| Added by | standudu |
|---|---|
| Group name | EquipeCTCS |
| Item Type | Journal Article |
| Title | ER+, HER2- advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes |
| Creator | Chen et al. |
| Author | Jessica W. Chen |
| Author | William Jacot |
| Author | Javier Cortés |
| Author | Ian E. Krop |
| Author | Susan Dent |
| Author | Nadia Harbeck |
| Author | Michelino De Laurentiis |
| Author | Young-Hyuck Im |
| Author | Thomas J. Stout |
| Author | Frauke Schimmoller |
| Author | Heidi M. Savage |
| Author | Katherine E. Hutchinson |
| Author | Timothy R. Wilson |
| Abstract | Taselisib is a potent ?-sparing phosphatidylinositol 3-kinase (PI3K) inhibitor that, with endocrine therapy, improves outcomes in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated (PIK3CAmut) advanced breast cancer. To understand alterations associated with response to PI3K inhibition, we analysed circulating tumour DNA (ctDNA) from participants enrolled in the SANDPIPER trial. Participants were designated as either PIK3CAmut or PIK3CA no mutation was detected (NMD) per baseline ctDNA. The top mutated genes and tumour fraction estimates identified were analysed for their association with outcomes. In participants with PIK3CAmut ctDNA treated with taselisib?+?fulvestrant, tumour protein p53 (TP53; encoding p53) and fibroblast growth factor receptor 1 (FGFR1) alterations were associated with shorter progression-free survival (PFS) compared to participants with NMD in these genes. Conversely, participants with PIK3CAmut ctDNA harbouring a neurofibromin 1 (NF1) alteration or high baseline tumour fraction estimate experienced improved PFS upon treatment with taselisib?+?fulvestrant compared to placebo?+?fulvestrant. Broadly, alterations in oestrogen receptor (ER), PI3K and p53 pathway genes were associated with resistance to taselisib?+?fulvestrant in participants with PIK3CAmut ctDNA. Altogether, we demonstrated the impact of genomic (co-)alterations on outcomes with one of the largest clinico-genomic datasets of ER+, HER2-, PIK3CAmut breast cancer patients treated with a PI3K inhibitor. |
| Publication | Molecular Oncology |
| Volume | 17 |
| Issue | 10 |
| Pages | 2000-2016 |
| Date | 2023-10 |
| Journal Abbr | Mol Oncol |
| Language | eng |
| DOI | 10.1002/1878-0261.13416 |
| ISSN | 1878-0261 |
| Short Title | ER+, HER2- advanced breast cancer treated with taselisib and fulvestrant |
| Library Catalog | PubMed |
| Extra | PMID: 36892268 PMCID: PMC10552898 |
| Tags | Antineoplastic Combined Chemotherapy Protocols, breast cancer, Breast Neoplasms, circulating tumour DNA, Class I Phosphatidylinositol 3-Kinases, clinic, Female, Fulvestrant, Genomics, Humans, Phosphatidylinositol 3-Kinases, PIK3CA, Receptor, ErbB-2, Receptors, Estrogen, SANDPIPER, taselisib, Tumor Suppressor Protein p53 |
| Date Added | 2023/10/16 - 16:16:43 |
| Date Modified | 2023/10/16 - 17:20:08 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
