简介：AbstractBackground:Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions.Methods:We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’ demographic profiles and disease characteristics.Results:In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions:The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.