title: Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.
abstract: 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.
  
  
  
  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).
  
  
  
  Forty-six patients with nonmetastatic TNBC were enrolled.TP53mutations 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.
  
  
  
  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.
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.|Department of Medical Oncology, San Gerardo Hospital, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Riva
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France; francois-clement.bidard@curie.fr.|Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
authors.forename: Francois-Clement
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: INSERM U830, Institut Curie, PSL Research University, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Houy
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Saliou
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.
authors.forename: Jordan
authors.initials: J
authors.lastname: Madic
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.|INSERM CIC-BT 1428, Institut Curie, PSL Research University, Paris, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Rampanou
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hego
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.|INSERM CIC-BT 1428, Institut Curie, PSL Research University, Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Milder
authors.affiliation: Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.affiliation: Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Sablin
authors.affiliation: Department of Biopathology, Institut Curie, PSL Research University, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.affiliation: INSERM CIC-BT 1428, Institut Curie, PSL Research University, Paris, France.|Department of Biopathology, Institut Curie, PSL Research University, Paris, France.|Department of Tumor Biology, Institut Curie, PSL Research University, Paris, France.|INSERM U932, Institut Curie, PSL Research University, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantz
authors.affiliation: INSERM U830, Institut Curie, PSL Research University, Paris, France.
authors.forename: Marc-Henri
authors.initials: MH
authors.lastname: Stern
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Proudhon
authors.affiliation: Laboratory of Circulating Tumor Biomarkers, Institut Curie, PSL Research University, SiRIC, Paris, France.|Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
mesh_terms: D004273:DNA, Neoplasm / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016133:Polymerase Chain Reaction; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000628:therapy*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53