Background: In human epidermal growth factor 2-positive breast cancer (HER2+BC), neoadjuvant chemotherapy and anti-HER2-targeted therapy (nCT) achieves a complete pathologic response (pCR) in 40-67% of patients. Posttreatment magnetic resonance imaging (pMRI) is considered the gold standard, with high specificity but lower sensitivity for assessing response. The authors previously determined that anti-HER2Th1 immune response is associated with pathologic response after nCT in HER2+BC patients. This study contrasted pMRI with anti-HER2Th1 response for assessing pCR in HER2+BC.
Methods: A retrospective review of HER2+BC patients at the authors' institution was performed. Original pMRI reports were collected, and images were reviewed by a breast radiologist blinded to pCR and immune response. The post-nCT imaging-based tumor response was assessed by Response Evaluation Criteria in Solid Tumors. The anti-HER2Th1 response was determined by ex vivo stimulation of peripheral blood mononuclear cells with six major histocompatibility complex (MHC) class 2-derived HER2 peptides via enzyme-linked immunospot (ELISPOT). Posttreatment MRI and anti-HER2Th1 responses were cross-tabulated with pCR. Standard diagnostic metrics were computed.
Results: For 30 patients, pMRI and anti-HER2Th1 immune response were measured, with 13 patients (43.3%) achieving pCR. The mean anti-HER2Th1 response in pCR was 167 (range 53-418), and <pCR was 24 (range 0.4-53). The distributions were nearly non-overlapping. The anti-HER2Th1 response was superior to the original pMRI and had higher accuracy than the blinded pMRI review (area under the curve 0.97 vs 0.55; sensitivity 100 vs 46.2%; specificity 94.1 vs 64.7%; overall accuracy 96.7 vs 56.7%).
Conclusion: The presence of a high anti-HER2Th1 response is superior to pMRI for the assessment of pCR in HER2+BC. This assay has considerable promise, and validation in a large-scale study is warranted.