HER2-positive breast cancer: brain recurrence, T-DXd liver injury, and later progression

What happened, in summary

This 49-year-old premenopausal woman was referred for breast imaging after sudden enlargement and tenderness of the right breast with nipple retraction. Mammography and ultrasound in July 2021 were compatible with carcinomatous mastitis. Core breast biopsy and axillary-node cytology showed grade 3 infiltrative breast carcinoma, no special type, with HER2 IHC 3+ positivity and hormone receptor negativity. PET/CT showed locally advanced disease without distant metastases. She received weekly paclitaxel, trastuzumab, and pertuzumab from August 2021 to February 2022, with partial radiologic response. On 14 March 2022, she underwent radical right mastectomy. Pathology showed only rare foci of intraductal carcinoma and micrometastasis in 1 of 12 axillary nodes. She then received right chest wall and nodal radiotherapy, 40.05 Gy in 15 fractions. Because residual disease left her at high recurrence risk, she entered the ASTEFANIA trial and received T-DM1 with atezolizumab/placebo, but treatment stopped after 2 cycles because of hyperbilirubinemia. She completed trastuzumab in February 2023. One month later, confusion, dysarthria, and headache led to CT and MRI findings of 6 brain metastases. She received mannitol, dexamethasone, and stereotactic radiotherapy, then started T-DXd. T-DXd was dose-reduced and then stopped after severe liver enzyme elevation and biopsy-supported drug-induced liver injury. Later treatment included carboplatin/trastuzumab, trastuzumab alone, and reduced-dose weekly paclitaxel with trastuzumab after thoracic nodal progression. She died at home in December 2024 while followed by palliative care. Her liver workup included MRI, viral and autoimmune testing, hepatology review, and ultrasound-guided liver biopsy, which supported drug-induced liver injury and forced a major change in systemic treatment.