Protective effect of naturally occurring anti-HER2 autoantibodies on breast cancer

Anti-HER2-autoantibodies (HER2-AAbs) are found in breast cancer patients as well as healthy individuals. However, the clinical relevance of the antibodies is unknown. We established an enzyme-linked immunosorbent assay with high sensitivity and quantified serum HER2-AAbs in 100 healthy women, 100 untreated patients with ductal carcinoma in situ (DCIS), and 500 untreated patients with invasive breast carcinoma (IBC). The associations between the levels of HER2-AAbs and breast cancer risk, and recurrence-free survival, were examined. High levels of HER2-AAbs were significantly associated with a reduced risk of DCIS (odds ratio [OR] 0.19, P = 4.6 × 10⁻⁷) or IBC (OR 0.31, P = 3.7 × 10⁻⁷). Subgroup analysis of IBC revealed a stronger association of HER2-AAbs with a reduced risk of the hormone receptor (HR)⁻/HER2⁺ subtype (OR 0.12) than the other subtypes (HR⁺/HER2⁻ [OR = 0.32], HR⁺/HER2⁺ [OR 0.38], and HR⁻/HER2⁻ [OR 0.29]). When we set the cutoff of HER2-AAbs at 20 ng/mL, recurrence-free survival of HER2-AAb-positive patients (N = 74) was significantly better than that of HER2-AAb-negative patients (N = 426) (P = 0.015). Univariate and multivariate analyses demonstrated that HER2-AAbs, as well as histological grade, were independently and significantly (P = 0.0065 and 0.049, respectively) associated with recurrence-free survival. Our exploratory study suggests a protective effect of naturally occurring HER2-AAbs on the development of primary and recurrent breast cancer. Further studies on HER2-AAbs are warranted.