HER2-low lobular breast cancer with bone marrow involvement treated with T-DXd

What happened, in summary

This patient, a woman over 72, had previously undergone total mastectomy for lobular breast cancer. The original surgical specimen was ER-positive, PR-negative, and HER2-negative by IHC 0. She received adjuvant chemotherapy and then remained under long-term monitoring while taking letrozole, an aromatase inhibitor. For 8 to 9 years, there were no imaging or laboratory findings that suggested metastatic breast cancer. The later recurrence did not present as a visible organ mass. Instead, she developed thrombocytopenia, with platelet counts below 60,000, and mild anemia. Her clinicians evaluated her for a possible second hematologic malignancy, but bone marrow aspiration revealed breast cancer infiltration. The bone marrow disease showed low HER2 staining, creating a treatment situation different from the original HER2-negative tumor. Because standard options were limited for this revised HER2-low profile, she began T-DXd at 5.6 mg/kg intravenously every 21 days. The hematologic response came quickly: after 2 subsequent infusions, platelet and hemoglobin levels recovered. Recovery of both platelet and hemoglobin levels suggested that the marrow disease was responding to therapy. As of 2 years after starting T-DXd, she remained free of bone marrow disease and continued the same treatment regimen. Her course highlights a marrow-based relapse pattern in lobular breast cancer and a durable response after switching from endocrine maintenance to HER2-low-directed treatment. No other metastatic site was described in this marrow-focused relapse. The recovery of blood counts was clinically meaningful because thrombocytopenia and anemia had been the main warning signs of recurrent marrow disease during long-term follow-up.