A durable response to trastuzumab in heavily pretreated metastatic breast cancer

What happened, in summary

A 63-year-old woman had first been diagnosed with estrogen- and progesterone-receptor-positive invasive ductal carcinoma of the left breast 28 years earlier. She underwent modified radical mastectomy and axillary dissection, followed by five years of tamoxifen. Six years later, an axillary recurrence was treated with cyclophosphamide, doxorubicin, and 5-fluorouracil, radiation, and anastrozole.

Metastatic disease later developed in the lungs and chest lymph nodes. Exemestane controlled the cancer for approximately 15 years before new liver metastases appeared. A liver biopsy showed ER- and PR-negative disease with HER2 IHC 1+ and no amplification. She received gemcitabine and carboplatin, radiation to liver and bone metastases, clinical-trial capecitabine, paclitaxel, further liver radiation, eribulin, and liposomal doxorubicin. Responses were temporary, followed by repeated liver and bone progression.

A later liver biopsy showed weak ER and PR expression, HER2 IHC 1+ without amplification, Ki-67 of 30%–40%, and an ERBB3 p.E928A mutation. Molecular and protein studies showed activation of HER2/HER3 signaling. Her team selected trastuzumab despite the absence of HER2 amplification. She began trastuzumab alone, and capecitabine was added after two cycles as blood counts and liver function improved.

The response was rapid. Bone pain, abdominal distention, and fatigue improved, tumor markers fell substantially, and imaging confirmed a partial response. She continued to benefit from trastuzumab-based treatment for more than 10 months while remaining under precision-oncology follow-up.