Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892043300> ?p ?o ?g. }
- W2892043300 endingPage "1403" @default.
- W2892043300 startingPage "1390" @default.
- W2892043300 abstract "CDK4/6 inhibition with endocrine therapy is now a standard of care for advanced estrogen receptor-positive breast cancer. Mechanisms of CDK4/6 inhibitor resistance have been described preclinically, with limited evidence from clinical samples. We conducted paired baseline and end-of-treatment circulating tumor DNA sequencing from 195 patients in the PALOMA-3 randomized phase III trial of palbociclib plus fulvestrant versus placebo plus fulvestrant. We show that clonal evolution occurs frequently during treatment, reflecting substantial subclonal complexity in breast cancer that has progressed after prior endocrine therapy. RB1 mutations emerged only in the palbociclib plus fulvestrant arm and in a minority of patients (6/127, 4.7%, P = 0.041). New driver mutations emerged in PIK3CA (P = 0.00069) and ESR1 after treatment in both arms, in particular ESR1 Y537S (P = 0.0037). Evolution of driver gene mutations was uncommon in patients progressing early on palbociclib plus fulvestrant but common in patients progressing later on treatment. These findings inform future treatment strategies to address resistance to palbociclib plus fulvestrant.Significance: Acquired mutations from fulvestrant are a major driver of resistance to fulvestrant and palbociclib combination therapy. ESR1 Y537S mutation promotes resistance to fulvestrant. Clonal evolution results in frequent acquisition of driver mutations in patients progressing late on therapy, which suggests that early and late progression have distinct mechanisms of resistance. Cancer Discov; 8(11); 1390-403. ©2018 AACR.See related commentary by Schiff and Jeselsohn, p. 1352This article is highlighted in the In This Issue feature, p. 1333." @default.
- W2892043300 created "2018-09-27" @default.
- W2892043300 creator A5001814176 @default.
- W2892043300 creator A5010278367 @default.
- W2892043300 creator A5018557915 @default.
- W2892043300 creator A5027068050 @default.
- W2892043300 creator A5032987754 @default.
- W2892043300 creator A5046214153 @default.
- W2892043300 creator A5047768231 @default.
- W2892043300 creator A5053473432 @default.
- W2892043300 creator A5056846110 @default.
- W2892043300 creator A5060044961 @default.
- W2892043300 creator A5075134210 @default.
- W2892043300 creator A5087559224 @default.
- W2892043300 creator A5091516461 @default.
- W2892043300 date "2018-11-01" @default.
- W2892043300 modified "2023-10-15" @default.
- W2892043300 title "The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial" @default.
- W2892043300 cites W2005895632 @default.
- W2892043300 cites W2006288875 @default.
- W2892043300 cites W2006352011 @default.
- W2892043300 cites W2015182193 @default.
- W2892043300 cites W2021145743 @default.
- W2892043300 cites W2053432671 @default.
- W2892043300 cites W2065388551 @default.
- W2892043300 cites W2096283457 @default.
- W2892043300 cites W2121098984 @default.
- W2892043300 cites W2121619780 @default.
- W2892043300 cites W2138601221 @default.
- W2892043300 cites W2148345265 @default.
- W2892043300 cites W2157852151 @default.
- W2892043300 cites W2161305430 @default.
- W2892043300 cites W2167278603 @default.
- W2892043300 cites W2171852242 @default.
- W2892043300 cites W2182664595 @default.
- W2892043300 cites W2276335691 @default.
- W2892043300 cites W2290950904 @default.
- W2892043300 cites W2309969893 @default.
- W2892043300 cites W2323851578 @default.
- W2892043300 cites W2329906190 @default.
- W2892043300 cites W2337209831 @default.
- W2892043300 cites W2375577403 @default.
- W2892043300 cites W2415372857 @default.
- W2892043300 cites W2514365970 @default.
- W2892043300 cites W2528767298 @default.
- W2892043300 cites W2537675006 @default.
- W2892043300 cites W2552099557 @default.
- W2892043300 cites W2560409587 @default.
- W2892043300 cites W2565436052 @default.
- W2892043300 cites W2565707423 @default.
- W2892043300 cites W2570752636 @default.
- W2892043300 cites W2592994249 @default.
- W2892043300 cites W2620993107 @default.
- W2892043300 cites W2621170119 @default.
- W2892043300 cites W2756005140 @default.
- W2892043300 cites W2763875663 @default.
- W2892043300 cites W2765435739 @default.
- W2892043300 cites W2771397989 @default.
- W2892043300 cites W779403461 @default.
- W2892043300 doi "https://doi.org/10.1158/2159-8290.cd-18-0264" @default.
- W2892043300 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6368247" @default.
- W2892043300 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30206110" @default.
- W2892043300 hasPublicationYear "2018" @default.
- W2892043300 type Work @default.
- W2892043300 sameAs 2892043300 @default.
- W2892043300 citedByCount "354" @default.
- W2892043300 countsByYear W28920433002018 @default.
- W2892043300 countsByYear W28920433002019 @default.
- W2892043300 countsByYear W28920433002020 @default.
- W2892043300 countsByYear W28920433002021 @default.
- W2892043300 countsByYear W28920433002022 @default.
- W2892043300 countsByYear W28920433002023 @default.
- W2892043300 crossrefType "journal-article" @default.
- W2892043300 hasAuthorship W2892043300A5001814176 @default.
- W2892043300 hasAuthorship W2892043300A5010278367 @default.
- W2892043300 hasAuthorship W2892043300A5018557915 @default.
- W2892043300 hasAuthorship W2892043300A5027068050 @default.
- W2892043300 hasAuthorship W2892043300A5032987754 @default.
- W2892043300 hasAuthorship W2892043300A5046214153 @default.
- W2892043300 hasAuthorship W2892043300A5047768231 @default.
- W2892043300 hasAuthorship W2892043300A5053473432 @default.
- W2892043300 hasAuthorship W2892043300A5056846110 @default.
- W2892043300 hasAuthorship W2892043300A5060044961 @default.
- W2892043300 hasAuthorship W2892043300A5075134210 @default.
- W2892043300 hasAuthorship W2892043300A5087559224 @default.
- W2892043300 hasAuthorship W2892043300A5091516461 @default.
- W2892043300 hasBestOaLocation W28920433001 @default.
- W2892043300 hasConcept C121608353 @default.
- W2892043300 hasConcept C126322002 @default.
- W2892043300 hasConcept C143998085 @default.
- W2892043300 hasConcept C2775930923 @default.
- W2892043300 hasConcept C2779744173 @default.
- W2892043300 hasConcept C2780482068 @default.
- W2892043300 hasConcept C530470458 @default.
- W2892043300 hasConcept C71924100 @default.
- W2892043300 hasConcept C84606932 @default.
- W2892043300 hasConceptScore W2892043300C121608353 @default.
- W2892043300 hasConceptScore W2892043300C126322002 @default.