Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study

2021 ◽  
Author(s):  
Haeyoung Kim ◽  
Yeon Jeong Kim ◽  
Donghyun Park ◽  
Woong-Yang Park ◽  
Doo Ho Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Observational Study ◽  
Triple Negative Breast Cancer ◽  
Prospective Observational Study ◽  
Triple Negative ◽  
Postoperative Radiotherapy ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

2017 ◽  
Vol 63 (3) ◽  
pp. 691-699 ◽  
Author(s):  
Francesca Riva ◽  
Francois-Clement Bidard ◽  
Alexandre Houy ◽  
Adrien Saliou ◽  
Jordan Madic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Minimal Residual Disease ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Circulating Tumor Dna ◽  
Tp53 Mutations ◽  
Tumor Dna ◽  
Minimal Residual

Abstract BACKGROUND In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. METHODS Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 (TP53) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). RESULTS Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS (r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index (P = 0.003), tumor grade (P = 0.003), and stage (P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free (P < 0.001) and overall (P = 0.006) survival. CONCLUSIONS Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival.

scholarly journals Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Luca Cavallone ◽  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Mohammed Aldamry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Triple Negative ◽  
Residual Tumor ◽  
Complete Response ◽  
Circulating Tumor Dna ◽  
Droplet Pcr ◽  
Tumor Dna

Abstract Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline. Mutant allele frequency at baseline was associated with clinical characteristics. Levels drastically fell after one cycle of NAC, especially in patients whose tumors would go on to have a pathological complete response (pCR), but then rose significantly before surgery in patients with significant residual tumor at surgery (p = 0.0001). The detection of ctDNA early during treatment and also late at the end of NAC before surgery was strongly predictive of residual tumor at surgery, but its absence was less predictive of pCR, especially when only TP53 variants are considered. ctDNA detection at the end of neoadjuvant chemotherapy indicated significantly worse relapse-free survival (HR = 0.29 (95% CI 0.08–0.98), p = 0.046), and overall survival (HR = 0.27 95% CI 0.075–0.96), p = 0.043). Hence, individualized multi-variant ctDNA testing during and after NAC prior to surgery has prognostic and predictive value in early TNBC patients.

Monitoring of circulating tumor DNA in metastatic triple-negative breast cancer patients undergoing chemotherapy.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e22056-e22056
Author(s):  
Jordan Madic ◽  
Anna Kiialainen ◽  
Francois-Clement Bidard ◽  
Fabian Birzele ◽  
Guillemette Ramey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Circulating Tumor Dna ◽  
Breast Cancer Patients ◽  
Tumor Dna
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