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

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.

Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response

“…An important novelty of our study is the analysis of RCB as a further endpoint of the ABCSG-34 trial in addition to pCR. Although pCR is the most commonly used pathologic staging system to risk-stratify patients following completion of neoadjuvant chemotherapy for breast cancer ( 48 ), the value of RCB as an indicator of long-term survival for patients after NST has been recognized ( 24, 31 ) and validated ( 49, 50 ). A stratification into good response classes (RCB 0/I) and bad response classes (RCBII/III) provides prognostic information for all molecular subtypes and neoadjuvant treatment regimens.…”

Clearance of ctDNA in triple-negative and HER2-positive breast cancer patients during neoadjuvant treatment is correlated with pathologic complete response

“…A second limitation of this study is that the post-surgery follow-up time was restricted to 12 months, so it is not possible to rule out any other potential recurrence in the future, as the recurrence window of HER2+ and TN BC is estimated to be 5 years, or even more in the case of luminal tumors. 36 Given these limitations (only two patients had recurred at the writing of this manuscript), ctDNA levels could not be assessed as a prognostic factor for recurrence. In addition, we were unable to perform post-surgery surveillance blood testing of all patients and at all of the scheduled time points during the follow-up.…”

Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

“…These tumors are positive for CK 5/6, CK 14, and vimentin [ 83 ]. EBVrBCa is more common in younger females, is present with a larger tumor size, and has a higher histological grade, thereby it is associated with lower overall survival rates [ 79 , 84 ].…”