{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T04:37:07Z","timestamp":1793507827976,"version":"4.5.0"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Cross-talk between signal transduction pathways likely contributes to hormone resistance in metastatic breast cancer (mBC). Everolimus, an oral inhibitor of the mammalian target of rapamycin, has restored sensitivity in endocrine-resistance models and shown anticancer activity in early-phase mBC clinical trials. This analysis evaluated efficacy and safety of everolimus in combination with tamoxifen in patients with mBC resistant to aromatase inhibitors (AIs). <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> This open-label, phase II study randomly assigned postmenopausal women with hormone receptor\u2013positive, human epidermal growth factor receptor 2\u2013negative, AI-resistant mBC to tamoxifen 20 mg\/d plus everolimus 10 mg\/d (n = 54) or tamoxifen 20 mg\/d alone (n = 57). Randomization was stratified by primary and secondary hormone resistance. Primary end point was clinical benefit rate (CBR), defined as the percentage of all patients with a complete or partial response or stable disease at 6 months. No formal statistical comparison between groups was planned. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> The 6-month CBR was 61% (95% CI, 47 to 74) with tamoxifen plus everolimus and 42% (95% CI, 29 to 56) with tamoxifen alone. Time to progression (TTP) increased from 4.5 months with tamoxifen alone to 8.6 months with tamoxifen plus everolimus, corresponding to a 46% reduction in risk of progression with the combination (hazard ratio [HR], 0.54; 95% CI, 0.36 to 0.81). Risk of death was reduced by 55% with tamoxifen plus everolimus versus tamoxifen alone (HR, 0.45; 95% CI, 0.24 to 0.81). The main toxicities associated with tamoxifen plus everolimus were fatigue (72% v 53% with tamoxifen alone), stomatitis (56% v 7%), rash (44% v 7%), anorexia (43% v 18%), and diarrhea (39% v 11%). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> This study suggests that tamoxifen plus everolimus increased CBR, TTP, and overall survival compared with tamoxifen alone in postmenopausal women with AI-resistant mBC. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2011.39.0708","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T07:18:05Z","timestamp":1336461485000},"page":"2718-2724","source":"Crossref","is-referenced-by-count":599,"title":["Randomized Phase II Trial of Everolimus in Combination With Tamoxifen in Patients With Hormone Receptor\u2013Positive, Human Epidermal Growth Factor Receptor 2\u2013Negative Metastatic Breast Cancer With Prior Exposure to Aromatase Inhibitors: A GINECO Study"],"prefix":"10.1200","volume":"30","author":[{"given":"Thomas","family":"Bachelot","sequence":"first","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Bourgier","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Cropet","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Ray-Coquard","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Freyer","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Abadie-Lacourtoisie","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Eymard","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Debled","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Spa\u00ebth","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Legouffe","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djelila","family":"Allouache","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"El Kouri","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pujade-Lauraine","sequence":"additional","affiliation":[{"name":"Thomas Bachelot, Claire Cropet, and Isabelle Ray-Coquard, Universit\u00e9 Lyon 1, Centre L\u00e9on B\u00e9rard, Lyon; C\u00e9line Bourgier, Institut Gustave Roussy, Villejuif; Jean-Marc Ferrero, Centre Antoine Lacassagne, Nice; Gilles Freyer, Centre Hospitalier Lyon Sud, Pierre-B\u00e9nite; Sophie Abadie-Lacourtoisie, Centre Paul Papin, Angers; Jean-Christophe Eymard, Institut Jean Godinot, Reims; Marc Debled, Institut Bergoni\u00e9, Bordeaux; Dominique Spa\u00ebth, Centre d'Oncologie de Gentilly, Nancy; Eric Legouffe, Clinique de..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.22.3758"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2006.01.007"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.194"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.5822"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2007.05.008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41680"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2005.04.025"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0035"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-2402"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm170"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.21.3033"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.0988"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.5482"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2007.10.003"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.18.8391"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(89)90015-9"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(03)00602-6"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.10.8407"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1823"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.12.019"},{"key":"B23","volume-title":"Presented at the 29th Annual San Antonio Breast Cancer Symposium","author":"Chow LWC"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109653"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009290"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61039-9"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1001671"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2011.39.0708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T22:25:33Z","timestamp":1653517533000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2011.39.0708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,1]]},"references-count":26,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2012,8,1]]}},"alternative-id":["10.1200\/JCO.2011.39.0708"],"URL":"https:\/\/doi.org\/10.1200\/jco.2011.39.0708","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,1]]}}}