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.
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yukiko
Y
Tabuchi
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan. mshimoda@onsurg.med.osaka-u.ac.jp.
Masafumi
M
Shimoda
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Naofumi
N
Kagara
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Yasuto
Y
Naoi
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Tomonori
T
Tanei
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Atsushi
A
Shimomura
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kenzo
K
Shimazu
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Seung Jin
SJ
Kim
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Shinzaburo
S
Noguchi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000453:epidemiology* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D001323:Autoantibodies; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Autoantibodies; Enzyme-linked immunosorbent assay; HER2; Humoral immunity; Immunotherapy