In an Israeli retrospective cohort study reported as a research letter in JAMA Network Open, Armon et al found that presymptomatic awareness of BRCA1/BRCA2 pathogenic variant carrier status was associated with better outcomes in several measures in women with ovarian cancer.
Study Details
The two-center study involved data on 132 carriers of germline BRCA1/BRCA2 pathogenic variants diagnosed with ovarian cancer between 2000 and 2023. Patients received guideline-based surveillance and prevention recommendations, including risk-reducing bilateral salpingo-oophorectomy (RR-BSO).
Key Findings
Among the 132 patients included in the analysis (mean patient age = 56.9 ± 11.2 years), 34 were aware of their pathogenic variant carrier status prior to cancer diagnosis, and 98 became aware of their status after diagnosis. Patients with prediagnosis awareness had earlier-stage disease at diagnosis vs those with postdiagnosis awareness (eg, stage I in 32.3% vs 6.3%; P = .001).
On multivariate analysis, postdiagnosis awareness was associated with more advanced stage of disease at diagnosis (odds ratio = 4.35, 95% confidence interval [CI] = 1.49–12.72, P = .007). Downstaging in patients with prediagnosis awareness was reflected by lower CA-125 levels (mean = 346 IU vs 1,749 IU, P < .001), fewer ultrasonographic findings at diagnosis (76.2% vs 94.9%, P = .02), more diagnoses through surveillance (20.0% vs 13.6%, P < .001) and RR-BSO (44.0% vs not applicable, P < .001), and lower rates of second-line treatment (53.4% vs 73.5%, P = .01).
Furthermore, prediagnosis awareness was associated with significantly better disease-free survival (hazard ratio = 0.38, 95% CI = 0.18–0.83, P = .02) on multivariate analysis. No difference in overall survival was observed, with 5-year rates being 80% vs 75%. The two groups had similar rates of optimal debulking and recurrence.
The investigators stated: “The findings on BRCA-pathogenic variant carriers diagnosed with [ovarian cancer] reflect older age at genetic testing and RR-BSO deferral. Prediagnosis awareness of BRCA status was associated with earlier stage at diagnosis, fewer second-line treatments, and longer [disease-free survival]. No significant [overall survival] advantage was observed, which could be explained by limited sample size but may be consistent with observations that, in the general population, [ovarian cancer] downstaging does not translate to decreased mortality….”
Shunit Armon, MD, of the Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was supported by the Breast Cancer Research Foundation and Israel Cancer Association. For disclosure information for study authors, visit jamanetwork.com.
