Nodular Regenerative Hyperplasia Suggested by Noninvasive Findings during Adjuvant Trastuzumab Emtansine Therapy for...

Trastuzumab emtansine (T-DM1) is the standard adjuvant therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with residual invasive disease after neoadjuvant chemotherapy. It is generally well tolerated. However, nodular regenerative hyperplasia (NRH), presenting as newly detected hepatic nodules, is a rare hepatic adverse event of T-DM1 that requires differentiation from liver metastasis. Here, we report a patient with HER2-positive breast cancer who developed new hepatic nodules during adjuvant T-DM1 therapy; NRH was suspected based on noninvasive findings.

A 58-year-old woman was referred for the evaluation of a right breast mass. Her past medical history was notable only for first-degree atrioventricular block, and her mother had a history of colon cancer. Imaging showed a 3.2-cm mass, and core needle biopsy revealed an invasive ductal carcinoma that was hormone receptor-positive and HER2-positive; the clinical stage was cT2N0M0 (stage IIA). She received neoadjuvant dose-dense doxorubicin/cyclophosphamide, followed by docetaxel plus trastuzumab and pertuzumab, and then underwent breast-conserving surgery with a sentinel lymph node biopsy. Residual invasive disease was identified (pathological complete response was not achieved). After whole-breast irradiation, T-DM1 and an aromatase inhibitor were administered as adjuvant therapy. After T-DM1 initiation, grade 1 transaminase elevation and grade 1 or 2 thrombocytopenia developed. Following 9 cycles of T-DM1, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI demonstrated new nodules in hepatic segments III and IV. Various hepatic lesions, including liver metastases and primary hepatic tumors, were considered in the differential diagnosis, but the imaging findings were atypical. T-DM1-associated NRH was also considered; however, at the patient's request, a liver biopsy was not performed, and the lesions were followed up with imaging. The patient completed 14 cycles of T-DM1. Post-treatment imaging revealed mild splenomegaly and a coarse hepatic parenchymal texture, suggestive of mild portal hypertension, while the hepatic nodules remained stable. One year after the completion of T-DM1, her liver enzyme levels and platelet counts improved, and there was no evidence of breast cancer recurrence.

When new hepatic nodules develop during adjuvant T-DM1 therapy, T-DM1-associated NRH should be considered in the differential diagnosis. Although histological confirmation is required for a definitive diagnosis, noninvasive findings such as thrombocytopenia, splenomegaly, atypical EOB-MRI findings, and lesion stability may raise suspicion of NRH and help distinguish it from liver metastases.