Validation of Residual Cancer Burden as Prognostic Factor for Breast Cancer Patients After Neoadjuvant Therapy

Abstract

Background. Assessing the residual cancer burden (RCB) predictive performance, the potential subgroup effects, and time-dependent impact on breast cancer patients who underwent neoadjuvant therapy in a developer's independent cohort is essential for its usage in clinical routine. Methods. Between 2011 and 2016, the RCB scores of 184 female breast cancer patients were prospectively collected, and subsequent clinicopathological and follow-up data were obtained retrospectively. Recurrence-free survival (RFS), overall survival (OS), as well as subgroup analysis, and time-dependent variables were calculated with multivariate, complex, or linear statistical models. Results. A total of 184 patients (HER2 33%, TNBC 27%), with a mean follow-up time of 4 years, treated with neoadjuvant systemic therapy (92% anthracycline-taxane based) were analyzed revealing 43 events (38 recurrences, 28 deaths). High RCB scores were associated with recurrence (median index: 2.34 vs. 1.39 points, rank-sum p \ 0.0001), decreased RFS (hazard ratio [HR] = 1.80, 95% confidence interval [CI] 1.44-2.24, p \ 0.0001) and reduced OS (HR 1.96, 95% CI 1.49-2.59, p \ 0.0001). The RCB score showed proportionality of hazards (interaction HR with linear follow-up time = 1.00, p = 0.896) and good discriminating power (Harrell's c index 0.7). Conclusions. Our results confirm the RCB score as externally valid prognostic marker and being independent of molecular subtype for RFS and OS in a clinical setting.

Time to surgery following neoadjuvant chemotherapy for breast cancer impacts residual cancer burden, recurrence, and survival

“…Our data suggest that regrowth of potentially resistant tumor cell populations after NAC may increase RCB score after 6 weeks, and may mediate the observed association of TTS with recurrence and survival. It should be noted that Müller and Symmans have shown that the prognostic impact of changes in the RCB score within RCB classes is low 8,9 . While the increase in RCB score associated with TTS >6 weeks may not be relevant to patients destined to have RCB scores on the low end of Class‐I or Class‐II, patients on the higher end of RCB class cutoffs may experience “upstaging” to a higher RCB class with longer TTS intervals, particularly beyond 6 weeks.…”

Unmet Clinical Need: Developing Prognostic Biomarkers and Precision Medicine to Forecast Early Tumor Relapse, Detect Chemo-Resistance and Improve Overall Survival in High-Risk Breast Cancer

“…However, RCB has been determined to be prognostic for 10-year relapse-free survival rates for multiple patient cohorts treated with different NACTs including fluorouracil, doxorubicin, and cyclophosphamide (FAC), paclitaxel with FAC, and trastuzumab with sequential paclitaxel and fluorouracil, epirubicin and cyclophosphamide. RCB classification was prognostic for TNBC, HR + /HER2and HER2 + phenotypes independent of other prognostic factors [62,63]. While patients with an RCB score 3 have an extremely high risk of tumor recurrence, the risk is lower but still substantial for patients with an RCB score 1-2.…”

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

“…In a previous study, we validated RCB as an independent prognostic factor for breast cancer patients' survival after neoadjuvant therapy in a single institutional study [13]. The primary objective of the present analyses was to validate these findings in a larger cohort of breast cancer patients, as measured by five-year recurrence-free survival.…”

“…We extended our previously published validation study on the prognostic value of RCB score [13] by analyzing 367 breast cancer patients who underwent neoadjuvant treatment at the Division of Oncology, Department of Internal Medicine, Medical University of Graz between 2011 and 2020. The ethics committee of the Medical University of Graz (ethical approval number 31-212 ex 18/19) approved the study.…”

“…Histological diagnosis was performed on pre-therapeutic core needle biopsies and included assessment of ER, PR, HER2, and Ki67 labeling index according to the WHO guidelines, as previously described [13]. Post-therapeutic ypTNM classification and RCB were assessed on the surgical specimens.…”