Breast Cancer Research and Treatment

, Volume 167, Issue 3, pp 771–778 | Cite as

Breast cancer-related paraneoplastic neurologic disease

  • Brittany L. Murphy
  • Nicholas L. Zalewski
  • Amy C. Degnim
  • Andrew McKeon
  • Eoin P. Flanagan
  • Sean J. Pittock
  • Elizabeth B. Habermann



Paraneoplastic neurologic disease (PND) is an aberrant immune-mediated response against the nervous system triggered by malignancy. Given the rarity, a paucity of data describing breast cancer-related PND (BC-PND) exists; we sought to further examine this specific patient population.


We retrospectively identified patients at our institution from 1997 to 2016 with BC-PND. Retrospective review with a descriptive analysis determined factors associated with PND and BC, which were compared to national breast cancer median of age (61 years) and average stage at diagnosis (60% local disease).


BC-PND was diagnosed in 56 female patients at a median age of 52.8 years. Only 20% of invasive cancer patients had local disease. The majority of patients were hormone receptor positive and Her2 negative. Neurological symptoms presented prior to BC diagnosis in 57.1% of patients. Of all patients, 30 (53.6%) had autoantibodies detected: Purkinje Cell Cytoplasmic Autoantibody Type-1 (PCA-1[anti-Yo]), n = 10; amphiphysin-IgG, n = 9; Anti-Neuronal Nuclear Autoantibody Type-2 (ANNA-2[anti-Ri]), n = 5; and others, n = 6. The most common neurologic findings were cerebellar ataxia, myelopathy, and myopathy. Immunotherapy benefit was found to be robust (21.6%), mild to moderate (52.9%), absent (17.6%), or indeterminate (7.8%).


PND symptoms often presented prior to BC diagnosis, with the BC biologic subtype characteristics typical of the general BC population. BC diagnoses were often made at younger ages than that of the general BC population and with later-stage disease. Roughly 75% of patients benefited from immunotherapy. These data provide helpful information to providers treating this population of patients.


Breast cancer Paraneoplastic neurologic disease Paraneoplastic syndrome 



Paraneoplastic neurologic disorder


Cerebrospinal fluid


Computed tomography


Positron emission tomography


Hormone receptor


Human epidermal growth factor 2




Acetylcholine receptor


Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor


Anti-Neuronal Nuclear Autoantibody Type-2


Glutamic acid decarboxylase, 65 kDa isoform


Neuromuscular junction


Purkinje Cell Cytoplasmic Autoantibody Type-1


Voltage-gated calcium channel


Interquartile range



The authors would like to acknowledge the support of the Mayo Clinic Departments of Neurology, Surgery, and the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery as substantial contributors of resources to the project.


The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery provides salary support for Drs. Habermann and Murphy. No external funding was used. This work has not previously been submitted for publication. This work was presented as a poster presentation at the American Society of Clinical Oncology Annual Meeting in Chicago, IL June 2017.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. The authors have no disclosures directly pertaining to this publication. SP has received no royalties to date, but may accrue revenue for patents relating to AQP4 antibodies for diagnosis of neuromyelitis optica and AQP4 autoantibody as a cancer marker. He receives research support from the Guthy-Jackson Charitable Foundation, Alexion Pharmaceuticals, Inc. and the National Institutes of Health (RO1 NS065829). AM receives research support from Medimmune, which does not relate to the data in this manuscript.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Brittany L. Murphy
    • 1
    • 2
  • Nicholas L. Zalewski
    • 3
  • Amy C. Degnim
    • 1
  • Andrew McKeon
    • 3
    • 4
  • Eoin P. Flanagan
    • 3
    • 4
  • Sean J. Pittock
    • 3
    • 4
  • Elizabeth B. Habermann
    • 1
    • 2
  1. 1.Department of SurgeryMayo ClinicRochesterUSA
  2. 2.The Robert D. and Patricia E. Kern Center for the Science of Health Care DeliveryMayo ClinicRochesterUSA
  3. 3.Department of NeurologyMayo ClinicRochesterUSA
  4. 4.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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