{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:36:29Z","timestamp":1714696589588},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","issue":"9_Supplement","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background<\/jats:p>\n               <jats:p>Cyclin Dependent Kinase inhibitors (CDKi\u2019s) in combination with Endocrine Therapy (ET) have changed the first line management of patients with the most common subtype (HR+, HER2-) of metastatic breast cancer (MBC), improving progression-free survival (PFS) and overall survival.<\/jats:p>\n               <jats:p>However, in approved indications for advanced breast cancer, approximately 20% of patients have been observed to have no response to CDKi\u2019s and ET, and to progress after starting these therapies. Unlike other targeted therapeutics, there is no companion diagnostic or other clinically reliable biomarker for clinical decision support to indicate which patients will and will not benefit from CDKi therapy.<\/jats:p>\n               <jats:p>Methods<\/jats:p>\n               <jats:p>We have developed a novel platform that measures the Immune Activation Signature of patient plasma samples. Via simple measurements of the total concentration of protein-incorporated amino acid residues within patient plasma samples, the platform is designed to reveal changes in the proportion of immunoglobulins and albumin, and class-switching among immunoglobulins. For that purpose, we use Bioorthogonal chemical labelling reactions to label the protein-incorporated amino acids residues within the plasma.<\/jats:p>\n               <jats:p>We measured the plasma samples of N=30 HR+, HER2- MBC patients, median age 54 years old, who were baseline na\u00efve for CDKi\u2019s treatment (16 on palbociclib, 11 on ribociclib, and 3 on abemaciclib) and ET.<\/jats:p>\n               <jats:p>Eighteen patients had metastatic visceral disease and 12 patients had bone-only MBC. All patients were prospectively followed, and response assessed according to RECIST criteria on a CT scan every 3-months.<\/jats:p>\n               <jats:p>Results<\/jats:p>\n               <jats:p>Non-responding patients developed objective progressive disease during the first 6 months after starting CDKis and ET. In this cohort, 4 patients (13%) were classified as non-responders.<\/jats:p>\n               <jats:p>The median PFS in non-responding patients was 4.5 months (4.03-5.02) and the median PFS in the cohort of responding patients was 16.6 months (6.8 \u2013 40.9). The Immune Activation Signatures of the Responding and Non-Responding patients are shown in table 1.<\/jats:p>\n               <jats:p>We analyzed the results with classical statistics and machine learning. A multivariate analysis of variance (MANOVA) test of the null hypothesis that the Immune Activation Signatures of Non-Responders and Responders are the same gave p = 0.00388.<\/jats:p>\n               <jats:p>We analyzed the measured Immune Activation Signatures using a supervised machine learning classifier and observed in a held-back validation set correct prediction of 100% of non-responding patients and 95% accurate predictions overall.<\/jats:p>\n               <jats:p>Conclusions<\/jats:p>\n               <jats:p>According to these results, this platform may provide a clinically helpful biomarker for clinical decision support in the advanced or aggressive breast cancer context (patients with visceral metastasis bordering on visceral crisis), or for patient stratification in new indications.<\/jats:p>\n               <jats:p>Table. Immune Activation Signature measurements (mean values in Clinical Outcome)<\/jats:p>\n               <jats:p>Citation Format: Luis Costa, Cong Tang, Emma Yates, Qi Shi, Wesley Sukdao, Patricia Corredeira, Gon\u00e7alo Costa, Helena Pais, Catarina Abreu, Leonor Ribeiro, Rita Teixeira de Sousa, Sofia Torres, Andr\u00e9 Mansinho, Sandra Casimiro, Ana Cavaco, Patricia Alves, Angela Rodrigues, Lisiana Szeneszi, Gon\u00e7alo Bernardes. Immune Activation Signatures for predicting CDKi primary response in advanced breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-05.<\/jats:p>","DOI":"10.1158\/1538-7445.sabcs23-po4-05-05","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T07:11:10Z","timestamp":1714633870000},"page":"PO4-05-05-PO4-05-05","update-policy":"http:\/\/dx.doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Abstract PO4-05-05: Immune Activation Signatures for predicting CDKi primary response in advanced breast cancer patients"],"prefix":"10.1158","volume":"84","author":[{"given":"Luis","family":"Costa","sequence":"first","affiliation":[{"name":"1Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, Lisboa, Portugal;"}]},{"given":"Cong","family":"Tang","sequence":"additional","affiliation":[{"name":"2Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisboa, Portugal.;"}]},{"given":"Emma","family":"Yates","sequence":"additional","affiliation":[{"name":"3Proteotype Diagnostics Ltd;"}]},{"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"4Data Science Knowledge Center, Nova School of Business and Economics, Carcavelos, Portugal;"}]},{"given":"Wesley","family":"Sukdao","sequence":"additional","affiliation":[{"name":"3Proteotype Diagnostics Ltd;"}]},{"given":"Patricia","family":"Corredeira","sequence":"additional","affiliation":[{"name":"5Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal.;"}]},{"given":"Gon\u00e7alo","family":"Costa","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Helena","family":"Pais","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Catarina","family":"Abreu","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Leonor","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Rita Teixeira","family":"de Sousa","sequence":"additional","affiliation":[{"name":"7Hospital of Santa Maria, Lisbon, Portugal;"}]},{"given":"Sofia","family":"Torres","sequence":"additional","affiliation":[{"name":"8Centro Hospitalar Lisboa Norte, Portugal;"}]},{"given":"Andr\u00e9","family":"Mansinho","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Sandra","family":"Casimiro","sequence":"additional","affiliation":[{"name":"5Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal.;"}]},{"given":"Ana","family":"Cavaco","sequence":"additional","affiliation":[{"name":"5Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal.;"}]},{"given":"Patricia","family":"Alves","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Angela","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Lisiana","family":"Szeneszi","sequence":"additional","affiliation":[{"name":"6Oncology Division, Hospital de Santa Maria, Centro Hospitalar Universit\u00e1rio Lisboa Norte, 1649-028 Lisbon, Portugal.;"}]},{"given":"Gon\u00e7alo","family":"Bernardes","sequence":"additional","affiliation":[{"name":"9Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom. Instituto de Medicina Molecular Jo\u00e3o Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, 1649-028 Lisbon, Portugal."}]}],"member":"1086","container-title":["Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/84\/9_Supplement\/PO4-05-05\/744174\/Abstract-PO4-05-05-Immune-Activation-Signatures","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/84\/9_Supplement\/PO4-05-05\/744174\/Abstract-PO4-05-05-Immune-Activation-Signatures","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T07:11:12Z","timestamp":1714633872000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/84\/9_Supplement\/PO4-05-05\/744174\/Abstract-PO4-05-05-Immune-Activation-Signatures"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,2]]},"references-count":0,"journal-issue":{"issue":"9_Supplement","published-print":{"date-parts":[[2024,5,2]]}},"URL":"https:\/\/doi.org\/10.1158\/1538-7445.sabcs23-po4-05-05","relation":{},"ISSN":["1538-7445"],"issn-type":[{"value":"1538-7445","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,2]]}}}