Prevalence, prognosis, and health care resource utilization in carriers of pathogenic germline variants in BRCA1/2 with incident early-stage breast cancer: a Finnish population-based study

Abstract

Background and purpose: Data on real-world prevalence and outcomes in patients diagnosed with pathogenic germline variants in BRCA1 or BRCA2 (gBRCAm) breast cancer is sparse.

Material and methods: An observational cohort study including all patients diagnosed with incident early-stage breast cancer and recorded in Helsinki University Hospital data lake 2012-2022, accounting for one-third of the Finnish breast cancer patient population.

Results: Among 14,696 incident early-stage breast cancer patients, 11.2% (n = 1,644) were tested for gBRCAm. Of the tested population, 7.4% (n = 122) carried gBRCAm. Of the 122 gBRCAm patients, 95.1% (n = 116) were women, with a median age at diagnosis of 46.4 years. Among the same patient group, HER2 status was available for 87.7% (n = 107) of the patients. Among these, 49.5% (n = 53) had hormone receptor-positive (HR+), HER2-negative breast cancer, 13.1% were (n = 14) HER2-positive, and 37.3% (n = 40) of patients had triple-negative breast cancer. The tested patients were significantly younger compared with non-tested patients. No significant differences in overall survival or healthcare resource utilization between the tested patients with gBRCAm and gBRCA wild-type (gBRCAwt) were observed.

Interpretation: This comprehensive observational study supports previous findings of gBRCAm prevalence in the Western early-stage breast cancer population. While no differences in survival were observed between patients with gBRCAm and gBRCAwt, it is important to consider the potential influence of selection bias, particularly due to the younger gBRCAm testing target population and the overall low frequency of testing. Therefore, a substantial proportion of the patients carrying gBRCAm likely remained undiagnosed, and wider screening criteria are warranted.

Figure 1

Flowchart of the tested and non-tested patients with early-stage breast cancer.

Figure 2

(A) Overall survival (OS), (B) distant disease-free survival (DDFS) in all pathogenic germline BRCA1/2 mutation (gBRCAm) tested patients according to the gBRCAm status (pathogenic or non-gBRCAm/negative for gBRCA1/2 mutation), and (C) invasive disease-free survival (IDFS) in patients with gBRCAm and early-stage breast cancer.

Figure 3

Multivariable Cox model for overall survival (OS) among patients with pathogenic germline BRCA1/2 mutation (gBRCAm) and early-stage breast cancer during the study period.

Figure 4

Healthcare resource utilization (HCRU) and related costs among patients with pathogenic gBRCA1/2 mutation (gBRCAm) overall, according to the biological subtype of breast cancer and among the patients without pathogenic gBRCAm.