n Abstract: Leptomeningeal disease is an uncommon complication of estrogen receptor positive breast cancer. While there is little consensus on the standard of care, recommendations from current clinical practice guidelines are to treat with intrathecal chemotherapy, necessitating invasive procedures and potentially resulting in a substantial incidence of serious complications and side effects. Here, we review all published evidence of the effectiveness of systemic hormonal therapy alone in treating this condition, with the advantage of requiring no invasive procedures and having virtually no serious complications or side effects. Evidence indicates that most hormonal therapies can penetrate the central nervous system and can be an effective treatment of endocrine sensitive breast cancer that is widely metastatic to the leptomeninges. n Key Words: breast cancer, endocrine therapy, ER-positive, leptomeningeal C linically, leptomeningeal disease (LMD) occurs in about 1-2% of all breast cancer. It most often occurs in patients with high grade estrogen receptor (ER)-negative infiltrating ductal carcinoma or low grade ER-positive infiltrating lobular carcinoma (1), though it can occur with any subtype. Whether this predisposition is due to factors related to cell shape, density, deformability, adhesion or other physical properties, or is related to the intrinsic molecular workings of the cell is unknown. Parsimony would favor a single, unifying explanation, but, since the known molecular biology of lobular and high grade ER-negative ductal tumors is disparate and cell morphology seen under the microscope for these two breast cancer types is also quite different, a unifying link remains a mystery. Whatever the underlying drivers, it remains challenging to treat. Here, we show an illustrative example of ER-positive LMD that responded dramatically to hormonal therapy, review all the published literature on the subject, and offer insights and implications from this experience.A 46-year-old premenopausal woman initially experienced radicular lower back pain and then weakness in her lower extremities. This progressed over 2 weeks and she could no longer stand and then had loss of urinary and bowel control. She was previously healthy.Neurologic exam showed that she could not stand or walk and there were with no patellar or Achilles reflexes. The breast exam was normal, as was the remainder of the physical exam. A lumbar puncture showed a protein of 1552 mg/dL, glucose 21 mg/dL and nucleated cells 388/dL with 98% being identified as lymphocytes. Cytology was not performed since a neoplasm was not initially suspected. Magnetic resonance imaging of the cervical, thoracic, and lumbar spine showed diffuse leptomeningeal enhancement of the cerebellar hemispheres, brainstem, spine, and cauda equina nerve roots (Fig. 1a). A presumptive diagnosis of infectious meningitis was made and intravenous antibiotics were started. All cultures and serologic tests remained negative however, and she did not clinically improve.Computerized tomogr...
