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Pathologic findings and clinical outcomes in women undergoing risk-reducing surgery to prevent ovarian and fallopian tube carcinoma: A large prospective single institution experience

  • Author Footnotes
    1 Present address: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, UW Health Hospital & Clinics, University of Wisconsin – Madison.
    Shannon K. Rush
    Footnotes
    1 Present address: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, UW Health Hospital & Clinics, University of Wisconsin – Madison.
    Affiliations
    Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
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  • Elizabeth M. Swisher
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
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  • Rochelle L. Garcia
    Affiliations
    Department of Pathology, University of Washington Medical Center, United States of America
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  • Kathryn P. Pennington
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
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  • Kathy J. Agnew
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
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  • Mark R. Kilgore
    Affiliations
    Department of Pathology, University of Washington Medical Center, United States of America
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  • Barbara M. Norquist
    Correspondence
    Corresponding author at: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, 1959 NE Pacific Street, Box 356460, Seattle, WA 98195, United States of America.
    Affiliations
    Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Washington Medical Center, United States of America
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  • Author Footnotes
    1 Present address: Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, UW Health Hospital & Clinics, University of Wisconsin – Madison.

      Highlights

      • BRCA1 mutation carriers had the highest frequency of occult neoplasia at time of risk-reducing salpingo-oophorectomy (7.2%).
      • The frequency of occult neoplasia was higher in older BRCA1 and BRCA2 mutation carriers.
      • Nearly 60% of BRCA1 and BRCA2 mutation carriers had risk-reducing surgery after guideline-recommended ages.
      • A PALB2 mutation carrier had an occult fallopian tube neoplasm, highlighting need for serial sectioning for all at risk.

      Abstract

      Objectives

      Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of ovarian, fallopian tube (FT), and peritoneal carcinoma (collectively OC). We describe rates of occult neoplasia in the largest single-institution prospective cohort of women undergoing RRSO, including those with mutations in non-BRCA homologous repair (HRR) genes.

      Methods

      Participants undergoing RRSO enrolled in a prospective tissue bank between 1999 and 2017. Ovaries and FTs were serially sectioned in all cases. Participants had OC susceptibility gene mutations or a family history suggesting OC risk. Analyses were completed in Stata IC 15.1.

      Results

      Of 644 women, 194 (30.1%) had mutations in BRCA1, 177 (27.5%) BRCA2, 27 (4.2%) other HRR genes, and 15 (2.3%) Lynch Syndrome-associated genes. Seventeen (2.6%) had occult neoplasms at RRSO, 15/17 (88.2%) in the FT. Of BRCA1 carriers, 14/194 (7.2%) had occult neoplasia, 8/194 (4.1%) invasive. One PALB2 and two BRCA2 carriers had intraepithelial FT neoplasms. Occult neoplasm occurred more frequently in BRCA1/2 carriers ≥45 years of age (6.5% vs 2.2%, chi square, p = .04), and 211/371 (56.9%) BRCA1/2 carriers had surgery after guideline-recommended ages. Four in 8 (50%) invasive and 2/9 (22%) intraepithelial neoplasms had positive pelvic washings. None with intraepithelial neoplasms developed recurrence or peritoneal carcinoma.

      Conclusions

      BRCA1 carriers have the highest risk of occult neoplasia at RRSO, and the frequency increased with age. Women with BRCA1/2 mutations often have RRSO beyond recommended ages. One PALB2 carrier had FT intraepithelial neoplasia, a novel finding. Serial sectioning is critical to identifying occult neoplasia and should be performed for all risk-reducing surgeries.

      Keywords

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