{"id":{"repo_id":"milano","oai_identifier":"oai:air.unimi.it:2434/1119775"},"canonical_url":"https://search.dev.ndltd.org/etd/milano/oai:air.unimi.it:2434/1119775","repository":{"repo_id":"milano","name":"Università degli Studi di Milano","base_url":"https://air.unimi.it/oai/request"},"display":{"title":"ANTIBODY-DRUG CONJUGATES FOR THE TREATMENT OF BREAST CANCER.","abstract":"Background: Trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are anti-HER2 antibody-drug conjugates (ADCs) which have shown robust efficacy for treating breast cancer. For both ADCs, however, we lack effective biomarkers to predict outcomes from pre-treatment samples. Methods: To unveil predictive biomarkers for ADCs, we first evaluated 5-year outcomes in a prospective trial (ATEMPT) testing adjuvant T-DM1 in patients with stage I HER2+ breast cancer, and reviewed real-world outcomes with T-DXd for patients with metatatic breast cancer at two academic institutions. Moreover, we conducted a multi-omic assessment of HER2 and extensive translational analyses to predict outcomes with T-DM1 in ATEMPT and T-DXd in the real world. Results: Among 383 patients with stage I HER2+ breast cancer receiving adjuvant T-DM1, the 5-year iDFS was 97.0% (95% CI, 95.2 to 98.7). For those patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes differed according to HER2DX risk score, with significantly better RFI and iDFS among patients with HER2DX low-risk versus high-risk tumors. We also evaluated real-world outcomes among 191 patients with metastatic breast cancer. Herein, we demonstrate that T-DXd is associated with relevant real-world activity, with a time-to-next treatment of 9.1 months (range: 7.6 – 10.4) and an overall survival of 22.2 months (range: 17.1 – 25.2). The quantitative proteomic (High Sensitivity-HER2, Reverse Phase Protein Array), transcriptomic (HER2DX) and circulating tumor DNA (DNADX) assessment of HER2 on pre-T-DXd samples enabled a refined prediction of T-DXd efficacy, including in subgroup analyses of HER2-positive and HER2-negative breast cancer. Conclusion: a multi-omic characterization of HER2 expression in pre-treatment tumor samples showed promise in predicting the efficacy of T-DM1 in an adjuvant trial and T-DXd in the real world. Further validation of the biomarkers included in this study is planned within three ongoing phase 2 clinical trials, and may lead in the future to a refined use of anti-HER2 ADCs in clinical practice.","abstract_html":"Background: Trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are anti-HER2 antibody-drug conjugates (ADCs) which have shown robust efficacy for treating breast cancer. For both ADCs, however, we lack effective biomarkers to predict outcomes from pre-treatment samples. Methods: To unveil predictive biomarkers for ADCs, we first evaluated 5-year outcomes in a prospective trial (ATEMPT) testing adjuvant T-DM1 in patients with stage I HER2+ breast cancer, and reviewed real-world outcomes with T-DXd for patients with metatatic breast cancer at two academic institutions. Moreover, we conducted a multi-omic assessment of HER2 and extensive translational analyses to predict outcomes with T-DM1 in ATEMPT and T-DXd in the real world. Results: Among 383 patients with stage I HER2+ breast cancer receiving adjuvant T-DM1, the 5-year iDFS was 97.0% (95% CI, 95.2 to 98.7). For those patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes differed according to HER2DX risk score, with significantly better RFI and iDFS among patients with HER2DX low-risk versus high-risk tumors. We also evaluated real-world outcomes among 191 patients with metastatic breast cancer. Herein, we demonstrate that T-DXd is associated with relevant real-world activity, with a time-to-next treatment of 9.1 months (range: 7.6 – 10.4) and an overall survival of 22.2 months (range: 17.1 – 25.2). The quantitative proteomic (High Sensitivity-HER2, Reverse Phase Protein Array), transcriptomic (HER2DX) and circulating tumor DNA (DNADX) assessment of HER2 on pre-T-DXd samples enabled a refined prediction of T-DXd efficacy, including in subgroup analyses of HER2-positive and HER2-negative breast cancer. Conclusion: a multi-omic characterization of HER2 expression in pre-treatment tumor samples showed promise in predicting the efficacy of T-DM1 in an adjuvant trial and T-DXd in the real world. Further validation of the biomarkers included in this study is planned within three ongoing phase 2 clinical trials, and may lead in the future to a refined use of anti-HER2 ADCs in clinical practice.","abstract_has_math":false,"creators":["TARANTINO, PAOLO"],"institution":"Università degli Studi di Milano","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["tutor: G. Curigliano ; co-tutor: S. Tolaney ; revisori: P. Lorusso","F. Andre' ; coordinatore: M. Del Fabbro","P. Tarantino","CURIGLIANO, GIUSEPPE","DEL FABBRO, MASSIMO"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-12-19","date_published":"2024-12-19","updated_at":"2026-07-27T20:18:51Z","subjects":["Settore MED/50 - Scienze Tecniche Mediche Applicate"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dx.doi.org/10.13130/tarantino-paolo_phd2024-12-19","10.13130/tarantino-paolo_phd2024-12-19"],"render_values":[{"text":"http://dx.doi.org/10.13130/tarantino-paolo_phd2024-12-19","href":"http://dx.doi.org/10.13130/tarantino-paolo_phd2024-12-19","code":true},{"text":"10.13130/tarantino-paolo_phd2024-12-19","href":"https://doi.org/10.13130/tarantino-paolo_phd2024-12-19","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2434/1119775","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["tutor: G. 