Background: Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathologic and molecular features of these metastases to better understand this unique pattern of dissemination.
Methods: Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy number profiling and targeted sequencing of 386 cancer-related genes.
Results: The median age of primary tumour diagnosis amongst gynae-metastatic patients was significantly younger compared to a general breast cancer population (46.5 vs.60 years; p<0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8 years (range 0 – 20 years) and survival following a metastatic diagnosis was 1.95 years (range 0 – 18 years). Patients had an average of 5 involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver or brain. Invasive lobular histology and luminal A-like phenotype were over-represented in this group (42.8%, 87.5% respectively) and most patients had involved axillary lymph nodes (p<0.001). Primary tumours frequently co-expressed ER cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24 and 11q13. In terms of phenotype conversion, ER status was generally maintained in metastases, FOXA1 increased, and expression of PR, AR and GATA3 decreased. ESR1 and novel AR mutations were identified.
Conclusion: Metastasis to gynaecological organs is a complication frequently affecting young women with ILC and luminal A-like breast cancer, and hence may be driven by hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.