A large meta-analysis of patients with breast cancer showed that residual cancer burden after neoadjuvant chemotherapy is an accurate long-term predictor of recurrence and survival across all breast cancer subtypes, according to data presented by Yau et al at the 2019 San Antonio Breast Cancer Symposium (Abstract GS5-01).
“In recent years, many single-institution studies have shown that residual cancer burden after neoadjuvant chemotherapy can tell us a great deal about a patient’s prognosis after surgery,” said the study’s senior author W. Fraser Symmans, MD, Professor and Director of Research Operations in the Department of Pathology at The University of Texas MD Anderson Cancer Center. “We undertook this meta-analysis to help determine whether this is true for all subtypes and how generalizable previous findings might be.”
“This meta-analysis of residual cancer burden provides real-world evidence of how patients are responding to neoadjuvant treatments, and calibration of residual cancer burden index to prognostic risk enables us to determine the most appropriate next steps for [patients with breast cancer].”— W. Fraser Symmans, MD
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Residual Cancer Burden
Dr. Symmans explained that residual cancer burden is assessed through several factors, including the size of the primary tumor, the percentage of the tumor that is invasive vs in situ, and the involvement of lymph nodes. A calculator hosted by MD Anderson calculates residual cancer burden index and assigns a classification of pathologic complete response: RCB-I (minimal burden), RCB-II (moderate burden), or RCB-III (extensive burden).
In this study, Dr. Symmans and colleagues from the I-SPY Clinical Trials Consortium compiled and analyzed data from 12 cancer centers or clinical trials, representing approximately 5,100 patients. Using mixed-effect models, they examined associations between the RCB index and both event-free survival and distant recurrence–free survival.
Meta-Analysis Results
The residual cancer burden index was closely associated with both event-free survival and distant recurrence–free survival and was consistent across 12 clinical sites and all four types of breast cancer. In terms of event-free survival, the analysis of residual cancer burden categories showed:
- In patients with hormone receptor (HR)-positive/HER2-negative disease, 11% were classified as having a pathologic complete response, 11% as RCB-I, 53% as RCB-II, and 25% as RCB-III. At the 10-year follow-up, 19% of the pathologic complete response group had had a recurrence or had died, compared with 14% of the RCB-I group, 31% of the RCB-II group, and 48% of the RCB-III group.
- In patients with HR-positive/HER2-positive disease, 38% were classified as having a pathologic complete response, 20% as RCB-I, 33% as RCB-II, and 8% as RCB-III. At the 10-year follow-up, 9% of the pathologic complete response group had had a recurrence or had died, compared with 17% of the RCB-I group, 36% of the RCB-II group, and 55% of the RCB-III group.
- In patients with HR-negative/HER2-positive disease, 69% were classified as having a pathologic complete response, 11% as RCB-I, 16% as RCB-II, and 4% as RCB-III. At the 10-year follow-up, 7% of the pathologic complete response group had had a recurrence or had died, compared with 15% of the RCB-I group, 37% of the RCB-II group, and 40% of the RCB-III group.
- In patients with HR-negative/HER2-negative disease, 43% of patients were classified as having a pathologic complete response, 12% as RCB-I, 33% as RCB-II, and 11% as RCB-III. At the 10-year follow-up, 14% of the pathologic complete response group had had a recurrence or had died, compared with 25% of the RCB-I group, 39% of the RCB-II group, and 75% of the RCB-III group.
Significance of the Findings
“The measurement of residual cancer burden index is strongly prognostic, allowing us to measure risk of recurrence with confidence,” said Dr. Symmans. “This meta-analysis of residual cancer burden provides real-world evidence of how patients are responding to neoadjuvant treatments, and calibration of residual cancer burden index to prognostic risk enables us to determine the most appropriate next steps for [patients with breast cancer].”
Dr. Symmans said that while not all cancer centers routinely collect data on residual cancer burden, this analysis shows that pathologists can implement it with accurate results, adding to its potential as a predictor of recurrence within breast cancer subtypes.
He added that one limitation of the study is that it is based on data from multiple institutions, leading to some variation in clinical methods, the handling of specimens, and possible other factors. Some data on residual cancer burden were collected prospectively and some were collected retrospectively.
“Looking ahead, if we can standardize the reporting of residual cancer burden, that will only improve its usefulness in determining long-term prognosis,” concluded Dr. Symmans said.
Disclosure: This research was funded by the Department of Defense, a National Institutes of Health program grant, the Cancer Prevention Research Institute of Texas, and the Breast Cancer Research Foundation. For full disclosures of the study authors, visit abstractsonline.com.
