Residual Cancer Burden Prognostic Across Breast Cancer Phenotypes

Residual cancer burden (RCB) was found to be prognostic for long-term survival following neoadjuvant chemotherapy for three phenotypic subsets of breast cancer in a new single-institution study.

The approval of chemotherapy for high-risk early breast cancer was based on improved pathologic complete response rates following neoadjuvant treatment, but the magnitude of prognostic difference using this metric remains unclear. “Prognostic difference might also depend on the distribution of the extent of residual disease in each treatment arm, if that relates to longer-term prognosis within each phenotypic subset of breast cancer,” wrote study authors led by W. Fraser Symmans, MB, ChB, of the University of Texas MD Anderson Cancer Center in Houston. The results were published in the Journal of Clinical Oncology.

In this study, researchers measured the continuous RCB index wherein a complete pathologic response has an RCB of zero, and residual disease was classified into three categories (RCB-I, RCB-II, and RCB-III). It included five patient cohorts: three received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (FAC; 219 patients, 262 patients, and 342 patients); a validation cohort received the FAC regimen only (132 patients); and a fifth cohort received concurrent trastuzumab (H) with sequential T and fluorouracil, epirubicin, and cyclophosphamide (FEC; 203 patients).

The phenotypic subsets included hormone receptor (HR)-positive/HER2-negative, HER2-positive (including both HR-positive and HR-negative), and triple-negative disease.

The five cohorts had median event-free follow-up of 13.5 years, 9.1 years, 6.8 years, 16.4 years, and 7.1 years, respectively. RCB was significantly prognostic across all cohorts, and regardless of phenotypic subtype. In the combined T/FAC cohorts, the hazard ratio for overall survival based on RCB was 0.73 in HR-positive/HER2-negative patients (95% CI, 0.67–0.78); 0.72 in HER2-positive patients (95% CI, 0.63–0.82); and 0.76 in triple-negative patients (95% CI, 0.70–0.82). Results were similar in the validation cohort and in the H+T/FEC cohort, and were also significant for relapse-free survival and distant relapse–free survival.

RCB class was used to estimate 10-year relapse-free survival rates for each phenotypic subset. For HR-positive/HER2-negative patients in the combined T/FAC cohorts, these rates for the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 83%, 97%, 74%, and 52%, respectively; for triple-negative disease patients, they were 86%, 81%, 55%, and 23%, respectively; and for the H+T/FEC patients, the rates were 95%, 77%, 47%, and 21%.

“Evaluation of RCB index and class could be useful because it appears to provide relevant, long-term prognostic data, which add meaningful information to pretreatment clinical and pathologic information,” the authors concluded.

In an accompanying editorial, Sibylle Loibl, MD, and Carsten Denkert, MD, both of the German Breast Group in Neu-Isenburg, Germany, wrote that this study does confirm the prognostic impact of RCB, but that the use of this measure remains unclear. “The granularity of the prognostic information needed after neoadjuvant chemotherapy clearly depends on the clinical consequences,” they wrote. “Today, the impact that such information has on future clinical management might be limited….Certainly, the use of RCB might be promising when a more refined assessment of response is required.”