000131667 001__ 131667
000131667 005__ 20241125101156.0
000131667 0247_ $$2doi$$a10.1158/1078-0432.CCR-23-0956
000131667 0248_ $$2sideral$$a137052
000131667 037__ $$aART-2023-137052
000131667 041__ $$aeng
000131667 100__ $$aPascual, Javier
000131667 245__ $$aBaseline mutations and ctDNA dynamics as prognostic and predictive factors in ER-positive/HER2-negative metastatic breast cancer patients
000131667 260__ $$c2023
000131667 5060_ $$aAccess copy available to the general public$$fUnrestricted
000131667 5203_ $$aPurpose: Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.
Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model.
Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms.
Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor–positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted.
000131667 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000131667 590__ $$a10.4$$b2023
000131667 592__ $$a4.623$$b2023
000131667 591__ $$aONCOLOGY$$b26 / 322 = 0.081$$c2023$$dQ1$$eT1
000131667 593__ $$aOncology$$c2023$$dQ1
000131667 593__ $$aCancer Research$$c2023$$dQ1
000131667 594__ $$a20.1$$b2023
000131667 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131667 700__ $$aGil-Gil, Miguel
000131667 700__ $$aProszek, Paula
000131667 700__ $$aZielinski, Christoph
000131667 700__ $$aReay, Alistair
000131667 700__ $$aRuiz-Borrego, Manuel
000131667 700__ $$aCutts, Rosalind
000131667 700__ $$aCiruelos Gil, Eva M.
000131667 700__ $$aFeber, Andrew
000131667 700__ $$aMuñoz-Mateu, Montserrat
000131667 700__ $$aSwift, Claire
000131667 700__ $$aBermejo, Begoña
000131667 700__ $$aHerranz, Jesus
000131667 700__ $$aMargeli Vila, Mireia
000131667 700__ $$0(orcid)0000-0002-9159-4988$$aAntón, Antonio$$uUniversidad de Zaragoza
000131667 700__ $$aKahan, Zsuzsanna
000131667 700__ $$aCsöszi, Tibor
000131667 700__ $$aLiu, Yuan
000131667 700__ $$aFernandez-Garcia, Daniel
000131667 700__ $$aGarcia-Murillas, Isaac
000131667 700__ $$aHubank, Michael
000131667 700__ $$aTurner, Nicholas C.
000131667 700__ $$aMartín, Miguel
000131667 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000131667 773__ $$g29, 20 (2023), 4166-4177$$pClin. cancer res.$$tCLINICAL CANCER RESEARCH$$x1078-0432
000131667 8564_ $$s5598434$$uhttps://zaguan.unizar.es/record/131667/files/texto_completo.pdf$$yVersión publicada
000131667 8564_ $$s3006326$$uhttps://zaguan.unizar.es/record/131667/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131667 909CO $$ooai:zaguan.unizar.es:131667$$particulos$$pdriver
000131667 951__ $$a2024-11-22-12:09:13
000131667 980__ $$aARTICLE