{"entity":{"id":"paper-slamon-trastuzumab-nejm-2001","kind":"paper","name":"Slamon 2001: adding trastuzumab to chemotherapy for HER2-positive metastatic breast cancer","aka":[],"tldr":"The trial that made trastuzumab standard: adding the HER2 antibody to chemotherapy slowed progression and prolonged life in women whose breast cancers overexpressed HER2, at the cost of heart weakening when it was paired with anthracyclines.","summary":"This phase 3 trial randomised 469 women with previously untreated HER2-overexpressing metastatic breast cancer to chemotherapy (an anthracycline plus cyclophosphamide, or paclitaxel for those who had received adjuvant anthracycline) with or without trastuzumab. Adding trastuzumab lengthened the time to progression and raised the response rate, and it improved overall survival despite two thirds of the chemotherapy-alone group receiving trastuzumab after progression. Cardiac dysfunction was markedly more frequent when trastuzumab was combined with the anthracycline, which is why the two are not given together today.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJM200103153441101"}],"tags":[],"related":["paper-slamon-her2-amplification-science-1987"],"cancers":["breast-her2-positive"],"sections":[],"technologies":[],"targets":["her2"],"drugs":["trastuzumab","paclitaxel"],"companies":["roche-genentech"],"institutions":[],"pathways":[],"terms":["os","orr"],"trials":[],"people":["dennis-slamon"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2001,"doi":"10.1056/NEJM200103153441101","authors":"Slamon DJ, Leyland-Jones B, Shak S, et al.","paperType":"rct","findings":["469 women with HER2-overexpressing metastatic breast cancer; chemotherapy with or without trastuzumab.","Time to progression 7.4 vs 4.6 months; objective response 50% vs 32%.","Median overall survival 25.1 vs 20.3 months, hazard ratio for death 0.80.","Cardiac dysfunction in 27% of patients given anthracycline plus trastuzumab versus 8% with anthracycline alone, and 13% with paclitaxel plus trastuzumab."],"whatItMeans":"This was the first proof that a monoclonal antibody against a growth receptor could extend life in a common solid tumour, and it created HER2-positive breast cancer as a disease treated differently from the rest. Its cardiac finding shaped every later HER2 regimen, which pair trastuzumab with taxanes rather than anthracyclines.","caveats":["Crossover to trastuzumab after progression diluted the survival difference.","HER2 positivity was defined by immunohistochemistry 2+ or 3+, broader than the 3+ or amplified definition used now.","Open-label design."],"changedPractice":true,"participants":469},"route":"/key-papers/paper-slamon-trastuzumab-nejm-2001/","neighbours":{"paper":[{"id":"paper-slamon-her2-amplification-science-1987","kind":"paper","name":"Slamon 1987: HER2 gene amplification marks an aggressive form of breast cancer","route":"/key-papers/paper-slamon-her2-amplification-science-1987/"},{"id":"paper-slamon-her2-breast-ovarian-science-1989","kind":"paper","name":"Slamon 1989: HER2/neu in human breast and ovarian cancer","route":"/key-papers/paper-slamon-her2-breast-ovarian-science-1989/"},{"id":"paper-toga-trastuzumab-gastric-lancet-2010","kind":"paper","name":"ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer","route":"/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/"}],"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"drug":[{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"}],"company":[{"id":"roche-genentech","kind":"company","name":"Roche / Genentech","route":"/companies/roche-genentech/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"person":[{"id":"dennis-slamon","kind":"person","name":"Dennis J. Slamon","route":"/people/dennis-slamon/"}]}}