|LETTER TO THE EDITOR
|Ahead of print
Breast cancer associated with paraneoplastic cerebellar degeneration: A case series
Ilavarasi Vanidassane, Ajay Gogia, Vinod Raina, Priya Tiwari
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||11-Feb-2019|
|Date of Decision||03-Jun-2019|
|Date of Acceptance||03-Jun-2019|
|Date of Web Publication||14-Sep-2020|
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Paraneoplastic cerebellar degeneration (PCD) is a rare paraneoplastic syndrome characterized by subacute cerebellar ataxia, dysarthria, and vertigo. PCD is associated with gynecological, lung, breast cancers, and Hodgkin lymphoma., Even though the literature on breast cancer is growing, we still have limited knowledge of breast cancer with PCD., We describe 3 patients with breast cancer with PCD treated in the medical oncology department, at Bhim Rao Ambedkar - Institute of Rotary Cancer Hospital (BRA-IRCH), and we discuss its oncological implications.
The mean age of our patients was 51 years. They presented with subacute onset of cerebellar symptoms (ataxia, dysarthria, and vertigo) in Neurology Clinic. Initial evaluation for infective, autoimmune, and metabolic causes were negative. Paraneoplastic evaluation with antibody panel comprising anti-Yo, anti-Hu, anti-Tr, and anti-Ri antibody was ordered. Two patients had increased titers of anti-Yo and one had increased anti-Ri antibody. An initial course of steroid with methylprednisolone 1 gram intravenously was given for 1 week and tapered over a month for PCD with only minimal improvement. On further evaluation in our oncology clinic, breast cancer was detected in all 3 cases. All patients had a tumor size <5 cm (T1/2) with nodal involvement. They were managed according to the stage of the tumor. On the post-treatment follow-up, only one patient (case 2) had a meaningful improvement in neurological symptoms. Two patients died because of complications related to neurological dysfunction like progressive dysphagia and aspiration and sepsis because of bed sore despite complete remission of breast cancer. Only 1 patient continues to be alive and disease-free at 36 months with residual cerebellar involvement. The baseline characteristics and clinical outcome of the patients are tabulated in [Table 1].
PCD can herald malignant disease as in our series or can recur with tumor relapse or can appear during the treatment of malignancy. The random mutations in cancer cells lead to an increased neo-antigens expression, which mimics proteins expressed in Purkinje cells in the cerebellar cortex. This elicits antibody and T-cell response against tumor cells, which also acts against the neuronal cells, leading to PCD. All PCD may not be associated with raised antibody titers, but when present, adds significant diagnostic value. Breast cancer accounts for 10%–15% of all anti-Yo antibodies associated with PCD, and 50% of all anti-Ri antibodies associated with PCD. Anti-Yo is the most frequent antibody detected followed by anti-Ri in patients with breast cancer. Post-treatment fall in antibody titers does not correlate with neurological improvement. Anti-Ri antibody is associated with improved neurological response to treatment and has better survival. Our second case with anti-Ri had a long interval before the diagnosis of breast cancer, a better neurological and oncological outcome than anti-Yo associated with PCD. Reports suggest oncological outcomes are favorable in patients with PCD compared with normal patients. It is supported by the hypothesis that these tumors grow and metastasize less, because of a vigorous immune response against cancer cells and nervous system leading to the favorable outcome in PCD-associated cancer. Current treatment for PCD with immunomodulatory strategies such as corticosteroids, immunoglobulins, rituximab, plasmapheresis, and treatment of underlying malignancy has shown no meaningful benefit. These treatments may be beneficial when instituted early before the irreversible neuronal loss. The quality of life among patients with breast cancer having PCD is poor because of the residual neurological dysfunction. A study reported that the 2 most common cause of death in these patients are neurological sequelae or tumor progression. The median survival in breast cancer with PCD is 100 months. The overall prognosis of these patients depends on the tumor stage and the severity of damage of neuronal cells. In our series, median survival is 29 months; this poor outcome could be because of late presentation and diagnosis of PCD.
With existing literature, one can conclude that PCD is a presenting feature in a very small percentage of patients with breast cancer. Breast cancer with PCD is often diagnosed in a limited stage. It has no association with a particular hormonal profile. Anti-Yo is the most common antibodies in this population. In our small series, we observed that anti-Ri association has favorable neurological outcomes. Unlike reported, the survival of our patients was unfavorable when compared with patients with breast cancer without PCD and the common cause of death was neurological complications. Early identification, prompt neurological and oncological management, and long-term rehabilitation can prevent complications, improves quality of life, and outcome in patients with breast cancer having PCD.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Afzal S, Recio M, Shamim S. Paraneoplastic cerebellar ataxia and the paraneoplastic syndromes. Proc (Bayl Univ Med Cent) 2015;28:217-20.
Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008;7:327-40.
Fanous I, Dillon P. Paraneoplastic neurological complications of breast cancer. Exp Hematol Oncol 2016;5:29.
Yan L, Dong X, Xu H, Huang J, Wang W, Huang L, et al
. Paraneoplastic cerebellar degeneration associated with breast cancer: A case report and review of the literature. Mol Clin Oncol 2018;9:163-7.
Vernino S. Paraneoplastic cerebellar degeneration. Handb Clin Neurol 2012;103:215-23.
Shams'ili S, Grefkens J, Bent VD, Hooijkaas H, Holt VD, Vecht C, et al
. Paraneoplastic cerebellar degeneration associated with antineuronal antibodyies: Analysis of 50 patients. Brain 2003;126:1409-18.
Rojas I, Graus F, Keime-Guibert F, Reñé R, Delattre JY, Ramón JM, et al
. Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies. Neurology 2000;55:713-5.