PS5-06-03: Early-stage hormone receptor-positive metaplastic breast cancer treated with chemo-immunotherapy: a case report

Abstract Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype, accounting for less than 1% of all breast cancers. It is characterized by two or more histological types, usually mixed epithelial and mesenchymal differentiation. MpBC typically presents with rapidly growing tumors and poor response to standard therapies. The majority of MpBCs are triple-negative. Hormone receptor-positive MpBC is exceptionally rare. Due to the rarity of this subtype, no MpBC-specific treatment guidelines exist. According to current NCCN recommendations, MpBC should be managed similarly to invasive ductal carcinoma of corresponding receptor status. However, outcomes remain significantly worse, with higher rates of chemoresistance, recurrence and distant metastasis. Emerging evidence suggests that PD-L1 expression is present in up to 95% of metaplastic breast cancers, supporting the rationale for incorporating immune checkpoint blockade into treatment. Case: A 54-year-old Hispanic woman presented with a painful, enlarging right breast mass. Diagnostic breast imaging revealed a 7.3 × 4.6 × 5.6 cm irregular, heterogeneously enhancing mass in the superior right breast, along with enlarged level 1 right axillary lymph nodes. Biopsy of the mass confirmed invasive metaplastic carcinoma with focal squamous differentiation, Grade 3, ER positive 84%, PR negative, HER2 IHC 1+, and Ki-67: 67%. Right axillary lymph node biopsy demonstrated benign lymph node tissue. Staging scans showed no evidence of distant metastases. The disease was staged as clinical stage IIIA (cT3, cN0, cM0). MammaPrint testing revealed MammaPrint Ultra High risk (MP2), qualifying her for enrollment in SWOG S2206, a randomized phase III trial evaluating neoadjuvant Durvalumab plus chemotherapy versus chemotherapy alone for adults with MammaPrint ultrahigh (MP2) hormone receptor (HR) positive / human epidermal growth factor receptor (HER2) negative stage II-III breast cancer. She was randomized to the standard chemo-immunotherapy arm, receiving 12 weeks of weekly paclitaxel, followed by dose-dense doxorubicin and cyclophosphamide every 2 weeks for 4 cycles, in combination with durvalumab every 2 weeks. To date, she has reported good treatment tolerance. Further clinical, radiographic, and pathological response assessment is pending and will be presented at the time of the symposium. This case highlights a rare histological subtype of hormone receptor-positive breast cancer and explores the potential role of chemo-immunotherapy in this biologically aggressive disease within the context of a clinical trial. A small prospective study from Memorial Sloan Kettering Cancer Center (MSKCC) demonstrated higher pathologic complete response rates in patients with triple-negative metaplastic breast cancer treated on the KEYNOTE-522 regimen. However, data on the role of immunotherapy in hormone receptor-positive MpBC remain limited. This case may contribute to a better understanding of the potential role of adding immunotherapy to chemotherapy in the treatment of early-stage hormone receptor-positive metaplastic breast cancer and may help inform future directions in managing this rare and understudied subgroup. Citation Format: D. Edwards, C. Coleman, A. Jamil. Early-stage hormone receptor-positive metaplastic breast cancer treated with chemo-immunotherapy: a case report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-03.