HER2-positive breast cancer with metastatic recurrence and complete response to T-DM1

What happened, in summary

This 43-year-old woman was first diagnosed 7 years earlier with grade 3 invasive breast carcinoma that overexpressed HER2 by IHC 3+ and was hormone receptor-negative. Initial staging was cT2N+ cM0. She received neoadjuvant doxorubicin plus cyclophosphamide every 3 weeks for 4 cycles, followed by docetaxel plus trastuzumab every 3 weeks for 4 cycles. She then underwent lumpectomy, with pathology showing ypTisN0 disease, followed by adjuvant radiotherapy and trastuzumab every 3 weeks to complete 1 year of HER2-directed treatment. After 3.5 years of surveillance, metastatic recurrence appeared as an ipsilateral major pectoralis muscle lesion with lung and broncho-hilar lymph-node metastases. Biopsy confirmed breast carcinoma metastasis that still showed HER2 overexpression and hormone receptor negativity. No liver metastases were found. She started first-line palliative T-DM1 at 3.6 mg/kg. During the first 6 months, CT showed a complete radiologic response. Treatment was complicated by persistent liver-enzyme abnormalities, rising bilirubin, thrombocytopenia, portal vein enlargement, splenomegaly, and elevated hepatic venous pressure. Liver biopsy findings supported T-DM1-related porto-sinusoidal vascular disorder, so T-DM1 was reduced twice and then stopped after 22 months. She began low-dose spironolactone and furosemide. Liver enzymes and bilirubin normalized within 3 months, though thrombocytopenia persisted. Seven months after stopping T-DM1, MRI showed portal-vein enlargement and esophageal varices, but she remained asymptomatic, without ascites or encephalopathy, and had no signs of recurrent breast cancer under active surveillance. An attempted upper endoscopy was not tolerated without sedation and was awaiting rescheduling, while surveillance for breast cancer recurrence continued during ongoing active follow-up.