Would you continue her 2 neu directed therapy for a patient with breast cancer if a biopsy on progression confirms Her 2 neu negative disease?

There is no good evidence-based answer to this question even though biomarkers (ER, PR, HER2) can change over time (eg. from primary to metastatic recurrence, or pre and post neoadjuvant therapy) in 5-30% of cases.¹ There are no large series assessing outcomes based on changing or not changing therapy on the basis of biomarkers. I typically will use the most recent biopsy to guide management in the case of recurrent disease, with the caveat that suboptimal sampling or processing might negate the findings. However, there is also evidence at the genomic level, there may be branching of genotype/phenotype in different sites due to selective pressures and random effects and this may explain the well-appreciated phenomenon of mixed responses to ...