة: |
University College London: UCL Discovery |
| مصطلحات موضوعية: |
Breast cancer, HER2+, Aromatase inhibitors, HER2-Enriched subtype |
| الوصف: |
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<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
text |
| اللغة: |
English |
| العلاقة: |
https://discovery.ucl.ac.uk/id/eprint/10154096/1/1-s2.0-S2352396422003875-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10154096Test/ |
| الإتاحة: |
https://discovery.ucl.ac.uk/id/eprint/10154096/1/1-s2.0-S2352396422003875-main.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10154096Test/ |
| حقوق: |
open |
| رقم الانضمام: |
edsbas.EAA26255 |
| قاعدة البيانات: |
BASE |