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For both ADCs, however, we lack effective biomarkers to predict outcomes from pre-treatment samples. Methods: To unveil predictive biomarkers for ADCs, we first evaluated 5-year outcomes in a prospective trial (ATEMPT) testing adjuvant T-DM1 in patients with stage I HER2+ breast cancer, and reviewed real-world outcomes with T-DXd for patients with metatatic breast cancer at two academic institutions. Moreover, we conducted a multi-omic assessment of HER2 and extensive translational analyses to predict outcomes with T-DM1 in ATEMPT and T-DXd in the real world. Results: Among 383 patients with stage I HER2+ breast cancer receiving adjuvant T-DM1, the 5-year iDFS was 97.0% (95% CI, 95.2 to 98.7). For those patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes differed according to HER2DX risk score, with significantly better RFI and iDFS among patients with HER2DX low-risk versus high-risk tumors. We also evaluated real-world outcomes among 191 patients with metastatic breast cancer. Herein, we demonstrate that T-DXd is associated with relevant real-world activity, with a time-to-next treatment of 9.1 months (range: 7.6 – 10.4) and an overall survival of 22.2 months (range: 17.1 – 25.2). The quantitative proteomic (High Sensitivity-HER2, Reverse Phase Protein Array), transcriptomic (HER2DX) and circulating tumor DNA (DNADX) assessment of HER2 on pre-T-DXd samples enabled a refined prediction of T-DXd efficacy, including in subgroup analyses of HER2-positive and HER2-negative breast cancer. Conclusion: a multi-omic characterization of HER2 expression in pre-treatment tumor samples showed promise in predicting the efficacy of T-DM1 in an adjuvant trial and T-DXd in the real world. Further validation of the biomarkers included in this study is planned within three ongoing phase 2 clinical trials, and may lead in the future to a refined use of anti-HER2 ADCs in clinical practice."]},{"key":"dc:title","label":"Title","values":["ANTIBODY-DRUG CONJUGATES FOR THE TREATMENT OF BREAST CANCER."]}]}],"canonical_facts":{"dc:contributor":["tutor: G. Curigliano ; co-tutor: S. Tolaney ; revisori: P. Lorusso","F. Andre' ; coordinatore: M. Del Fabbro","P. Tarantino","CURIGLIANO, GIUSEPPE","DEL FABBRO, MASSIMO"],"dc:creator":["TARANTINO, PAOLO"],"dc:date":["2024-12-19"],"dc:description":["Background: Trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) are anti-HER2 antibody-drug conjugates (ADCs) which have shown robust efficacy for treating breast cancer. For both ADCs, however, we lack effective biomarkers to predict outcomes from pre-treatment samples. Methods: To unveil predictive biomarkers for ADCs, we first evaluated 5-year outcomes in a prospective trial (ATEMPT) testing adjuvant T-DM1 in patients with stage I HER2+ breast cancer, and reviewed real-world outcomes with T-DXd for patients with metatatic breast cancer at two academic institutions. Moreover, we conducted a multi-omic assessment of HER2 and extensive translational analyses to predict outcomes with T-DM1 in ATEMPT and T-DXd in the real world. Results: Among 383 patients with stage I HER2+ breast cancer receiving adjuvant T-DM1, the 5-year iDFS was 97.0% (95% CI, 95.2 to 98.7). For those patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes differed according to HER2DX risk score, with significantly better RFI and iDFS among patients with HER2DX low-risk versus high-risk tumors. We also evaluated real-world outcomes among 191 patients with metastatic breast cancer. Herein, we demonstrate that T-DXd is associated with relevant real-world activity, with a time-to-next treatment of 9.1 months (range: 7.6 – 10.4) and an overall survival of 22.2 months (range: 17.1 – 25.2). The quantitative proteomic (High Sensitivity-HER2, Reverse Phase Protein Array), transcriptomic (HER2DX) and circulating tumor DNA (DNADX) assessment of HER2 on pre-T-DXd samples enabled a refined prediction of T-DXd efficacy, including in subgroup analyses of HER2-positive and HER2-negative breast cancer. Conclusion: a multi-omic characterization of HER2 expression in pre-treatment tumor samples showed promise in predicting the efficacy of T-DM1 in an adjuvant trial and T-DXd in the real world. Further validation of the biomarkers included in this study is planned within three ongoing phase 2 clinical trials, and may lead in the future to a refined use of anti-HER2 ADCs in clinical practice."],"dc:identifier":["https://hdl.handle.net/2434/1119775","http://dx.doi.org/10.13130/tarantino-paolo_phd2024-12-19","10.13130/tarantino-paolo_phd2024-12-19"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Milano","place:Milano"],"dc:relation":["numberofpages:77"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:subject":["Settore MED/50 - Scienze Tecniche Mediche Applicate"],"dc:title":["ANTIBODY-DRUG CONJUGATES FOR THE TREATMENT OF BREAST CANCER."],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-27T20:18:51Z"}