Enhanced humoral immunity in breast cancer patients with high serum concentration of anti‐HER2 autoantibody

Humoral immunity plays a substantial role in the suppression of breast cancer. We have revealed that a high serum concentration of anti‐HER2 autoantibody (HER2‐AAb) is associated with favorable outcomes in patients with invasive breast cancer. Thus, we aimed to clarify the association between high serum concentration of HER2‐AAb and humoral immune response in the tumor microenvironment. Out of 500 consecutive patients with invasive breast cancer, we selected those whose HER2‐AAb values were high (n = 33) or low (n = 20) based on the distribution of HER2‐AAb values of 100 healthy individuals. Tumor and regional lymph node formalin‐fixed paraffin‐embedded samples prepared from the surgical specimens were subjected to immunohistochemistry. We confirmed that the recurrence‐free survival of the high HER2‐AAb group was significantly longer than that of the low HER2‐AAb group (p = 0.015). The numbers of tumor‐infiltrating CD20+ immune cells (ICs) (p < 0.001), IGKC+ICs (p = 0.023), and CXCL13+ ICs (p = 0.044) were significantly higher in the high HER2‐AAb group than in the low HER2‐AAb group. The number of CD4+ ICs in the B‐cell follicles of the regional lymph nodes was also significantly greater in the high HER2‐AAb group than in the low HER2‐AAb group (p = 0.026). Our findings indicate that a high level of HER2‐AAb is associated with enhanced humoral immunity against breast cancer and thus may provide a rationale for the association of HER2‐AAb with favorable prognosis.