Is Multiple Sclerosis a Risk for Hypercoagulation States or Breast Cancer? A Case Report and a Literature Review to Assess Options
Authors: Thomas Lisa , Shi Qi , Ramakrishnan Sathyanarayanan , Jia Jihua , Thomas-Hemak Linda 
Published: October 2019

Abstract
Abstract 4665

Introduction:
Multiple sclerosis (MS) is an autoimmune inflammatory and chronic demyelinating disease. Occurrence of hypercoagulable states and breast cancer in patients with multiple sclerosis (MS) has not been extensively reported. We report a case of a female MS patient with recurrent DVTs, elevated factor VIII levels, and advanced breast cancer with aggressive biologic phenotypes.

Case report:
A 45-year-old Caucasian female with a history of MS had a breast mass diagnosed on a screening mammogram. She was diagnosed with right breast carcinoma (2.5 × 2.5 × 1.6 cm), T2 N3 M0, which correlated to stage IIIC. She underwent a right modified radical mastectomy with 16/25 lymph nodes involved, ER/PR status was positive, HER-2/neu 0 with high Ki67. Her post-surgery treatment plan included 4 cycles of Cyclophosphamide and Taxotere chemotherapy. She also received chest wall radiation as well as tamoxifen and aromatase inhibitor (Femara) therapy. The patient had never been on hormone replacement therapy or oral contraceptives. She had bilateral salpingo-oophorectomy and hysterectomy and pathology was unremarkable. Patient was diagnosed with Multiple Sclerosis at age 27. She was treated with intermittent courses of steroids, Interferon b-1b, Interferon b-1a, and Mitoxantrone (MTX) for relapsing/remitting MS for several years until she developed left hemiparesis, hypoesthesias, and residual visual dysfunction that prompted her to start IVIG therapy and plasmapheresis. Past medical history presents recurrent DVT (in 2006) and elevations of coagulation factor VIII (355%). The patient also developed superior vena cava thrombosis in the presence of Lovenox and coumadin therapy.

Discussion:
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system, frequently complicated by devastating neurologic symptoms and progressive disability. Risks of DVT in bedridden or wheelchair-bound MS patients have been suggested. Previous studies show that the frequency of DVT in late-stage MS may be over 40%. Additionally, in MS patients without risk factors, it has been suggested with an autoimmune inflammatory disease that the inflammatory infiltration in MS plaques located close to small or medium-sized veins could have a role as well. The lumbar puncture could also be one of other thrombophilic factor in MS, since after dural puncture the decrease of cerebrospinal fluid pressure induces a rostrocaudal sagging effect with traumatic damage to the fragile venous endothelial wall and may trigger a venous vasodilatation with resultant stasis. Elevated factor VIII levels are a risk factor for venous thrombosis and may also be associated with the risk of arterial thrombosis in coronary heart disease. Studies show that factor VIII levels may be increased by chronic inflammation. However, elevated factor VIII levels in patients with MS have never been reported.
There is no cure for MS, though there are several drugs such as immunomodulatory agents that can slow or stop its progress. However, current data show a small increased risk of breast cancer in women with MS. The size of the breast tumor was also larger for woman with MS. More specifically, the proportions of biologically aggressive phenotypes that can worsen the prognosis of breast cancer incrementally despite the biologic phenotype at diagnosis also were investigated in this group of patients. One hypothesis linking breast cancer and MS involves long-term use of immunomodulatory agents including IFNs and glatiramer. Immunomodulatory therapy may impart immune system alterations that promote enhancement of cancer cells’ ability to evade immune recognition and cancer metastasis by altering the body’s ability to conduce immunosurveillance. However, consistent with previous observations, this remains unexplained and warrants further attention.

Conclusion:
The Female patient with MS described in this article presents an example of recurrent DVT, Superior Vena Cava thrombosis, elevated factor VIII levels, and breast cancer with stage IIIC and biologically aggressive phenotypes. The authors concern is that there is an increased risk of hypercoagulation states and breast cancer development in patients with MS. The systematic application of long-term preventive DVT may be considered for this group of patients.

Disclosures:
No relevant conflicts of interest to declare.