Metaplastic breast cancer: Clinical and prognostic features.

Abstract

e13163 Background: Metaplastic breast cancer (MpBC) is a rare, aggressive malignancy characterized by differentiation of neoplastic epithelium into epithelial and mesenchymal elements. MpBC carries a poorer prognosis than invasive ductal carcinoma, likely due to molecular and histological heterogeneity and lack of optimized treatment. The complexity of MpBC necessitates further study into clinical features and potential prognostic markers. Methods: An IRB-approved retrospective chart review was conducted on 186 patients with MpBC and 76 patients with non-metaplastic, triple-negative breast cancer from January 2000 to August 2023. Electronic medical records were used to collect demographics, diagnosis date, pathology, staging, metastases, hormone receptor status, molecular data, and date of death or last follow-up. Overall survival (OS) was the primary outcome. Kaplan-Meier analysis summarized time-to-event variables, with the log-rank test and univariate Cox regression assessing associations between OS and characteristics. Results: MpBC was diagnosed at a median age of 62 years, with most cases at stage 1 or 4. Most patients were White (70%) or Black (26.1%). Metastases occurred in 83.9% of MpBC cases, compared to 61.8% of non-metaplastic cases. Tumors showed predominantly squamous differentiation, followed by spindle and chondroid. Frequent mutations included BRCA, KIT, c-MYC, and p53; PD-L1 expression was detected in 8.1% (n = 15), and triple-negative status in 24% (n = 45) of MpBC cases. Triple-negative status was associated with reduced OS (p = 0.0009) and higher mortality (p = 0.0003) compared to ER, PR, or HER2 expression within the MpBC cohort. The 2-, 5-, and 10-year OS rates for triple-negative MpBC patients were 66% (95% CI: 49–78%), 66% (95% CI: 49–78%), and 57% (95% CI: 33–75%), with a hazard ratio of 3.54 (95% CI: 1.78–7.05). MpBC patients with HER2, ER, or PR expression had 2-, 5-, and 10-year OS rates of 91% (95% CI: 85–95%), 89% (95% CI: 82–93%), and 84% (95% CI: 75–90%). Across both cohorts, PD-L1-negative patients had a 7.4-fold higher mortality risk than PD-L1-positive patients (p = 0.0309). PD-L1-positive patients had an estimated 2-year OS of 84% (95% CI: 58–95%) compared to 33% (95% CI: 1–77%) among PD-L1-negative patients. Conclusions: This study highlights the potential prognostic value of hormone receptor status and PD-L1 expression in metaplastic and non-metaplastic, triple-negative breast cancer. Triple-negative hormone receptor status was linked to decreased overall survival in MpBC patients, while negative PD-L1 expression was tied to increased mortality. Further studies are needed to validate these findings and improve outcomes for this aggressive malignancy.