Residual cancer burden predicts long-term outcomes across breast cancer subtypes
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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
Reference:
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.
Perspective
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Adam M. Brufsky, MD, PhD
Over the last several years, there has been a movement to incorporate residual cancer burden into the evaluation of women after neoadjuvant therapy. We have been using pathologic complete response forever, but residual cancer burden — which has been around for about 10 years — also takes into account the size of the tumor bed, how much cancer is left in the tumor bed, and the presence or absence of positive lymph nodes.
The MD Anderson group published follow-up of their own data in 2017, and it is great that they have now gone outside MD Anderson and applied this across a broad variety of institutions around the world.
These are really strong data. The analysis, based on a large number of cases, suggests residual cancer burden works very well. If you are RCB-0 — meaning pathologic complete response — you have the best prognosis. If you are RCB-I, your prognosis may be a little bit worse but it’s still really good. If you are RCB-II or RCB-III, your prognosis clearly is a lot worse.
We incorporate this in our center, which is a big academic institution that is kind of championing this. We report residual cancer burden probably 80% of the time for patients who receive neoadjuvant therapy. Hopefully, based on these data, it will be incorporated into a lot of other centers, as well. I think it will. I believe these results likely will promulgate the use of this tool to estimate prognosis.
The other interesting thing about this abstract — other than confirming what I think a lot of us suspected about residual cancer burden — is that the residual cancer burden status of hormone receptor-positive, HER2-negative disease actually was prognostic, and I don’t think any of us would’ve believed that. I think we’re going to have to think about that a little bit, but it may change a few minds about the use of neoadjuvant therapy in ER-positive disease.
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Hope S. Rugo, MD, FASCO
The cellularity of residual disease — meaning how dense your cells are in residual disease — is something oncologists haven’t really thought about very much. You either had a centimeter of disease left or you didn’t. Now, I think we are really going to be able to put that into context in terms of outcome, and that will affect how we treat our patients. In the postneoadjuvant setting, being able to stratify is incredibly important to affect outcomes and also to minimize toxicity for patients who actually have a very good outcome despite having minimal residual disease.
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