1. Samson, Kurt

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Using a breast cancer patient's residual cancer burden after they have undergone postoperative neoadjuvant chemotherapy appears to be an effective prognostic indicator for both long-term tumor recurrence and survival, regardless of cancer subtype, researchers told attendees at the 2019 San Antonio Breast Cancer Symposium (Abstract GS1-09).


A pooled analysis performed on patient data from 11 cancer institutes and clinical trials was used to assess whether or not residual cancer burden (RCB) index-based primary tumor size, percentage of tumor that is invasive, and involvement of lymph nodes, as well as other clinical and individual risk characteristics such as age, T category, nodal status, and grade-might predict outcomes as earlier research has indicated.


The index was found to be very accurate in predicting both event-free and distant recurrence-free survival (EFS and DRFS). Moreover, the findings were consistent across clinical sites and predictive for all four breast biological cancer subtypes, noted William Fraser Symmans, MD, the study's lead author, at a press conference.


The findings support a number of other studies that have likewise found accurate prognostics using residual cancer burdens as a means of estimating the trajectory of breast cancer patients as they recover.

William Fraser Symma... - Click to enlarge in new windowWilliam Fraser Symmans, MD. William Fraser Symmans, MD

"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 Symmans, Professor and Director of Research Operations at The University of Texas MD Anderson Cancer Center's Department of Pathology. "We undertook this meta-analysis to help determine whether this is true for all subtypes, and how generalizable previous findings might be."


They analyzed data on 5,161 breast cancer patients who had been treated at 11 cancer centers or had participated in clinical trials, using mixed effect models that included both fixed and random events. There were 950 EFS and 876 DRFS events during follow-up (median 65 months).


Symmans and his colleagues with the I-SPY Clinical Trials Consortium next used a special calculator created at MD Anderson to evaluate each patient's RCB index value. Results from the 10-year follow-up analysis were then used to classify each patient's status as RCB-I (minimal burden), RCB-II (moderate burden), or RCB-III (extensive burden). Once categorized, the team then compared each patient's RCB status with the pathologic complete response (pCR) rates for each category.


Subtype Analysis

At 10 years, 69 percent of patients were classified as having a pCR, including 11 percent within the RCB-I category, 16 percent classified as RCB-II, and 4 percent who were determined to have had RCB-III. Seven percent of the pCR group had a recurrence or had died, compared with 15 percent of the RCB-I group, 37 percent of the RCB-II group, and 40 percent of those in the RCB-III category.


For patients with HR-negative/HER2-positive breast cancer, 43 percent had a pCR at 10 years, including 12 percent of women with an RCB-I rating, 33 percent of those rated as RCB-II, and 11 percent of those in the RCB-III group. After a decade, 14 percent of the pCR group had had a recurrence or had died, including 25 percent of the RCB-I group, 39 percent of RCB-II women, and 75 percent of patients in the RCB-III group.


Among women with HR-positive/HER2-negative cancer, 11 percent had a pCR and their 10-year EFS rate was 86 percent, which fell as RCB index increased. Among the other patients, 11 percent were classified as RCB-I, 53 percent as RCB-II, and 25 percent as RCB-III. In all, 19 percent of the pCR group had a recurrence or had died, compared with 14 percent of the RCB-I group, 31 percent of the RCB-II group, and 48 percent of the RCB-III group.


For patients with HR-positive/HER2-positive cancer, 38 percent of were determined to have had a pCR, including 20 percent of those women classified as RCB-I, as well as 33 percent of those rated RCB-II and 8 percent rated RCB-III. At the 10-year follow-up, 9 percent of the pCR group had a recurrence or had died, compared with 17 percent of the RCB-I group, 36 percent of the RCB-II group, and 55 percent of the RCB-III group.


"The measurement of the RCB index is strongly prognostic, allowing us to measure risk of recurrence with confidence," said Symmans. "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 noted that, although not all cancer centers routinely collect data on residual cancer burden, the new review and analysis demonstrates that pathologists can use this technique to get relatively accurate results to predict recurrence in women across different breast cancer subtypes.


However, the study was not without limitations, Symmans said. These included the fact that the findings were based on data from multiple institutions, which can lead to some variation in clinical methods, the handling of specimens, and other potential factors. Moreover, some of the RCB data were collected prospectively while others were collected retrospectively.


"Long-term prognosis after pCR was similarly excellent in all phenotypic subtypes. RCB index and classification was independently and strongly prognostic in all subtypes, and generalizable to multiple practice settings," Symmans said. "Looking ahead, if we can standardize the reporting of residual cancer burden, that will only improve its usefulness in determining long-term prognosis."


Kurt Samson is a contributing writer.