{"entity":{"id":"paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021","kind":"paper","name":"Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival","aka":[],"tldr":"Tracking sixteen patient-specific mutations in blood during chemotherapy before surgery showed that every woman whose tumour vanished had cleared her ctDNA, and that women whose tumour did not vanish but whose ctDNA had cleared did just as well as those it did.","summary":"Cell-free DNA from 291 plasma samples of 84 high-risk early breast cancer patients (I-SPY 2, standard neoadjuvant chemotherapy with or without the AKT inhibitor MK-2206) was tested with a personalised 16-mutation assay at pretreatment, three weeks, between regimens and before surgery. ctDNA positivity fell from 73% to 35%, 14% and 9%. Patients still positive at three weeks were more likely to have residual disease (83% versus 52% non-pCR; OR 4.33). All 17 pCR patients were ctDNA-negative after chemotherapy; among 43 non-pCR patients the 14% who were ctDNA-positive had a metastatic recurrence HR of 10.4, whereas ctDNA-negative non-pCR patients did as well as pCR patients (HR 1.4). Median follow-up 4.8 years.","asOf":"2026-09-24","links":[{"label":"Magbanua et al., Ann Oncol 2021: ctDNA during neoadjuvant therapy in 84 I-SPY 2 patients","url":"https://doi.org/10.1016/j.annonc.2020.11.007"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/33232761/"}],"tags":[],"related":["ctdna-mrd-positive"],"cancers":["tnbc","tnbc-early","breast-cancer"],"sections":[],"technologies":["mrd-testing"],"targets":[],"drugs":["signatera"],"companies":["natera"],"institutions":["ucsf"],"pathways":[],"terms":["ctdna","pcr","tumour-informed-assay"],"trials":["i-spy-2"],"people":["laura-esserman"],"bottlenecks":[],"keyPapers":[],"journals":["annals-of-oncology"],"dependsOn":[],"notes":[],"journal":"Annals of Oncology","year":2021,"doi":"10.1016/j.annonc.2020.11.007","pmid":"33232761","authors":"Magbanua MJM, Swigart LB, Wu HT, et al.","paperType":"translational","findings":["ctDNA positive 73% at baseline, 9% before surgery.","All pCR patients ctDNA-negative; ctDNA-positive non-pCR: recurrence HR 10.4; ctDNA-negative non-pCR: HR 1.4."],"whatItMeans":"ctDNA clearance may refine pCR as a surrogate: a patient with residual disease but no ctDNA may not need escalation, the hypothesis behind ctDNA-guided post-neoadjuvant trials.","caveats":["84 patients mixing HR-positive/HER2-negative and TNBC.","Tumour-informed assay requires exome sequencing of the pretreatment tumour."],"changedPractice":false,"participants":84},"route":"/key-papers/paper-magbanua-ispy2-ctdna-neoadjuvant-ann-oncol-2021/","neighbours":{"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"tnbc-early","kind":"cancer","name":"Early triple-negative breast cancer","route":"/cancers/tnbc-early/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"company":[{"id":"natera","kind":"company","name":"Natera","route":"/companies/natera/"}],"institution":[{"id":"ucsf","kind":"institution","name":"UCSF Helen Diller Family Comprehensive Cancer Center","route":"/institutions/ucsf/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"},{"id":"tumour-informed-assay","kind":"term","name":"Tumour-informed versus tumour-naive ctDNA assays","route":"/terms/tumour-informed-assay/"}],"trial":[{"id":"i-spy-2","kind":"trial","name":"I-SPY 2","route":"/trials/i-spy-2/"}],"person":[{"id":"laura-esserman","kind":"person","name":"Laura J. Esserman","route":"/people/laura-esserman/"}],"journal":[{"id":"annals-of-oncology","kind":"journal","name":"Annals of Oncology","route":"/journals/annals-of-oncology/"}]}}