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Breast cancer-related paraneoplastic neurologic disease

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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).

Results

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%).

Conclusions

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.

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Abbreviations

PND:

Paraneoplastic neurologic disorder

CSF:

Cerebrospinal fluid

CT:

Computed tomography

PET:

Positron emission tomography

HR:

Hormone receptor

Her2:

Human epidermal growth factor 2

Ab:

Antibody

AChR:

Acetylcholine receptor

AMPAR:

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

ANNA-2[anti-Ri]:

Anti-Neuronal Nuclear Autoantibody Type-2

GAD65:

Glutamic acid decarboxylase, 65 kDa isoform

NMJ:

Neuromuscular junction

PCA-1[anti-Yo]:

Purkinje Cell Cytoplasmic Autoantibody Type-1

VGCC:

Voltage-gated calcium channel

IQR:

Interquartile range

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Acknowledgements

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.

Funding

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.

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Authors and Affiliations

  1. Department of Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA

    Brittany L. Murphy, Amy C. Degnim & Elizabeth B. Habermann

  2. The Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA

    Brittany L. Murphy & Elizabeth B. Habermann

  3. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Nicholas L. Zalewski, Andrew McKeon, Eoin P. Flanagan & Sean J. Pittock

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Andrew McKeon, Eoin P. Flanagan & Sean J. Pittock

Authors
  1. Brittany L. Murphy
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  2. Nicholas L. Zalewski
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  3. Amy C. Degnim
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  4. Andrew McKeon
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  5. Eoin P. Flanagan
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  6. Sean J. Pittock
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  7. Elizabeth B. Habermann
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Corresponding author

Correspondence to Elizabeth B. Habermann.

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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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Murphy, B.L., Zalewski, N.L., Degnim, A.C. et al. Breast cancer-related paraneoplastic neurologic disease. Breast Cancer Res Treat 167, 771–778 (2018). https://doi.org/10.1007/s10549-017-4566-0

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