Patterns of Recurrence after Neoadjuvant Therapy in Early Breast Cancer, according to the Residual Cancer Burden Index and Reductions in Neoadjuvant Treatment Intensity

SIMPLE SUMMARY: The residual cancer burden (RCB) score provides prognostic information on the survival of breast cancer patients who underwent neoadjuvant systemic therapy, with the greatest impact of higher scores on worse recurrence-free survival (RFS) and overall survival (OS) in triple-negative and HER2 positive patients. The impact of chemotherapy dose reduction on RCB is currently unknown, and should therefore be critically evaluated by clinicians. Our study confirms the prognostic relevance of the RCB score and suggests a potential association of the RCB with dose reduction having adverse impact on the RCB, thereby potentially impacting the prognosis of patients, as shown here in a large breast cancer cohort at the Medical University of Graz. ABSTRACT: Background: The prognostic performance of the residual cancer burden (RCB) score is a promising tool for breast cancer patients undergoing neoadjuvant therapy. We independently evaluated the prognostic value of RCB scores in an extended validation cohort. Additionally, we analyzed the association between chemotherapy dose reduction and RCB scores. Methods: In this extended validation study, 367 breast cancer patients with available RCB scores were followed up for recurrence-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). We also computed standardized cumulative doses of anthracyclines and taxanes (A/Ts) to investigate a potential interaction between neoadjuvant chemotherapy dose reduction and RCB scores. Results: Higher RCB scores were consistently associated with adverse clinical outcomes across different molecular subtypes (HR for RFS = 1.60, 95% CI 1.33–1.93, p < 0.0001; HR for DDFS = 1.70, 95% CI 1.39–2.05, p < 0.0001; HR for OS = 1.67, 95% CI 1.34–2.08, p < 0.0001). The adverse impact prevailed throughout 5 years of follow-up, with a peak for relapse risk between 1–2 years after surgery. Clinical outcomes of patients with RCB class 1 did not differ substantially at 5 years compared to RCB class 0. A total of 180 patients (49.1%) underwent dose reduction of neoadjuvant A/T chemotherapy. We observed a statistically significant interaction between dose reduction and higher RCB scores (interaction p-value = 0.042). Conclusion: Our results confirm RCB score as a prognostic marker for RFS, DDFS, and OS independent of the molecular subtype. Importantly, we show that lower doses of cumulative neoadjuvant A/T were associated with higher RCB scores in patients who required a dose reduction.