Occult serous tubal intraepithelial carcinoma and high-grade serous carcinoma at risk-reducing salpingo-oophorectomy in BRCA1/2 carriers: A Czech two-center cohort.

BACKGROUND

Risk-reducing salpingo-oophorectomy is the standard intervention for prevention of tubo-ovarian carcinoma in women with pathogenic BRCA1/2 variants, yet the optimal timing remains clinically challenging, particularly for BRCA2 carriers.

METHODS

We retrospectively analyzed 329 clinically asymptomatic BRCA1/2 carriers who underwent prophylactic gynecologic surgery with sectioning and extensively examining the fimbria (SEE-FIM) protocol histopathologic assessment at two Czech tertiary centers between November 2014 and September 2024. The primary outcome was occult malignant or premalignant pathology, defined as serous tubal intraepithelial carcinoma (STIC) or invasive high-grade serous carcinoma (HGSC). The cohort included 211 BRCA1 and 118 BRCA2 carriers.

RESULTS

Overall, 10 occult lesions were detected (3.0%, 95% confidence interval 1.7-5.5): five STIC lesions (1.5%) and five occult HGSCs (1.5%). Among BRCA1 carriers, eight lesions were identified (3.8%), including all five STIC lesions and three HGSCs. Among BRCA2 carriers, two occult HGSCs were detected (1.7%), both after the age of 55 years, and no STIC was found. The difference in any occult lesion between BRCA1 and BRCA2 carriers was not statistically significant (p = 0.504), but lesion numbers were small. Occult HGSC occurred at an older age than did STIC (median 55.0 vs. 43.0 years; p = 0.012). In exploratory analyses, a family history of breast cancer and ever smoking were associated with occult lesions, including in a reduced multivariable model, but these findings require cautious interpretation because of the sparse number of events.

CONCLUSIONS

These data support meticulous pathologic evaluation and individualized counseling. The absence of early BRCA2-associated occult lesions should be considered hypothesis generating and should not be interpreted as evidence for delaying risk-reducing salpingo-oophorectomy beyond current recommendations.