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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.
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.
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.
Shares Natera, Tumour-informed versus tumour-naive ctDNA assays, Signatera, Circulating tumour DNA (ctDNA).
Shares Laura J. Esserman, I-SPY 2, UCSF Helen Diller Family Comprehensive Cancer Center, Breast cancer (all types).
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Pathologic complete response (pCR), Circulating tumour DNA (ctDNA), Early triple-negative breast cancer.
Shares Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, Circulating tumour DNA (ctDNA).
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing, Early triple-negative breast cancer.
Shares Laura J. Esserman, UCSF Helen Diller Family Comprehensive Cancer Center, Pathologic complete response (pCR), Breast cancer (all types).
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares Tumour-informed versus tumour-naive ctDNA assays, ctDNA MRD positivity (molecular residual disease after curative treatment), Signatera, Circulating tumour DNA (ctDNA).