255P - Patient-specific circulating tumor DNA detection during neoadjuvant chemotherapy in triple negative breast cancer

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Breast Cancer, Metastatic
Presenter Jean-Yves Pierga
Citation Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365
Authors J. Pierga1, F. Riva2, A. Houy3, A. Saliou4, J. Madic4, A. Rampanou4, C. Hego4, M. Milder5, P. Cottu1, M. Sablin1, A. Vincent-Salomon6, O. Lantz5, M. Stern3, C. Proudhon4, F. Bidard1
  • 1Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 2Circulating Biomarkers Lab Siric, Institut Curie, Paris/FR
  • 3Inserm U830, Institut Curie, Paris/FR
  • 4Circulating Biomarkers Lab, Institut Curie, Paris/FR
  • 5Inserm U932, Institut Curie, Paris/FR
  • 6Biopathology, Institut Curie, Paris/FR

Abstract

Background

Proof-of-concept studies also suggested the use of ctDNA levels as a dynamic biomarker reflecting the tumor response to therapy in metastatic breast cancer patients. We previously reported that TP53 mutations can be detected in the plasma of most metastatic Triple Negative Breast Cancer (TNBC) patients. Yet, few data about ctDNA levels and changes during neoadjuvant chemotherapy (NCT) are available for localized breast cancer. We investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to NCT and detect minimal residual disease after surgery non-metastatic TNBC patients.

Methods

10 ml of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized ddPCR assays were used to track TP53 mutations previously characterized in tumor tissue by massively parallel sequencing (MPS).

Results

Forty-six patients with non-metastatic 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 one. 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 one cycle of NCT was correlated with shorter disease-free (p 

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. If confirmed by further prospective studies, ctDNA may become a clinically valuable prognostic tool to manage TNBC patients treated by NCT.

Clinical trial identification

NCT02220556

Legal entity responsible for the study

Institut Curie

Funding

ITMO Santé Publique and SIRIC Institut Curie

Disclosure

All authors have declared no conflicts of interest.