RESIDUAL CANCER BUREN INDEX AS PROGNOSTIC FACTOR AFTER NEOADJUVANT CHEMOTHERAPY OF BREAST CANCER

In a study reported in the Journal of Clinical Oncology, Symmans et al found that residual cancer burden (RCB) after neoadjuvant chemotherapy was significantly prognostic for long-term outcome across breast cancer subtypes.

Study Details

The study included 5 patient cohorts from The University of Texas MD Anderson Cancer Center: 3 received paclitaxel (T) followed by fluorouracil (5-FU), doxorubicin, and cyclophosphamide (T/FAC), including a development cohort (T/FAC-1, n = 219), a validation cohort (T/FAC-2, n = 262), and an independent validation cohort (T/FAC-3, n =342); another validation cohort received FAC only (n =132); a fifth cohort received concurrent trastuzumab (Herceptin; H) with sequential paclitaxel and 5-FU, epirubicin, and cyclophosphamide (H+T/FEC, n = 203).

A pathologic review assessed residual cancer burden index, with pathologic complete response indicated by RCB = 0 and minimal, moderate, and extensive residual disease indicated by RCB-I, RCB-II, and RCB-III, respectively. Breast cancer subtypes were hormone receptor–positive/HER2-negative, HER2-positive (hormone receptor–negative or –positive), and triple-negative.

Prognostic Ability of Residual Cancer Burden Index

Median follow-up for survivors in the T/FAC-1, T/FAC-2, T/FAC-3, FAC, and H+T/FEC cohorts were 13.5, 9.1, 6.4 (8.2 for combined T/FAC cohorts), 16.4, and 7.1 years, respectively. The continuous residual cancer burden index was prognostic for risk of relapse or death with hazard ratios (HRs) per unit of residual cancer burden index being significant in all 5 cohorts (HRs ranged from 1.78–2.25 for relapse-free survival, 1.79–2.22 for distant relapse-free survival, and 1.74–2.39 for overall survival) and in all 3 phenotype subgroups in the combined T/FAC cohorts independent of other clinical and pathologic variables.

Hazard ratios for relapse-free, distant relapse–free, and overall survival were 1.89, 1.95, and 1.92 for triple-negative disease; 1.95, 1.99, and 1.98 for hormone receptor–positive/HER2-negative disease; and 1.91, 1.93, and 1.81 for HER2-positive disease in the combined T/FAC cohorts.

The residual cancer burden classes stratified prognostic risk overall, within each phenotype subgroup, and within yp-stage categories. For example, estimated 10-year relapse-free survival rates in the residual cancer burden = 0, -I, -II, and -III classes were 86%, 81%, 55%, and 23% for triple-negative disease and 83%, 97%, 74%, and 52% for hormone receptor–positive/HER2-negative disease in the combined T/FAC cohorts and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. Residual cancer burden classes were prognostic for relapse-free survival in yp-stage II (n = 418; P = .002 for RCB-I vs II vs III) and yp-stage III (n = 259; P = .007 for RCB-II vs III) but not significantly in yp-stage I (n = 218; P = .403 for RCB-I vs II).

The investigators concluded: “[Residual cancer burden] was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.”

The study was supported by the Department of Defense Congressionally Directed Funds for Breast Cancer Research, the Breast Cancer Research Foundation, Susan G. Komen for the Cure, and the Nellie B. Connally Breast Center at MD Anderson Cancer Center.