144P Factors affecting long term outcomes in patients with pathologic complete response after neoadjuvant chemotherapy for early breast cancer: A population-based study

Pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT) for early breast cancer is strongly prognostic. However, pCR is not a surrogate marker for long-term outcome at a trial level. Here, we aimed to investigate which other factors affect patient outcomes following pCR. Patients receiving NACT for non-metastatic breast cancer, diagnosed between 2007 and 2020, in the healthcare region of Stockholm-Gotland were identified using the National Quality Register for Breast Cancer. Clinicopathological data, along with treatment and patient outcome were extracted from medical charts as well as from multiple registries. Factors affecting distant relapse-free survival (DRFS) were analyzed using a multivariable, non-proportional hazards model. Hazards over time were plotted using restricted cubic spline-based estimates. Median follow-up was 6.5 years. Of 2487 patients, 661 (26.6%) attained pCR. Rates of pCR were 45.4% in HER2+, 33.9% in triple-negative and 8.6% in luminal tumors. Patients reaching pCR had improved adjusted DRFS using inverse probability weighting. Both patients with residual disease and, to a lesser extent, with pCR had a peak in distant recurrence risk 1 year post-surgery, followed by a sharp decline in risk, which however remained elevated for non-pCR patients for more than a decade postoperatively. Among patients with pCR, age (HRadj=1.04, 95% CI 1.01-1.06), T3/T4 stage (HRadj=2.02, 95% CI 1.05-3.87) and HER2 positivity (HRadj=0.34, 95% CI 0.17-0.68) were associated with DRFS, while node positivity predicted distant recurrence during the first year post surgery (HRadj=2.84, 95% CI 1.16 – 6.94) and ER positivity predicted distant recurrence at 5-10 years (HRadj=4.30, 95% CI 1.06 – 17.49). Local relapse as first site of recurrence was more common in non-pCR patients (4.8% vs 1.8%, p=0.00047). CNS relapse was not affected by pCR status (5.1% vs 3.9%, p=0.13). In this population-based study, we show that patients with pCR following NACT are a heterogeneous group regarding long-term outcomes. Baseline tumor characteristics should be considered when investigating post-neoadjuvant therapy approaches.