Anti-HER2 CD4+ T-Helper Type 1 Immune Response is Superior to Breast MRI for Assessing Response to Neoadjuvant Therapy in Patients with HER2-Positive Breast Cancer.

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.

• Authors: Lucy M De La Cruz, Elizabeth S McDonald, R Mick, Jashodeep Datta, Nadia F Nocera, Shuwen Xu, Carla S Fisher, Brian J Czerniecki
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 24 Issue 4 Pg. 1057-1063 (Apr 2017) ISSN: 1534-4681 [Electronic] United States
• PMID: 27826664 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Peptide Fragments
• Doxorubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Area Under Curve
• Breast Neoplasms (diagnostic imaging, drug therapy, immunology, metabolism)
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Enzyme-Linked Immunospot Assay
• Female
• Humans
• Immunity, Cellular
• Magnetic Resonance Imaging
• Middle Aged
• Molecular Targeted Therapy
• Neoadjuvant Therapy
• Paclitaxel (administration & dosage)
• Peptide Fragments (immunology)
• Predictive Value of Tests
• ROC Curve
• Receptor, ErbB-2 (antagonists & inhibitors, immunology, metabolism)
• Response Evaluation Criteria in Solid Tumors
• Retrospective Studies
• Th1 Cells
• Trastuzumab (administration & dosage)
• Young Adult