Comparison of residual cancer burden, American Joint Committee on Cancer staging and pathologic complete response in breast cancer after neoadjuvant chemotherapy: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657)

Abstract

Purpose Several pathologic staging systems characterize residual tumor in patients undergoing neoadjuvant chemotherapy for breast cancer. Pathologic complete response (pCR) is now accepted by the Food and Drug Administration as an endpoint for granting accelerated drug approval. Two other systems of post-neoadjuvant pathologic tumor staging—Residual Cancer Burden (RCB) and the American Joint Committee on Cancer post-neoadjuvant therapy staging system (yAJCC)—have been developed to characterize residual tumors when patients do not achieve pCR. The optimal system, and the ways in which these systems complement each other, have not been fully determined. Methods Using data from the I-SPY 1 TRIAL, we compared pCR, RCB and yAJCC as predictors of early recurrence-free survival (RFS) to identify ways to improve post-neoadjuvant pathologic evaluation. Results Among 162 patients assessed, pCR identified patients at lowest risk of recurrence, while RCB and yAJCC identified patients at highest risk. Hormone-receptor (HR) and HER2 subtypes further improved risk prediction. Recursive partitioning indicated that triple negative or HER2+ patients with yAJCC III or RCB 3 have the highest recurrence risk, with an RFS of 27%. Our analysis also highlighted discrepancies between RCB and yAJCC stratification: 31% of patients had discrepant RCB and yAJCC scores. We identified differential treatment of lymph node involvement and tumor cellularity as drivers of these discrepancies. Conclusions These data indicate that there is benefit to reporting both RCB and yAJCC for patients in order to identify those at highest risk of relapse.

Breast specimen handling and reporting in the post-neoadjuvant setting: challenges and advances

“…Both systems show the strongest association with recurrence-free survival in triple-negative breast cancers, while hormone receptor positive cancers have relatively low recurrence rates regardless of RCB or yAJCC class 62. Patients who are RCB-3 or yAJCC3 and have triple negative or HER2+ tumours have a higher risk of relapse than all other patients 62. The study also found that in 34% of cases, RCB and yAJCC staging systems are discrepant and this is attributed to unequal weighting of positive lymph nodes and the weighting of tumour cellularity in RCB.…”

“…A recent study compared the RCB and the AJCC staging systems using the I-SPY 1 trial dataset 62. This study used the seventh edition of yAJCC staging system; however, this should not have impacted the anatomical TNM tumour staging based on the eighth edition.…”

“…This study used the seventh edition of yAJCC staging system; however, this should not have impacted the anatomical TNM tumour staging based on the eighth edition. Both systems identify patients with intermediate (4-fold) risk of relapse (RCB-1–2 and yAJCC1–2) and high (11-fold) risk of relapse (RCB-3 and yAJCC3) 62. Both systems show the strongest association with recurrence-free survival in triple-negative breast cancers, while hormone receptor positive cancers have relatively low recurrence rates regardless of RCB or yAJCC class 62.…”

“…Both systems identify patients with intermediate (4-fold) risk of relapse (RCB-1–2 and yAJCC1–2) and high (11-fold) risk of relapse (RCB-3 and yAJCC3) 62. Both systems show the strongest association with recurrence-free survival in triple-negative breast cancers, while hormone receptor positive cancers have relatively low recurrence rates regardless of RCB or yAJCC class 62. Patients who are RCB-3 or yAJCC3 and have triple negative or HER2+ tumours have a higher risk of relapse than all other patients 62.…”

“…The study also found that in 34% of cases, RCB and yAJCC staging systems are discrepant and this is attributed to unequal weighting of positive lymph nodes and the weighting of tumour cellularity in RCB. In discrepant cases, however, if one classification system identifies a patient as having a high risk of recurrence, then that patient tends to have an increased rate of recurrence regardless of the other system’s ranking 62. Therefore, there is benefit to computing both scores for patients in order to identify those with the highest risk of relapse.…”