Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers
Related Experiment Video
Updated: Dec 25, 2025
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Semir Vranic1, Phillip Stafford2, Juan Palazzo3
1College of Medicine, QU Health, Qatar University, Doha, Qatar.
Introduction:
Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome.
Materials And Methods:
Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing.
Results:
The majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre- and post-chemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases).
Conclusions:
Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease.
Insights
Spindle cell carcinoma, a rare triple-negative breast cancer, often resists chemotherapy. This study found targetable molecular alterations in most cases, highlighting the need for personalized biomarker profiling for improved treatment outcomes.
Area of Science:
- Oncology
- Genomics
- Breast Cancer Research
Background:
- Spindle cell carcinoma (SCC) is a rare metaplastic breast cancer subtype.
- SCC exhibits a triple-negative phenotype (estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative).
- This subtype is linked to chemotherapy resistance and poor prognosis.
Purpose of the Study:
- To comprehensively analyze biomarkers for immuno-oncology and targeted therapies in pure SCC.
- To identify actionable molecular alterations in SCC for potential therapeutic strategies.
Main Methods:
- Immunohistochemistry and DNA/RNA sequencing were employed.
- Twenty-three pure SCC cases (18 primary, 5 recurrent/metastatic) were analyzed.
- Biomarker profiling included gene mutations, amplifications, and programmed death-ligand 1 expression.
Main Results:
- The majority of SCCs (21/23) were triple-negative.
- Pathogenic mutations (e.g., PIK3CA, TP53, HRAS) were found in 21/23 cases.
- Low tumor mutational burden and microsatellite stability were consistent findings; PD-L1 expression was detected in a subset of tumors.
Conclusions:
- Most SCCs harbor targetable molecular alterations, necessitating individual patient profiling.
- Identifying specific biomarker combinations can enhance treatment strategies for this aggressive breast cancer subtype.
