Aim
Breast cancer is the most common cancer among Australian women and despite advances in prevention, early detection, and treatment recurrence rates remain at 25-30%. This systematic literature review summarises the current evidence for ER,PR and HER2 discordance rates between primary and recurrent breast cancer, discordance impact on prognosis and evidence of primary tumour heterogeneity.
Methods
Web of Science, Scopus, MEDLINE and PubMed were searched with keywords ‘Breast Cancer’ AND ‘Primary’ AND ‘Recurrence’ AND ‘Discordance’ AND ‘Heterogen*’ or equivalent for publications from January 2013 to December 2023. The end points of interest were discordance rates, prognosis and evidence of tumour heterogeneity. Only studies with paired histopathology that employed immunohistochemistry were included.
Results
Searches identified 846 publications, of which 10 were eligible. All were retrospective cohort studies, two of which were prospectively planned. Average discordance rates for ER, PR and HER2 were 19.31%, 34.49% and 15.04% respectively. PR discordance was consistently the highest. ER and PR receptor loss were observed more frequently than gain. The opposite was true for HER2. ER and PR receptor loss were associated with a worse prognosis. Primary endocrine adjuvant treatment was associated with ER and PR loss. Receptor gain was associated with a better prognosis following treatment. Both intratumour and intertumour heterogeneity were observed.
Conclusions
We found discordance rates between primary and metastatic sites, suggesting resistant tumour clones and potential for poorer prognosis. Patients losing ER and PR had worse outcomes, while those gaining receptors responded well to treatment changes. We recommend re-biopsy of recurrent breast cancer, if feasible. Despite these insights, more research is needed to fully understand tumour heterogeneity and receptor discordance, which could significantly impact treatment and prognosis.