Receptor discordance in metastatic breast cancer lesions associated with poorer overall survival in a retrospective cohort study

PurposeTo investigate real-world changes in the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and corresponding molecular subtypes in primary and metastatic breast cancer, as well as their influencing factors and impact on prognosis.MethodsThis retrospective study analyzed 436 paired lesion samples of primary and metastatic breast cancer treated between 2013 and 2023. Statistical evaluation was conducted to examine receptor discordance (ER, PR, HER2) and clinicopathological correlations.ResultReceptor discordance rates between primary and metastatic lesions were 25.1% for ER, 33.3% for PR, 32.8% for HER2, and 33.8% for molecular subtypes. PR showed the highest discordance, frequently transitioning from positive to negative. ER discordance predominantly involved the loss of low expression. HER2 discordance was highest in liver metastases (59.3%). Molecular subtype changes were most common in HR+/HER2- tumors (42.6%). ER discordance correlated with neoadjuvant chemotherapy and endocrine therapy, while HER2 discordance was linked to targeted therapy and lung metastases. Loss of hormone receptor (HR) or HER2 expression was associated with poorer overall survival (OS) (HR: median OS 95 vs. 70 months, P = 0.0018; HER2: median OS 78 vs. 68 months, P = 0.025). Conversely, sustained or acquired HR/HER2 positivity improved OS.ConclusionsHeterogeneity in ER, PR, HER2, and molecular subtype expression significantly influences prognosis and treatment outcomes in metastatic breast cancer. Reassessment of receptor status in metastatic lesions is essential for optimizing individualized treatment strategies and improving patient outcomes.