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.
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%).


CONCLUSIONS
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.
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Lucy M
LM
De La Cruz
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Elizabeth S
ES
McDonald
Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
R
R
Mick
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Jashodeep
J
Datta
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nadia F
NF
Nocera
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Shuwen
S
Xu
Rena Rowan Breast Center, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.|Department of Endocrine and Oncologic Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Carla S
CS
Fisher
Department of Breast Oncology, H Lee Moffitt Cancer Center, Tampa, FL, USA. Brian.Czerniecki@moffitt.org.
Brian J
BJ
Czerniecki
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D010446:Peptide Fragments / Q000276:immunology; D011237:Predictive Value of Tests; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D066066:Response Evaluation Criteria in Solid Tumors; D012189:Retrospective Studies; D018417:Th1 Cells; D000068878:Trastuzumab / Q000008:administration & dosage; D055815:Young Adult
D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human