Results from a pooled analysis of more than 5,100 breast cancer patients from six countries found residual cancer burden (RCB) continuous index and classification were independently and strongly prognostic for all breast cancer phenotypes. The results of this multi-institution collaboration were presented by W. Fraser Symmans, M.D., professor of Pathology at the University of Texas MD Anderson Cancer Center during the 2019 San Antonio Breast Cancer Symposium last week.
Recent studies support the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy for breast cancer. For example, results reported from the I-SPY 1 Trial in 2017 (Campbell et al. Breast Cancer Res Treat), found that Pathologic complete response (pCR) identified patients at lowest risk of recurrence, while RCB and the American Joint Committee on Cancer post-neoadjuvant staging system identified patients at highest risk. That trial analyzed data from just 162 patients. So there has been great interest in further establishing the optimal way to calculate a patient’s risk of recurrence.
“This meta-analysis indicates that continuous RCB index is an accurate and reliable tool to assess patient prognosis,” said Symmans, in his presentation of this latest study. “Furthermore, we found that these results were consistently generalizable and could help determine the most appropriate treatment plans for patients with all breast cancer subtypes.”
MD Anderson has hosted a freely available website to calculate RCB since 2007. This is widely used as a resource with educational materials and calculator for RCB index and category. RCB is determined by factors including the dimensions of the primary tumor bed area; the percentage of cancer that is invasive versus in situ; the number of involved lymph nodes and size of the largest metastasis. RCB index categories are: RCB-I (minimal burden), RCB-II (moderate burden) or RCB-III (extensive burden).
In their study, Symmans worked with a team of researchers from the I-SPY Clinical Trials Consortium to analyze data from 12 institutes or clinical trials representing more than 5,100 breast cancer patients. I-SPY comprises a series of trials and its centerpiece is a novel platform trial for neoadjuvant treatment of locally advanced breast cancer.
Symmans and colleagues evaluated associations between the continuous RCB index and both event-free survival (EFS) and distant recurrence-free survival (DRFS), adjusting for differences between studies. They also evaluated the association between RCB index and prognosis within each HR/HER2 subtype. Kaplan Meier estimates of EFS and DRFS at five and 10 years were calculated for each RCB class within each phenotype.
Results from the analysis indicated RCB index and classification was an accurate and consistent indicator of prognosis for all four breast cancer subtypes. RCB index also was tightly associated with prognosis over long-term follow-up. After five years, RCB-I patients had slightly worse EFS than pCR in HR- breast cancer and HR+/HER2+ breast cancer, but the same EFS as pCR in HR+/HER2- breast cancer.
“This pooled analysis confirms and expands upon prior findings that RCB index can predict risk of breast cancer recurrence,” said Symmans. “This assessment of prognostic risk can be used to accurately determine disease progression and inform treatment choice for breast cancer patients inclusive of all subtypes.”
Cancer centers do not all routinely collect data on RCB. “These findings indicate the importance of implementing residual cancer burden screening as a standard tool during cancer treatment. Routinizing RCB can give a more accurate sense of each patient’s prognosis, recurrence and best course of treatment while building an even more robust data set to improve understanding of the relationship between RCB index and long-term prognosis,” Symmans said.
The large numbers of patients in this study made it possible to observe that a precise estimate of future risk could be calibrated from the actual value of RCB index calculated from a person’s surgical resection specimen.
“This pooled analysis confirms and expands upon prior findings that RCB index can predict risk of breast cancer recurrence,” said Symmans. “This assessment of prognostic risk can be used to accurately determine disease progression and inform treatment choice for breast cancer patients inclusive of all subtypes.”
