Clinicopathological, immunohistochemical and treatment features of metachronous versus synchronous bilateral breast carcinoma

Objectives. The purpose of this study was to assess and compare the clinicopathological, molecular pathology, treatment and survival characteristics in patients with metachronous bilateral breast cancer (mBBC) and synchronous breast cancer (sBBC). Materials and methods. A cohort of 658 patients with breast cancer treated at the Coltea Clinical Hospital, Surgery Department, between January 2015 and December 2019 and followed-up until August 2020 was studied. Data pertaining to patients who were diagnosed as having bilateral breast cancer were retrospectively reviewed and collected. A 3-months interval was used to distinguish metachronous from synchronous tumors. Among patients with bilateral breast cancer, assessment parameters included patient characteristics, histological and molecular pathology features and the performed treatment that were statistically evaluated comparing the first and second tumor of each group and among groups. Survival analysis was performed comparing mBBC and sBBC patients. SPSS was used for data analysis. Outcomes. Of the 658 patients with primary breast cancer, 35 (5.3%) patients were diagnosed as having bilateral breast cancer (25 (3.8%) mBBC and 10 (1.5%) sBBC). When clinical and histopathological parameters were statistically evaluated, age, menopausal status, tumor size, number of invaded nodes and anatomic stage were found to be significant between the tumors of the metachronous group and tumor size, pathologic T(tumor) and stage between tumors of the synchronous group. Hormonal receptor (HR) status concordance was higher in the synchronous group (85.7%, p = 0.010), with a higher percentage of ER positive (71.4%) and PR positive (71.4%) concordance of the tumors. In terms of survival analysis, there was a difference in overall survival (OS, p = 0.005), disease-free survival (DFS, p = 0.011) and distant relapse-free survival (p = 0.003) between mBBC and sBBC. The mean disease-free survival for patients in whom metachronous tumor occurred within less than 5 years was 63.3 months, for sBBC patients was 39.6 months, whereas for patients with more than 5 years was 437.9 months (p = 0.012, Log Rank). Discordant biomarker defined subgroup (ER,HER2) patients were associated with better disease-free survival (p = 0.047, Log Rank) and better distant relapse-free survival (p = 0.015, Log Rank) in overall patients. In terms of loco-regional relapse-free survival, although mBBC and sBBC patients showed no statistical significant difference earlier in the time course (p = 0.088, Breslow; p = 0.054 Tarone-Ware), among mBBC patients was observed a better outcome (p = 0.027, Log Rank). Conclusions. Based on survival analysis, patients in whom metachronous tumor developed after more than 5 years, had a better distant relapse-free survival. Patients with synchronous bilateral breast cancer were associated with worse disease outcome based on overall survival analysis and disease free-survival rates with more frequent rates of distant metastasis. Outcome of patients in whom metachronous tumor was diagnosed within less than 5 years might be similar to synchronous tumors. Patients with discordant ER,HER2 status showed a better disease outcome. Although concordance in HR status and molecular subtype, did not show statistical significant differences, it is a subject which deserves further clinical observation.