Spindle Cell (Metaplastic) Carcinoma of the Breast Showing No Clinical Benefit with Pembrolizumab-Based Neoadjuvant...

Metaplastic carcinoma (MC) of the breast is a rare subtype that is frequently chemoresistant, and clinical evidence for immune checkpoint inhibitor (ICI) therapy remains limited. Here, we report a case of spindle cell carcinoma (SpCC) MC showing primary resistance to neoadjuvant chemo-immunotherapy and describe features associated with the tumor immune microenvironment.

A woman with a 10-year history of a left breast mass presented with rapid enlargement to approximately 7 cm. Core needle biopsy revealed SpCC that was negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, with a high Ki-67 labeling index. Imaging suggested ipsilateral axillary nodal involvement, and neoadjuvant pembrolizumab combined with platinum/taxane chemotherapy was initiated. However, after 2 cycles, the tumor further enlarged with ulceration and protrusion from the prior biopsy site, consistent with progressive disease, and the patient underwent total mastectomy with axillary dissection. Histologically, the tumor consisted of high-grade atypical spindle cells with necrosis and minimal treatment effect. Immunohistochemistry demonstrated strong expression of programmed death-ligand 1 in both tumor and immune cells and increased CD8+ T-cell infiltration after therapy. By contrast, tumor cells showed significantly downregulated human leukocyte antigen (HLA)-A/B/C and β2-microglobulin, suggesting impaired antigen presentation. Increased CD163/CD204/triggering receptor expressed on myeloid cells 2-positive tumor-associated macrophages and focal transforming growth factor-β expression were also observed.

These findings suggest that HLA class I downregulation may contribute to ICI resistance.