HER2-Positive Breast Cancer Linked to a Rare Immune-Related Neurological Syndrome

What happened, in summary

A 44-year-old woman entered early breast screening because her mother had died from metastatic breast cancer. In July 2018, mammography and MRI found several lesions in her left breast, the largest measuring 15 × 13 × 20 mm. Two biopsies showed multicentric invasive ductal carcinoma with different receptor patterns. One focus was grade 3, oestrogen-receptor negative, progesterone-receptor positive and HER2 3+, with Ki-67 of 45%. The other was grade 2, ER/PR negative and HER2 3+, with Ki-67 of 35%. Imaging showed no nodal or distant spread, and the disease was classified cT1N0M0. She received four cycles of doxorubicin and cyclophosphamide from September to November 2018, followed by paclitaxel, trastuzumab and pertuzumab. Soon after the first cycle of the second regimen, she developed severe gait instability and right-arm difficulty. Brain imaging and cerebrospinal-fluid testing excluded metastases, while anti-Yo antibodies in serum and CSF supported paraneoplastic cerebellar degeneration. She completed four cycles of HER2-directed treatment; paclitaxel was stopped after 11 doses because of peripheral neuropathy. Intravenous immunoglobulin was given for the neurological syndrome. In April 2019, skin- and nipple-sparing mastectomy with sentinel-node biopsy showed a pathologic complete response, ypT0N0, with all 7 nodes negative. She completed 1 year of trastuzumab and continued tamoxifen. At 1 year there was no evidence of recurrent breast cancer. Intensive rehabilitation restored independent walking, although balance problems and right-sided asymmetry remained.