Circulating tumor DNA dynamics using patient-customized assays are associated with outcome in neoadjuvantly treated breast cancer
| Autor: | Katie Johnson-Camacho, Taylor Kelley, Joe W. Gray, Daira Melendez, Paul T. Spellman, Christopher L. Corless, Shaadi Tabatabaei, Christopher Boniface, Tim Butler |
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| Rok vydání: | 2018 |
| Předmět: |
Oncology
Adult medicine.medical_specialty medicine.medical_treatment Locally advanced Breast Neoplasms Circulating Tumor DNA 03 medical and health sciences 0302 clinical medicine Breast cancer neoplasm of the breast Internal medicine medicine Humans Good outcome Precision Medicine Pathological Triple negative Complete response Mastectomy 030304 developmental biology Aged 0303 health sciences Chemotherapy business.industry General Medicine Sequence Analysis DNA Middle Aged medicine.disease Neoadjuvant Therapy 3. Good health Treatment Outcome Circulating tumor DNA 030220 oncology & carcinogenesis Female business Research Article |
| Zdroj: | Cold Spring Harbor Molecular Case Studies |
| ISSN: | 2373-2873 |
| Popis: | Pathological complete response (pCR) is an accurate predictor of good outcome following neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. The presence of circulating-tumor DNA (ctDNA) has recently been reported to be strongly predictive of poor outcome in similar patient groups. We monitored ctDNA levels from 10 women undergoing NAC for locally advanced breast cancer using a patient-specific, hybrid-capture sequencing technique sensitive to the level of one altered allele in 10,000. Plasma was collected prior to the start of NAC, prior to each infusion of NAC, and during follow-up for between 350 and 1150 d after the start of NAC. Prior to the start of NAC, ctDNA was detectable in 3/3 triple negative, 3/3 HER2+, and 2/4 HER2−, ER+ breast cancer patients. Total cell-free DNA levels were considerably higher when patients were on NAC than at other times. ctDNA dynamics during NAC showed that patients with pCR experienced rapid declines in ctDNA levels, whereas patients without pCR typically showed evidence of residual ctDNA after initiation of treatment. Intriguingly, two of three patients that showed marked increases in ctDNA while on NAC experienced rapid recurrences (+ disease and showed residual ctDNA after surgery, which became undetectable after local radiation. Taken together, these results demonstrate the ability of our approach to sensitively serially monitor ctDNA during NAC, and identifies a need to further investigate the possibility of stratifying patients who need additional treatment or identify therapies that are ineffective. |
| Databáze: | OpenAIRE |
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