000086498 001__ 86498 000086498 005__ 20200221144241.0 000086498 0247_ $$2doi$$a10.1093/annonc/mdw363.83 000086498 0248_ $$2sideral$$a106291 000086498 037__ $$aART-2016-106291 000086498 041__ $$aeng 000086498 100__ $$aHaba, J. de la 000086498 245__ $$aACE and CXCL10 as predictive biomarkers in the LEA study 000086498 260__ $$c2016 000086498 5060_ $$aAccess copy available to the general public$$fUnrestricted 000086498 5203_ $$aBackground: LEA Study (GEICAM/2006-11/GBG51), is a randomized clinical trial comparing bevacizumab in combination with endocrine therapy (ET + B) with endocrine therapy (ET) in postmenopausal women with advanced or metastatic HR-positive/HER2-negative breast cancer (BC) with indication of hormonotherapy as first-line treatment. Patients with secondary hypertension had better progression-free survival (PFS) and overall survival (OS). We have evaluated the role of two hypertension-related biomarkers, Angiotensin-Converting Enzyme (ACE) and Small-Inducible Cytokine B10 (CXCL10) as prognostic and/or predictive biomarkers of benefit to bevacizumab in the first line metastatic disease. Methods: From 380 patients, 266 were included in 33 Spanish sites. Median age was 64 years, 63.5% had measurable disease, 97.4% were metastatic at randomization, 51.5% had visceral disease and 52.6% received previous chemotherapy. PFS was 14.3 months (range 0.8-61.1), OS was 34 months (range 0.8-71.6) and 93 patients had Objective Response (OR). We analyzed 124 plasma samples collected before treatment (52 from ET and 72 from ET + B arms). Circulating levels of ACE and CXCL10 were determined by ELISA. ACE levels of 115ng/ml and 135ng/ml were pre-defined as cutoff values. CXCL10 was explored as a quantitative variable. Results: PFS was 15.1 months (range 1.4-61.1), OS was 31.1 months (range 2.8-61.1) and 40.3% had OR. OR was significantly different between treatment arms (p < 0.001) but not PFS or OS. Median ACE concentration was 130.9ng/ml (range 35.3-315.4). Low ACE (<135ng/ml) had better PFS in the whole population (p = 0.048) and in the ET + B arm (p = 0.041). ACE cutoff of 115 ng/ml was not able to identify any subgroup with better prognosis. Median CXCL10 concentration was 230.3pg/ml (range 15.1-4129.6). A higher expression of CXCL10 was significantly associated with worse OS in the whole population (p < 0.0001) and each treatment arm (p = 0.002 and p = 0.001 in ET and ET + B, respectively). No association with OR were identified neither for ACE nor for CXCL10. Conclusions: ACE levels could be considered a prognostic and a bevacizumab predictive biomarker of PFS. CXCL10 could be prognostic of OS. Confirmatory studies are warranted. 000086498 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/ 000086498 590__ $$a11.855$$b2016 000086498 591__ $$aONCOLOGY$$b10 / 217 = 0.046$$c2016$$dQ1$$eT1 000086498 592__ $$a5.096$$b2016 000086498 593__ $$aHematology$$c2016$$dQ1 000086498 593__ $$aOncology$$c2016$$dQ1 000086498 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1 000086498 655_4 $$ainfo:eu-repo/semantics/conferenceObject$$vinfo:eu-repo/semantics/publishedVersion 000086498 700__ $$aAguilar, E. Aranda 000086498 700__ $$aMorales, S. 000086498 700__ $$aGarcía-Sáenz, J.A. 000086498 700__ $$aGuerrero, A. 000086498 700__ $$aMartínez, N. 000086498 700__ $$0(orcid)0000-0002-9159-4988$$aAntón, A.$$uUniversidad de Zaragoza 000086498 700__ $$aMuñoz, M. 000086498 700__ $$aRamos, M. 000086498 700__ $$aGil-Gil, M. 000086498 700__ $$aMargelí, M. 000086498 700__ $$aServitja, S. 000086498 700__ $$aBermejo, B. 000086498 700__ $$aCruz, J. 000086498 700__ $$aLescure, A. Rodríguez 000086498 700__ $$aCasas, M. 000086498 700__ $$aSánchez-Aragó, M. 000086498 700__ $$aCaballero, R. 000086498 700__ $$aCarrasco, E. 000086498 700__ $$aMartin, M. 000086498 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000086498 773__ $$g27, Suppl. 6 (2016), [135P] vi41$$pAnn. oncol.$$tANNALS OF ONCOLOGY$$x0923-7534 000086498 8564_ $$s36280$$uhttps://zaguan.unizar.es/record/86498/files/texto_completo.pdf$$yVersión publicada 000086498 8564_ $$s59823$$uhttps://zaguan.unizar.es/record/86498/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000086498 909CO $$ooai:zaguan.unizar.es:86498$$particulos$$pdriver 000086498 951__ $$a2020-02-21-13:21:49 000086498 980__ $$aARTICLE