Latest updates on antiretinal autoantibodies associated with vision loss and breast cancer

Abstract

Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic disorder of the retina that is frequently associated with breast cancer in pre- and postmenopausal women older than 50 years. In this review, we will give an update on the current knowledge regarding the association of antiretinal autoantibodies with the breast-CAR syndrome. Women with breast cancer and visual indications of CAR have a significantly increased incidence of autoantibodies (AAbs) against retinal proteins when compared to healthy women. The onset of visual loss in association with antiretinal AAbs peaks 2 to 3 years after the clinical diagnosis of breast cancer. Differences in severity of symptoms between women with or without antiretinal AAbs are evident, revealing more unfavorable presentation in seropositive women. The incidence of CAR in breast cancer is likely to rise as the survival time of patients with breast cancer increases; consequently, a prediction of breast-CAR based on autoimmunity to individual retinal antigens, or to panels of antigens (signatures), is clinically important.

Keywords: autoantibodies; breast cancer; cancer-associated retinopathy; enolase; retina.

Figure 1

Breast–cancer-associated retinopathy. (A) Distribution of patients with different kind of cancers and ocular symptoms indicative of cancer-associated retinopathy studied at Ocular Immunology Laboratory during the past 20 years (n = 546). Note that breast cancer is the most frequent (22%) in this cohort as compared to other malignancies. (B) Increase in frequency of breast-CAR from 3% in 1995 to 28% in the last 2 years (n = 122). y-axis represents the percentage of patients with cancer.

Figure 2

Schematic diagram of anti-tumor antibodies in formation process during carcinogenesis. Paraneoplastic autoantibodies may develop years before clinical presentation of breast cancer.

Figure 3

Latency time from the diagnosis of cancer to the manifestation of symptoms of breast-CAR and detection of antiretinal autoantibodies. Note that in some women visual symptoms and antiretinal autoantibodies precede the diagnosis of breast cancer by 4 years.

Figure 4

Distribution of antiretinal autoantibodies in breast-CAR group and controls. Patients with CAR developed antibodies against 27 different retinal proteins as opposed to 12 proteins by control subjects. x-axis shows retinal proteins marked by their molecular weights (k = 1000). y-axis represents the percentage of patients with AAbs reacting with specific proteins.

Figure 5

Immunostaining of ductal breast carcinoma with serum specific to anti-enolase autoantibodies. Brown color indicates anti-enolase positive cross-reactivity.