In a study reported in the Journal of Clinical Oncology, Matteo Lambertini, MD, and colleagues identified clinical characteristics of breast cancer in young women carrying germline pathogenic variants in BRCA1 vs BRCA2 and examined the effect of prediagnostic BRCA testing on outcomes.
Matteo Lambertini, MD
Study Details
This study involved data from 4,752 patients with pathogenic variants in BRCA1 or BRCA2 diagnosed with stage I to III invasive breast cancer at age 40 or younger between January 2000 and December 2020 at 78 centers worldwide.
Key Findings
Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) were more likely to have hormone receptor–negative disease (74.4% vs 15.5%) and high-grade tumors (77.5% vs 49.1%).
At a median follow-up of 7.8 years, second primary breast cancers (2.12 vs 1.42 events per 100 person-years) and nonbreast primary malignancies (0.70 vs 0.45 events per 100 person-years) were more frequent among BRCA1 vs BRCA2 carriers, whereas distant recurrences were less frequent (1.51 vs 2.06 events per 100 person-years). The disease-free survival rate at 8 years was 63.8% among BRCA1 carriers and 66.2% among BRCA2 carriers.
Compared with patients tested for BRCA at diagnosis (between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1 = 61.3% vs 32.4%), less nodal involvement (N0 = 65.9% vs 50.8%), reduced receipt of chemotherapy (84.4% vs 92.9%), and reduced receipt of axillary dissection (37.5% vs 47.4%).
Patients tested before diagnosis had better overall survival in unadjusted analysis (hazard ratio [HR] = 0.61, 95% confidence interval [CI] = 0.40–0.92). Significance of the benefit was not maintained after adjustment for potential confounders including tumor stage (HR = 0.74, 95% CI = 0.47–1.15).
The investigators concluded: “This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA pathogenic variant in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted [overall survival].”
Dr. Lambertini, of the Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Italy, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Italian Association for Cancer Research and others. For full disclosures of the study authors, visit ascopubs.org.
