Characteristics and Treatment Obstacles in HER2-Positive PBSCC

Background

HER2-positive PBSCC is an exceptionally rare malignancy, constituting less than 0.1% of all breast carcinomas, with fewer than 100 cases reported globally. The rarity of this subtype leads to significant clinical challenges, including a lack of standardized treatment guidelines and limited data on therapeutic responses. Understanding the unique biology and treatment resistance of HER2-positive PBSCC is critical for developing effective management strategies. [1, 2, 3, 4]

Data Highlights

Key numerical data includes: HER2 positivity occurs in only 5.8-7.1% of PBSCC cases; the pathological complete response (pCR) rate for HER2-positive PBSCC to standard HER2-targeted therapy is only 12.5%; and a repeat biopsy revealed HER2 downregulation.

Key Findings

• HER2 positivity occurs in only 5.8-7.1% of PBSCC cases.
• The pathological complete response (pCR) rate for HER2-positive PBSCC to standard HER2-targeted therapy is only 12.5%.
• The patient exhibited a poor response to neoadjuvant TCHP therapy, with a Miller-Payne grade of 2.
• After mastectomy, local recurrence occurred within 3 months.
• Third-line treatment with trastuzumab deruxtecan (T-DXd) achieved a partial response, but progression-free survival was limited to 5 months.
• A repeat biopsy revealed HER2 downregulation, indicating antigen loss as a mechanism of acquired resistance.

Clinical Implications

The case illustrates the complexities in managing HER2-positive PBSCC. Clinicians should focus on the unique biological characteristics of the tumor and consider molecular profiling for treatment decisions.

Conclusion

This case highlights the complexities in managing HER2-positive PBSCC and the importance of understanding treatment resistance mechanisms.

Related Resources & Content

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6. Frontiers in Oncology — Primary large cell neuroendocrine carcinoma of the breast with metastasis in the lymph nodes: a case report and literature review
7. IARC Publications Website - Breast Tumours
8. NCCN Guidelines® Insights: Breast Cancer, Version 5.2025 - PubMed
9. Neoadjuvant Chemotherapy for Metaplastic Breast Cancer: Response Rates, Management, and Outcomes - ScienceDirect