A study of clinical and molecular characteristics in bilateral primary breast cancer

Abstract

Background: Bilateral primary breast cancer (BPBC) is a rare type of breast cancer. Studies on the clinicopathologic and molecular characteristics of BPBC in a metastatic context are very limited.

Methods: A total of 574 unselected metastatic breast cancer patients with clinical information were enrolled in our next-generation sequencing (NGS) database. Patients with BPBC from our NGS database were regarded as the study cohort. In addition, 1467 patients with BPBC and 2874 patients with unilateral breast cancer (UBC) from the Surveillance, Epidemiology, and End Results (SEER) public database were also analyzed to determine the characteristics of BPBC.

Results: Among the 574 patients enrolled in our NGS database, 20 (3.5%) patients had bilateral disease, comprising 15 (75%) patients with synchronous bilateral disease and 5 (25%) patients with metachronous bilateral disease. Eight patients had bilateral hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) tumors, and three had unilateral HR+/HER2- tumors. More HR+/HER2- tumors and lobular components were found in BPBC patients than in UBC patients. The molecular subtype of the metastatic lesions in three patients was inconsistent with either side of the primary lesions, which suggested the importance of rebiopsy. Strong correlations in clinicopathologic features between the left and right tumors in BPBC were exhibited in the SEER database. In our NGS database, only one BPBC patient was found with a pathogenic germline mutation in BRCA2. The top mutated somatic genes in BPBC patients were similar to those in UBC patients, including TP53 (58.8% in BPBC and 60.6% in UBC) and PI3KCA (47.1% in BPBC and 35.9% in UBC).

Conclusions: Our study suggested that BPBC may tend to be lobular carcinoma and have the HR+/HER2- subtype. Although our study did not find specific germline and somatic mutations in BPBC, more research is needed for verification.

Keywords: bilateral primary breast cancer; clinicopathologic characteristics; mutation landscape; next-generation sequencing.

FIGURE 1

Mutations profiles of bilateral primary breast cancer (BPBC) patients in Fudan University Shanghai Cancer Center. (A) The distribution of the somatic mutations in plasma samples of BPBC patients. (B) The distribution of the somatic mutations in tissue samples of BPBC patients. (C) TMB among different subgroups in our next‐generation sequencing database. PLA, plasma samples; FFP + TIS, tissue samples.

FIGURE 2

Clinicopathologic characteristics of bilateral primary breast cancer (BPBC) patients and unilateral breast cancer (UBC) patients from SEER. (A) Molecular subtype of left and right tumors of BPBC patients in SEER. (B) Histopathology of BPBC patients and UBC patients in SEER. (C) Age of BPBC patients and UBC patients in SEER. Lobular, with lobular component; No lobular, without lobular component; NA, unknown. * 0.01 ≤ p‐value <0.05, ** 0.001 ≤ p‐value <0.01, **** p‐value <0.0001.

FIGURE 3

Comparison of prognosis between bilateral primary breast cancer and unilateral breast cancer. (A) Kaplan–Meier curves of OS in Fudan University Shanghai Cancer Center patients. (B) Kaplan–Meier curves of OS in SEER patients. MST, median survival time.