Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution

Abstract

Background Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast–ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast–ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. Methods To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. Results The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38–58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. Conclusions Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

“…Serous tubal intraepithelial carcinoma (STIC), characterized by non-ciliated tubal epithelial cells that show marked nuclear atypia, mitotic figures, apoptotic bodies, loss of cellular polarization, abnormal p53 staining (a pattern compatible with either missense or deletion mutations), and an increased Ki-67 labeling index, has been recognized as a precancerous lesion of HGSC [ 2 ]. It is often found in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in hereditary breast and ovarian cancer (HBOC) patients with pathogenic variants of BRCA1 and BRCA2 and also found in fallopian tube tissue from patients with HGSC [ 3 4 5 6 ]. The coincidental finding of the TP53 mutation in both HGSC and STIC has led to the recognition of STIC as an early lesion and the TP53 mutation as an early driver mutation of HGSC [ 1 7 8 9 10 11 ].The similarity in morphology, immunophenotype, and gene expression patterns between fallopian tube epithelium and HGSC provides additional evidence that HGSC develops from the fallopian tube [ 12 ].…”