Approximately 90% of breast cancer deaths are due to metastatic dissemination. The most common sites of breast cancer metastasis include the lung, liver and bone, however breast tumours can also spread to the gynaecological organs. Metastasis to gynaecological organs accounts for 7-10% of all gynaecological malignancies and are hard to diagnose, patients can be asymptomatic for many years and present with widespread metastatic disease. In order to understand the molecular phenotype and biological mechanisms of breast tumours that spread to the gynaecological organs, we have begun analyzing clinical details, tumour morphology and immunophenotypic data from 54 breast cancer patients with gynaecological metastases.
The average age of patients at diagnosis of their primary tumour was 49 years (median 47 years, range 30-79), while the average time to metastasis was 6 years (range 0-20 years). Invasive lobular carcinoma accounted for 43% of the primary tumours. Seventy-two percent of patients developed metastasis to additional sites; most commonly, peritoneum/omentum (21.7%) followed by gastrointestinal organs (10.6%). Interestingly, the common sites of breast cancer metastasis were rarely involved: bone (5.5%); lung (1.8%); liver (1.8%); and brain (1.4%). Immunohistochemical staining showed that the primary tumours were largely ER (88.1%), PR (75.9%) and AR (87.5%) positive, HER2 negative (96.4%) and basal marker (CK5/6, EGFR and CK14) negative (100%). ER, PR and HER2 expression remained unchanged during metastatic progression in 79.3%, 59.1% and 91.4% of cases, respectively.
Overall, patients with gynaecological metastasis represent a young patient cohort, often associated with metastasis to other abdominal cavity organs. The primary tumour and metastases are frequently ER and PR positive and lack markers of aggressive phenotypes. The stable expression of ER during progression suggests a potential role for hormone regulation in dissemination to these sites. Further work will help uncover the mechanism of spread to these particular sites.