20 On the Upswing: A Retrospective Cohort Study Evaluating Neoadjuvant Chemotherapy Response in Metaplastic Breast Cancer Patients

Background

Metaplastic carcinoma (Mp) is estimated to account for < 1% of breast cancer diagnoses and is associated with poor outcomes due to chemoresistance. Most are phenotypically high-grade and triple negative, accounting for their aggressive clinical behavior. Studies examining pathologic complete response (pCR) rates with neoadjuvant chemotherapy for Mp breast cancer have varied, ranging from 2% to 23%. With the advent of immune checkpoint inhibitors, like pembrolizumab, which targets PD-L1, pCR has risen meaningfully in early-stage triple-negative breast cancer. We examined our institution’s experience in treating Mp breast cancer and rate of pCR with and without pembrolizumab in the neoadjuvant setting.

Methods

This is a retrospective cohort study of patients with Mp breast cancer who were diagnosed and treated between 2014 and 2024. Patients were identified from the hospital tumor registry. Patient demographics, tumor characteristics, treatment information, and long-term outcomes were collected. We compared tumor characteristics in those who did and did not undergo neoadjuvant chemotherapy and response rates with and without the addition of immunotherapy.

Results

Forty-eight women were included. Three were excluded due to transfer of care (n = 45). Mean age at diagnosis was 58 years (range, 30-84). Most tumors were unifocal (83%), clinical T1 to T2 in size (78%), clinical N0 (74%), and grade 3 (76%). Most were estrogen receptor– (ER) negative, progesterone receptor– (PR) negative, and HER2-negative (83%). Genetic testing was performed in 67%; 2 had BRCA1 pathogenic mutations (6.4%). Twenty-one patients underwent neoadjuvant chemotherapy, and of those, 10 (48%) achieved pCR, 3 of which received pembrolizumab as part of their treatment regimen. All who achieved pCR were alive with no evidence of disease at the time of data collection. Residual tumor cellularity in those who received neoadjuvant chemotherapy ranged from 0% to 90%, with an average of 12%.

Conclusions

A 48% pCR suggests metaplastic breast cancers may be more responsive to modern chemotherapy regimens than previously thought, regardless of germline genetic mutation. Further research in a national database may delineate Mp breast cancer subtypes for which pCR is more likely.