Previous epidemiologic studies investigating central venous catheter (CVC)-related venous thromboembolism (CRT) were conducted in heterogenous cancer populations and data in breast cancer (BC) remain limited. To investigate the Doppler ultrasound (DUS)-CRT incidence, risk factors and outcomes in BC, we designed a prospective, multicenter cohort of nonmetastatic invasive BC patients undergoing insertion of a CVC for chemotherapy. All patients underwent double-blind DUS before, 7, 30, and 90 days after CVC insertion and a 6 months clinical follow-up. Symptomatic DUS-CRT were treated by anticoagulants. D-Dimers, thrombin generation, and platelet-derived microparticles were measured before and 2 days after CVC placement. In DUS-CRT patients, a nested case–control study analyzed the role of thrombophilia. Among 524 patients, the DUS-CRT (14 symptomatic, 46 asymptomatic) cumulative probability was 9.6% at 3 months and 11.5% at 6 months (overall incidence rate: 2.18/100 patient-months). Ten/14 symptomatic DUS-CRT were detected on double-blind DUS before the clinical symptoms, and 3/14 had a simultaneous pulmonary embolism. No clinical thrombotic event subsequently occurred in untreated asymptomatic DUS-CRT. Age >50 years (OR, 1.80; 95% CI, 1.01–3.22), BMI >30 kg/m² (OR, 2.64; 95% CI, 1.46–4.76) and comorbidities (OR, 2.05; 95% CI, 1.18–3.56) were associated with DUS-CRT. No biomarkers was found to predict DUS-CRT. In multivariate analysis, BMI >30 kg/m² (OR, 2.66; 95%CI, 1.46–4.84) and lobular carcinoma histology (OR, 2.56; 95%CI, 1.32–4.96) remained the only significant DUS-CRT risk factors. Thrombophilia did not account for DUS-CRT. Only clinical parameters identified high risk DUS-CRT patients who may be considered for thromboprophylaxis.