Dados do Trabalho


Update on the ADAMANT-NEO study: Monitoring treatment resistance using ctDNA analysis in non-metastatic Triple-Negative Breast Cancer (TNBC) treated with pre-operative chemotherapy


Loss-of-function germline mutation in BRCA1 increases breast cancer risk, especially the TNBC subtype. BRCA1 impairment may confer benefit from treatment with DNA damage-inducing drugs and PARP1 inhibitors. Patients who respond to neoadjuvant chemotherapy tend to have good outcomes.


Our aim is to characterize the resistance to chemotherapy in patients with germline-characterized TNBC by investigating somatic mutations in ctDNA.


Germline genetic testing using cancer-predisposing gene panels (26-126 genes) for classifying TNBC as Hereditary or Sporadic. Somatic mutation identification in tumor (409 cancer-related gene panel) and screening of ctDNA in plasma samples during treatment.


We enrolled 108 TNBC patients of which 103 were tested for germline variants: 27% (28/103) of cases were Hereditary - BRCA1 (19%), BRCA2 (3%), PALB2 (1%), RAD51C (1%), RAD51D (1%) and TP53 (1%). Tumor mutation burden (TMB) analysis (59) showed that 8.5% had high and 91.5% low TMB, not associated with Hereditary status. Somatic mutations were identified in 95% (53/56) of tumors, with TP53 mutations being the most frequent (84%; 47/56). In ctDNA before treatment, detection of at least one tumor mutation was observed in 37/48 patients (77%) and no association was observed with TMB score. Sporadic tumors were more frequently ctDNA+ at diagnosis than Hereditary tumors (84% vs 50%, respectively, p=0.04), however after treatment no difference was observed. Although ctDNA was not associated to the residual cancer burden (RCB) score, ctDNA detection was associated with clinical progression at baseline (36% ctDNA+ progressed vs 0% of ctDNA-; p=0.02) and after curative-intended treatment (72% ctDNA+ vs 32% in ctDNA-; p=0.01) . ctDNA identification anticipated progression detected by imaging.


Hereditary tumors, markedly due to germline variants in BRCA1, are frequent in TNBC. Tumor-mark identification using gene panel and ctDNA screening in plasma samples provide valuable information regarding clinical progression of patients treated with pre-operative chemotherapy.


triple-negative breast cancer; ctDNA; liquid biopsy

Financiador do resumo

PRONON (2500.055.121\2015-12), FAPESP (2013/23277-8); CNPq (305464/2013-2)


Estudo Clínico - Tumores de Mama


RAFAEL CANFIELD BRIANESE, Giovana Tardin Torrezan, Marina De Brot, Vladmir Claudio Cordeiro de Lima, Solange Moraes Sanches, Maria Nirvana da Cruz Formiga, Fabiana Baroni Alves Makdissi, Dirce Maria Carraro