Prognostic value of the Residual Cancer Burden index according to breast cancer subtype: validation on a cohort of BC patients treated by neoadjuvant chemotherapy

ABSTRACT Introduction The Residual Cancer Burden (RCB) quantifies residual disease after neoadjuvant chemotherapy (NAC). Its predictive value has not been validated on large cohorts with long-term follow up. The objective of this work is to independently evaluate the prognostic value of the RCB index depending on BC subtypes (Luminal, HER2 -positive and triple negative (TNBCs)). Methods We retrospectively evaluated the RCB index on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between RCB index and relapse-free survival (RFS), overall survival (OS) among the global population, after stratification by BC subtypes. Results 717 patients were included (luminal BC (n = 222, 31%), TNBC (n = 319, 44.5%), HER2 -positive (n = 176, 24.5%)). After a median follow-up of 99.9 months, RCB index was significantly associated with RFS. The RCB-0 patients displayed similar prognosis when compared to the RCB-I group, while patients from the RCB-II and RCB-III classes were at increased risk of relapse (RCB-II versus RCB-0: HR=3.25 CI [2.1-5.1] p <0.001; RCB-III versus RCB-0: HR=5.6 CI [3.5-8.9] p <0.001). The prognostic impact of RCB index was significant for TNBC and HER2 -positive cancers; but not for luminal cancers ( P interaction = 0.07). The prognosis of RCB-III patients was poor (8-years RFS: 52.7%, 95% CI [44.8 – 62.0]) particularly in the TNBC subgroup, where the median RFS was 12.7 months. Conclusion RCB index is a reliable prognostic score. RCB accurately identifies patients at a high risk of recurrence (RCB-III) with TNBC or HER2 -positive BC who must be offered second-line adjuvant therapies.