In an analysis reported in The Lancet Oncology, Yau et al found that increasing residual cancer burden (RCB) after neoadjuvant chemotherapy was associated with poorer event-free survival across breast cancer subtypes.
Study Details
The study included patient-level data on RCB and other clinical and disease characteristics from 5,161 patients from 12 institutes and clinical trials in the United States and Europe. Patients had stage I to III breast cancer and were treated with neoadjuvant chemotherapy followed by surgery between September 1994 and February 2019. RCB score was analyzed as a continuous variable and according to RCB class: RCB-0 = score of 0 (equivalent to pathologic complete response); RCB-1 = scores of ≥ 0 to 1.36; RCB-2 = scores of 1.37 to 3.28; and RCB-3 = scores > 3.28.
The primary outcome measure was the association of RBC score with event-free survival, with analysis according to breast cancer subtype.
Key Findings
Overall:
- 1,774 patients had hormone receptor–negative, HER2-negative disease
- 572 had hormone receptor–negative, HER2-positive disease (488 received HER2-targeted neoadjuvant therapy)
- 858 had hormone receptor–positive, HER2-positive disease (756 received HER2-targeted neoadjuvant therapy)
- 1,957 had hormone receptor–positive, HER2-negative disease.
Among all patients, RCB class was RCB-0 in 1,676 (32.5%), RCB-1 in 662 (12.8%), RCB-2 in 2,017 (39.1%), and RBC-3 in 806 (15.6%).
A total of 1,164 event-free survival events occurred during median follow-up of 56 months (interquartile range = 0–186 months).
RCB score was prognostic for event-free survival in the total population and within each breast cancer subtype, with higher RCB score significantly associated (all P < .0001) with worse event-free survival. On multivariate analysis adjusted for baseline age, grade, T category, and nodal status, hazard ratios associated with each 1-unit increase in RCB score were:
- 1.69 (95% confidence interval [C1] = 1.55–1.85) among all patients
- 1.93 (95% CI = 1.74–2.13) in the hormone receptor–negative, HER2-negative cohort
- 2.09 (95% CI = 1.73–2.53) in the hormone receptor–negative, HER2-positive cohort, including 2.10 (95% CI = 1.68–2.62) among those receiving HER2-targeted neoadjuvant therapy
- 1.66 (95% CI = 1.45–1.90) in the hormone receptor–positive, HER2-positive cohort, including 1.69 (95% CI = 1.45–1.97) among those receiving HER2-targeted neoadjuvant therapy
- 1.52 (95% CI = 1.36–1.69) in the hormone receptor–positive, HER2-negative cohort.
Event-free survival estimates at 3, 5, and 10 years by RCB class were: 94%, 91%, and 88% for RCB-0; 91%, 86%, and 80% for RCB-1; 82%, 74%, and 65% for RCB-2; and 66%, 58%, and 45% for RCB-3. On multivariate analysis, RCB class was significantly prognostic in all subtypes.
The investigators concluded, “RCB score and class were independently prognostic in all subtypes of breast cancer, and generalizable to multiple practice settings. Although variability in hormone receptor subtype definitions and treatment across patients are likely to affect prognostic performance, the association we observed between RCB and a patient’s residual risk suggests that prospective evaluation of RCB could be considered to become part of standard pathology reporting after neoadjuvant therapy.”
Christina Yau, PhD, of the Department of Surgery, University of California, San Francisco, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
