HER2 discordance between primary and metastatic breast cancer: assessing the clinical impact

In the setting of breast cancer relapse, treatment decisions are typically made by utilizing HER2, estrogen, and progesterone receptor expression status of the primary breast cancer. Recently, concern regarding receptor discordance has led to recommendations for rebiopsy for all cases of metastatic disease. However, whether this is an appropriate recommendation is uncertain, particularly as the clinical implications for HER2 discordance are unknown.

We performed a literature review to identify studies assessing HER2 discordance between primary and metastatic breast cancer. These studies were then reviewed for data relating to (1) impact of clinical factors on discordance rates, (2) prognostic impact of discordance, or (3) clinical outcomes from treatment alteration due to receptor discordance. Results were analyzed qualitatively.

From 60 HER2 discordance studies identified, 24 contained information of interest for this review. No clear factor promoting HER2 discordance was identified. Loss of HER2 seemed to result in worse post-relapse survival and overall survival, although these data were often confounded by lack of treatment in the setting of receptor loss. Conversely, HER2 discordance was not associated with shorter DFS. Individual patients with receptor gain appear to have benefited from addition of targeted treatment, although data are limited to case reports.

Evidence of HER2 discordance leading to alterations in patient outcomes is limited, highlighting the need for further research in this area. Furthermore, lack of alteration in patient outcomes suggests that a more pragmatic approach to the decision to rebiopsy may be appropriate.