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| Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Dec 3. pii: 1078-0432.CCR-21-3231. doi: 10.1158/1078-0432.CCR-21-3231 |
| Persistence of ctDNA in breast cancer patients during neoadjuvant treatment is a significant predictor of poor tumour response. |
| Zhou Q1, Gampenrieder SP2, Frantal S3, Rinnerthaler G4, Singer CF5, Egle D6, Pfeiler G7, Bartsch R8, Wette V9, Pichler A10, Petru E11, Dubsky PC12, Bago-Horvath Z13, Fesl C14, Rudas M15, Ståhlberg A16, Graf R17, Weber S18, Dandachi N19, Filipits M20, Gnant M21, Balic M22, Heitzer E23 |
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Abstract PURPOSE: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally-invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. EXPERIMENTAL DESIGN: We profiled 93 genes in tissue from 193 early breast cancer patients. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR), residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. RESULTS: At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR 0.062, 95% CI 0.01-0.48, =0.0077).Out of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were non-responders (RCB II, n=8; RCB III, n=22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, while 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. CONCLUSION: Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III. |
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Publikations ID: 34862246 Quelle: öffnen |
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