Residual Cancer Burden After Neoadjuvant Chemotherapy can be a Predictor of Breast Cancer Outcomes

Results from a large meta-analysis of 5,100 breast cancer patients, funded by the Department of Defense, the National Institutes of Health (NIH), the Cancer Prevention Research Institute of Texas, and the Breast Cancer Research Foundation, demonstrated that residual cancer burden after neoadjuvant chemotherapy is an accurate long-term predictor of recurrence and survival across all breast cancer subtypes.

This conclusion is based on data presented at the 42nd San Antonio Breast Cancer Symposium (SABCS), held in San Antonio, Texas, December 10 – 14, 2019.

“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 lead author, W. Fraser Symmans, MD, professor and director of research operations, Department of Pathology, at The University of Texas MD Anderson Cancer Center in Houston, Texas.

“We undertook this meta-analysis to help determine whether this is true for all subtypes, and how generalizable previous findings might be,” Symmans added.

Residual cancer burden
The residual cancer burden (RCB) is assessed through several factors, including routine pathologic sections measuring the size of the primary tumor, the percentage of the tumor that is invasive versus in situ, and the involvement of regional lymph nodes after completion of neoadjuvant therapy, Symmans explained.

Calculator
A calculator hosted by MD Anderson Cancer Center calculates residual cancer burden index and assigns a classification of pathologic complete response (pCR), RCB-I (minimal burden), RCB-II (moderate burden), or RCB-III (extensive burden).

Symmans, who co-holds a patent for a mathematical formula used in MD Anderson’s RCB index, 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 event-free survival (EFS) and distant recurrence-free survival (DRFS).

The residual cancer burden index was tightly associated with both EFS and DRFS, and was consistent across 12 clinical sites and all four types of breast cancer. In terms of EFS, the analysis of RCB categories showed:

• For hormone receptor (HR)-positive/HER2-negative, 11% of patients were classified as having a pCR, 11 percent as RCB-I, 53% as RCB-II, and 25% as RCB-III. At the 10-year follow-up, 19% of the pCR 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;
• For HR-positive/HER2-positive, 38% of patients were classified as having a pCR, 20% as RCB-I, 33% as RCB-II, and 8% as RCB-III. At the 10-year follow-up, 9% of the pCR 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;
• For HR-negative/HER2-positive, 69% of patients were classified as having a pCR, 11% as RCB-I, 16% as RCB-II, and 4% as RCB-III. At the 10-year follow-up, 7% of the pCR 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;
• For HR-negative/HER2-, 43% of patients were classified as having a pCR, 12% as RCB-I, 33% as RCB-II, and 11% as RCB-III. At the 10-year follow-up, 14% of the pCR 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.

“The measurement of RCB index is strongly prognostic, allowing us to measure risk of recurrence with confidence,” Symmans said.

“This meta-analysis of residual cancer burden provides real-world evidence of how patients are responding to neoadjuvant treatments, and calibration of RCB index to prognostic risk enables us to determine the most appropriate next steps for breast cancer patients,” he added.

Standardize reporting
Symmans also 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.

Discussing the limitations of the study, Symmans noted that the study, is based on data from multiple institutions. This, in his opinion, could lead to some variation in clinical methods, the handling of specimens, and possible other factors. He also noted that some data on residual cancer burden were collected prospectively and that other data was 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,” Symmans concluded.

Reference
Yau C, Van der Noordaa M, Wei J, Osdoit M, Reyal F, Hamy A, Lae M, Martin M, Del Monte M, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis. GS5-01. Presented at the 42th San Antonio Breast Cancer Symposium, held December 10 – 14, 2019 in San Antonio, Texas. [Abstract]