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The UK trial that watched 161 women with early triple-negative breast cancer by three-monthly blood tests for tumour DNA: 27 percent tested positive within a year, but by then nearly three quarters already had visible metastases, and none of the five who started pembrolizumab cleared the DNA. The lesson was to test earlier and more sensitively.
c-TRAK TN (Turner, Swift, Jenkins, Kilburn and colleagues), a multicentre phase 2 trial with prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy, or stage II to III disease after adjuvant chemotherapy, for three-monthly sampling to 12 months (18 if samples were missed during the pandemic). ctDNA-positive patients were randomised 2:1 to intervention (staging scans, then pembrolizumab if free of recurrence) or observation until a September 2020 amendment allocated all to intervention. Of 208 registered, 185 had tumour sequenced, 171 (92.4 percent) had trackable mutations and 161 entered surveillance. ctDNA was detected by 12 months in 27.3 percent (44 of 161, 95 percent confidence interval 20.6 to 34.9); seven patients relapsed without prior detection. Of 32 allocated to intervention, 72 percent (23) had metastases on staging at ctDNA detection and four declined pembrolizumab; none of the five who started it achieved sustained ctDNA clearance.
The first prospective test of acting on ctDNA in triple-negative disease, and a negative one: with a quarterly, single-mutation assay the window between detectable DNA and visible metastasis was too short to intervene. Later designs use tumour-informed assays, earlier sampling and drugs with more single-agent activity.
Shares ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative, Residual cancer burden (RCB), Dormant cells and minimal residual disease, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem and the tag tnbc-evidence.
Shares ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative, Residual cancer burden (RCB), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative, Residual cancer burden (RCB), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC), Immune checkpoint inhibitors and the tag tnbc-evidence.
Shares Annals of Oncology, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Residual cancer burden (RCB), Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.
Shares Trial design, endpoints and cost, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem, Pembrolizumab, Triple-negative breast cancer (TNBC) and the tag tnbc-evidence.