The Discordance Pattern of Molecular Sub-Types Between Primary and Metastatic Sites in Chinese Breast Cancer Patients

Objective: Based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2), and proliferation cell nuclear antigen (Ki-67) status, breast cancer (BC) can be divided into several molecular sub-types. The patterns of these biological receptors may change during the course of progression and metastasis which could lead to new treatment strategies accordingly. Method: The present multi-center-based clinical data investigated the discordance patterns of molecular features in Chinese BC patients between primary tumors and distant metastasis. 151 pathologically confirmed BC patients were enrolled. The comparison of the statuses of ER, PR, HER-2, and the Ki-67 index by the IHC and/or FISH method was performed. Results: The discordance rate in one or more molecular markers was 52.4% and varied between primary and metastatic lesions. The most common transformation pattern was the loss of ER and PR. On the other hand, the ER-positive patients have the longest OS. Patients with ER changing from positive to negative have the shortest OS. The patients with PR changing from negative to positive have the longest OS, while PR-negative patients have the shortest OS. The median DFI (disease-free interval) was 54.93 months in this study. ER, PR, and HER-2 transformation rates are common in patients with DFI < 2 years than in patients with DFI ≥ 5 years. For patients with an ER-positive expression in metastatic lesions, a significantly prolonged PFS was observed (P < 0.05) in those receiving endocrine treatment. Conclusion: The transformation of molecular subtyping status was identified between primary and corresponding relapse lesions and was used for determining the treatment strategies and prognosis prediction in advanced BC patients.