Lucy M De La Cruz1,2, Elizabeth S McDonald1,2, R Mick3, Jashodeep Datta1,2, Nadia F Nocera1,2, Shuwen Xu1,2, Carla S Fisher1,2, Brian J Czerniecki4. 1. Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 2. Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 3. Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Breast Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USA. Brian.Czerniecki@moffitt.org.
Abstract
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.
BACKGROUND: In humanepidermal 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.