Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast

Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms comprising 0.3-1.0% of all primary breast tumours. The majority of PTs are benign and generally well managed with surgery. However, malignant PTs, and occasionally borderline PTs, can behave in a clinically aggressive manner by metastasizing to distant organs. Although distant metastasis is rare, the prognosis of patients with metastasis is dismal as many are unresponsive to standard chemotherapy and the risk of death is high. In this study, we correlated clinicopathological parameters to survival outcomes in a cohort of patients diagnosed with malignant PTs in our institution. The study cohort comprised 83 cases of malignant PTs diagnosed at the Department of Anatomical Pathology, Singapore General Hospital from 1994 to 2015. Clinicopathological features and follow-up were obtained from hospital records. Metastasis-free survival (MFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared between groups using the log-rank test. Cox regression was carried out to identify factors predictive for metastasis. Mean and median age of patients was 48 years (range 21-71 years). Tumour size measured from 30 to 220 mm (mean 90 mm, median 77 mm). Follow-up data was available for 68 patients. Mean and median follow-up was 90 and 57 months, respectively, with a maximum of 291 months. Distant metastasis occurred in 16 out of 68 patients (23.5%). The most common site of metastasis was the lung. Malignant heterologous elements were observed in 16 (19.3%) cases. Individual clinicopathological parameters had no impact on outcome. On Kaplan-Meier analysis, women with large tumours and presence of malignant heterologous elements showed trends for poorer MFS (p = 0.217 and p = 0.566, respectively). However, the combination of large tumours (≥ 90 mm) containing malignant heterologous elements disclosed significantly worse MFS (p = 0.043) and a trend for poorer OS (p = 0.238). On multivariate analysis, large tumours harbouring malignant heterologous elements independently predicted metastasis (95% CI 1.041-12.517, HR 2.434, p = 0.049). Our study demonstrates that tumour size and presence of malignant heterologous elements predicted metastasis in malignant PTs. Further work needs to be done in determining if protein biomarkers and genomic aberrations are able to additionally refine metastatic risk and define therapeutic targets.