Residual cancer burden predicts long-term outcomes across breast cancer subtypes
SAN ANTONIO — Residual cancer burden after neoadjuvant chemotherapy accurately predicted long-term recurrence risk and survival across all breast cancer subtypes, according to results of a meta-analysis presented at San Antonio Breast Cancer Symposium.
“Any improved precision we can add to conversations about prognostic risk is extremely valuable,” W. Fraser Symmans, MD, professor and director of research operations in the department of pathology at The University of Texas MD Anderson Cancer Center, told Healio. “In a few short years, we have gone from ‘There’s nothing there’ to ‘There’s something there’ to basic and relatively crude categories — be they stage or residual cancer burden — to a future where we are starting to outline a mathematical formula that will provide a precise estimate.”
Several factors — including primary tumor size, lymph node involvement and percentage of the tumor that is invasive vs. in situ — contribute to assessment of residual cancer burden.
Single-institution studies have demonstrated that residual cancer burden after neoadjuvant chemotherapy can provide insights into a patient’s prognosis after surgery. Symmans and colleagues conducted their study to assess whether this held true for all subtypes, as well as how generalizable prior findings may be.
Symmans and colleagues from the I-SPY Clinical Trials Consortium analyzed data from approximately 5,100 patients from 12 cancer centers or clinical trials.
Investigators used a residual cancer burden calculator hosted by MD Anderson that assigns classifications of pathologic complete response, RCB-1 (minimal burden), RCB-II (moderate burden) or RCB-III (extensive burden).
Results showed tight and consistent associations across cancer centers and disease subtypes between residual cancer burden index and two key outcome measures: EFS and distant-recurrence free survival.
Highlights from the EFS analysis were as follows:
Among patients with hormone receptor-positive, HER2-negative disease, 11% were classified as having pathologic complete response, 11% were RCB-I, 53% were RCB-2 and 25% were RCB-III. At 10-year follow-up, 19% of those in the pathologic complete response group had developed recurrence or died, compared with 14% in the RCB-I group, 31% in the RCB-II group and 48% in the RCB-III group.
Among patients with hormone receptor-positive, HER2-positive, 38% of patients were classified as having pathologic complete response, 20% were RCB-I, 33% were RCB-II and 8% were RCB-III. At 10-year follow-up, 9% of patients in the pathologic complete response group had developed recurrence or died, compared with 17% in the RCB-I group, 36% in the RCB-II group and 55% in the RCB-III group.
Among patients with hormone receptor-negative, HER2-positive disease, 69% of patients were classified as having pathologic complete response, 11% were RCB-I, 16% were RCB-II and 4% were RCB-III. At 10-year follow-up, 7% of those in the pathologic complete response group had developed recurrence or died, compared with 15% in the RCB-I group, 37% of RCB-II group and 40% in the RCB-III group.
Among patients with hormone receptor-negative, HER2-negative disease, 43% of patients were classified as having pathologic complete response, 12% were in RCB-I, 33% were RCB-II and 11% were RCB-III. At 10-year follow-up, 14% of those in the pathologic complete response group had developed recurrence or died, compared with 25% in the RCB-I group, 39% in the RCB-II group and 75% in the RCB-III group.
The results demonstrate the residual cancer burden index is strongly prognostic and allows for recurrence risk to be measured with confidence, Symmans said. It also offers real-world evidence of how patients are responding to neoadjuvant treatments, and the correlation between residual cancer burden and prognostic risk can help the clinical team determine the optimal next steps in treatment for their patients, he added.
“For every disease subtype, there are post-neoadjuvant treatments approved or in trials,” Symmans told Healio. “This approach will not predict which treatments will work, but this information is a much better way for us to balance the estimated risk vs. the potential toxicities of these treatments.”
Researchers acknowledged limitations of their study. Use of data from multiple institutions can lead to variation in clinical methods and the manner in which samples are handled. In addition, some data on residual cancer burden were collected retrospectively and some were collected prospectively.
In addition, not every cancer center routinely collects data related to residual cancer burden; however, results of this study show that pathologists can implement it with accurate results, Symmans added.
“My estimate is that, at least in NCI-led clinical trials looking at post-neoadjuvant treatments, less than 10% of pathology reports would reported this,” Symmans said in an interview. “But, until now, there hasn’t been a 5,000-patient study to really demonstrate how this can work. So it’s anew page, and I think it’s a bit of a clarion call that we need to be more specific that the post-neoadjuvant specimen is not the same as a primarily surgically managed, untreated tumor, and we need a bespoke way of standardizing what we collect, with residual cancer burden being just one of them.” – by Mark Leiser
Yau C, et al. Abstract GS5-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosures: The study was funded by the Department of Defense, a NIH program grant, Cancer Prevention Research Institute of Texas and Breast Cancer Research Foundation. Symmans reports co-holding a pattern for a mathematical formula used in The University of Texas MD Anderson Cancer Center’s residual cancer burden index.