Patterns of care and outcomes of risk reducing surgery in women with pathogenic variants in non-BRCA and Lynch syndrome ovarian cancer susceptibility genes

Gynecol Oncol. 2023 Jun:173:1-7. doi: 10.1016/j.ygyno.2023.03.017. Epub 2023 Apr 6.

Abstract

Objectives: Guidelines recommend risk-reducing bilateral salpingo-oophorectomy (RRSO) for women with pathogenic variants of non-BRCA and Lynch syndrome-associated ovarian cancer susceptibility genes. Optimal timing and findings at the time of RRSO for these women remains unclear. We sought to characterize practice patterns and frequency of occult gynecologic cancers for these women at our two institutions.

Methods: Women with germline ovarian cancer susceptibility gene pathogenic variants who underwent RRSO between 1/2000-9/2019 were reviewed in an IRB-approved study. All patients were asymptomatic with no suspicion for malignancy at time of RRSO. Clinico-pathologic characteristics were extracted from the medical records.

Results: 26 Non-BRCA (9 BRIP1, 9 RAD51C, and 8 RAD51D) and 75 Lynch (36 MLH1, 18 MSH2, 21 MSH6) pathogenic variants carriers were identified. Median age at time of RRSO was 47. There were no occurrences of occult ovarian or fallopian tube cancer in either group. Two patients (3%) in the Lynch group had occult endometrial cancer. Median follow up was 18 and 35 months for non-BRCA and Lynch patients, respectively. No patient developed primary peritoneal cancer upon follow up. Post-surgical complications occurred in 9/101 (9%) of patients. Hormone replacement therapy (HRT) was rarely used despite reported post-menopausal symptoms in 6/25 (23%) and 7/75 (37%) patients, respectively.

Conclusions: No occult ovarian or tubal cancers were observed in either group. No recurrent or primary gynecologic-related cancers occurred upon follow-up. Despite frequent menopausal symptoms, HRT use was rare. Both groups experienced surgical complications when hysterectomy and/or concurrent colon surgery was performed suggesting concurrent surgeries should only be performed when indicated.

Keywords: BRIP1; Lynch; MLH1; MSH2; MSH6; Non-BRCA; RAD51C; RAD51D; Risk-reducing; Salpingo-oophorectomy.

MeSH terms

  • Breast Neoplasms* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / surgery
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Neoplasms, Unknown Primary* / genetics
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Ovarian Neoplasms* / surgery
  • Ovariectomy
  • Risk Factors