Case Report: response of HER2-positive ductal carcinoma in situ to osimertinib with supporting in vitro evidence.

Ductal carcinoma in situ (DCIS) carries a risk of progression to invasive ductal carcinoma (IDC), and local treatments such as mastectomy and radiation therapy are commonly used. This case report describes a 74-year-old Japanese woman with concurrent HER2-positive DCIS and non-small cell lung cancer (NSCLC) with EGFR mutation who showed a remarkable response to osimertinib, an epidermal growth factor receptor inhibitor used to treat NSCLC. At initial presentation, the breast lesion measured 28 × 11 × 29 mm. Biopsy revealed high-grade DCIS with a HER2-immunohistochemistry score of 3+ and a Ki-67 index of 20-30%. The NSCLC was subsequently resected, and adjuvant osimertinib therapy was initiated postoperatively. Two months after treatment initiation, a right mastectomy was performed. Postoperative pathological examination showed a marked reduction in tumor size to 8 × 3 mm and a marked decrease in Ki-67 to 1%. These findings indicated multiple post-chemotherapy changes, with only a small amount of high-grade DCIS remaining, suggesting a therapeutic effect of the lung cancer treatment. Assessment of the inhibitory effect of osimertinib on HER2 in vitro demonstrated that osimertinib inhibited cell proliferation in a HER2 expression-dependent way. Western blotting also suggested the inhibition of HER2 phosphorylation. Therefore, these findings suggest that the remarkable response of HER2-positive DCIS in this case may be attributable to the HER2-inhibitory effect of osimertinib. Further research is warranted to determine whether osimertinib could serve as a potential treatment option for HER2-positive breast cancer, including DCIS.