Paraneoplastic neurological complications of breast cancer

Abstract

Breast cancer is the most frequent cause of cancer of women in much of the world. In countries with screening programs, breast cancer is often detected before clinical symptoms are apparent, but occasionally the occurrence of a paraneoplastic syndrome precedes the identification of cancer. In breast cancer, there are known to be paraneoplastic endocrine syndromes and neurologic syndromes. The neurologic syndromes are often hard to identify and treat. The neurologic syndromes associated with breast cancer include cerebellar degeneration, sensorimotor neuropathy, retinopathy, stiff-persons syndrome, encephalitis, and opsoclonus–myoclonus. Most of these are mediated by antibodies against known neural antigens, although some cases appear to be mediated by non-humoral mechanisms. Treatments differ depending upon the syndrome type and etiology. Outcomes also vary depending upon duration of disease, the treatments used and the responsiveness of the underlying cancer. A thorough review of the published literature is provided along with recommendations for management and future research.

Paraneoplastic cerebellar degeneration with bilateral facial palsy: a rare primary presentation of breast cancer

“…Due to the dearth of prospective studies in the literature as a result of the rarity of the disease; no standard management protocol exists 27 28. The treatment of PCD is usually started on empirical basis and should be customised for each patient 27. The primary treatment includes surgical resection of the underlying tumour.…”

Paraneoplastic neurologic syndrome as a presentation of underlying breast malignancy

“…Antineuronal antibody development in paraneoplastic neurologic syndromes is detected in 60% of cases affecting the central nervous system (CNS) and 20% of cases within the peripheral nervous system . Antibodies typically fall into two categories: those that target intracellular antigens that are also present within the tumor and mediate disease through a cytotoxic T‐cell mechanism, and those that target extracellular neuronal antigens which often leads to an inflammatory response . As the latter exhibits pathogenicity via an inflammatory mechanism that occurs extracellularly, patients experience improvement with anti‐antibody treatments.…”

“…Breast cancer patients with anti‐Yo antibodies also more commonly have eye‐movement disorders and paraneoplastic retinopathy, which is usually secondary to cross reaction of a tumor‐surface antigen antibody with the retina . Because of the immunologically excluded nature of the retina, generation of antigens by a breast cancer can lead to self‐recognition of auto‐antigens, which then leads to pathogenicity .…”

Subcellular Localization of Cerebellar Degeneration-Related Protein 1

“…Paraneoplastic cerebellar degeneration (PCD) is a rare, cancer-associated, autoimmune and neurodegenerative disease characterized by severe cerebellar dysfunction (1). PCD is closely associated with breast and ovarian cancer and occurs as an autoimmune response elicited by ectopic expression of neural antigens by the cancer cells (2).…”

“…PCD is closely associated with breast and ovarian cancer and occurs as an autoimmune response elicited by ectopic expression of neural antigens by the cancer cells (2). Onconeural antibodies and cytotoxic T cells target both the cancer cells and the neurons that endogenously express these antigens, ultimately causing degeneration of neurons in the cerebellar cortex (1,3). Anti-Yo is the predominant onconeural antibody found in the serum and cerebrospinal uid of patients with PCD (4,5).…”