HER2-positive breast cancer with brain metastases: responding well to T-DXd

What happened, in summary

This 56-year-old woman was diagnosed with left breast invasive ductal carcinoma that was ER-positive, PR-positive, and HER2-positive by IHC 3+. At diagnosis, the cancer was locally advanced, staged T3N1M0 / Stage IIIA. She first received neoadjuvant chemotherapy with 4 cycles of doxorubicin plus cyclophosphamide, followed by 4 cycles of trastuzumab, pertuzumab, and docetaxel. The breast and lymph-node disease had a clinical complete response. She then underwent left total mastectomy and left axillary lymph-node dissection, and the surgical pathology showed pathologic complete response. About 2 months after surgery, she started post-mastectomy radiotherapy, trastuzumab and pertuzumab every 3 weeks, and anastrozole. Nine months after surgery, while presenting for her 11th dose of trastuzumab and pertuzumab, she developed numbness from the top of her head through the right shoulder and weakness in her right hand. Brain MRI showed metastatic lesions in the left cerebellum, left frontal lobe, and medulla, while systemic CT showed no extracranial metastasis. Surgery was considered too risky because of the medullary lesion, and radiation carried concern for toxicity. After multidisciplinary discussion and shared decision-making, she started dexamethasone and T-DXd at 5.4 mg/kg. Her right-arm strength improved within days, sensory symptoms improved by day 10, and MRI at 3 weeks showed the medullary lesion shrinking. After 3 doses, all brain lesions had decreased further. At 6 months, 11C-methionine PET showed no avid uptake in the medullary lesion, so T-DXd was continued instead of stereotactic radiation. After 14 months and 19 doses of T-DXd, she had no symptomatic or radiological relapse and no severe treatment-related adverse events.