James R Conner1, Emily Meserve1, Ellen Pizer2, Judy Garber3, Michael Roh4, Nicole Urban5, Charles Drescher6, Bradley J Quade1, Michael Muto7, Brooke E Howitt1, Mark D Pearlman8, Ross S Berkowitz7, Neil Horowitz7, Christopher P Crum9, Colleen Feltmate7. 1. Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, USA. 2. Cell-Netix, Seattle, USA. 3. Dana Farber/Brigham and Women's Cancer Center, Boston, MA, USA. 4. Department of Pathology, University of Michigan Medical School, Ann Arbor, USA. 5. Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. University of Washington School of Medicine, Seattle, WA, USA. 7. Division of Gynecologic Pathology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, USA. 8. Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, USA. 9. Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, USA. Electronic address: ccrum@partners.org.
Abstract
OBJECTIVE: This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCA(m+)) and determined recurrence risk. METHODS: We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCA(m+) women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions. RESULTS: Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCA(m+) cohort without neoplasia (47.8) and frequency increased with age (p < 0.001). Twenty-nine BRCA(m+) patients with neoplasia from three institutions were followed for a median of 5 years (1-8 years.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027). CONCLUSIONS: Adnexal neoplasia is present in 5-6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN.
OBJECTIVE: This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCA(m+)) and determined recurrence risk. METHODS: We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCA(m+) women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions. RESULTS: Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCA(m+) cohort without neoplasia (47.8) and frequency increased with age (p < 0.001). Twenty-nine BRCA(m+) patients with neoplasia from three institutions were followed for a median of 5 years (1-8 years.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027). CONCLUSIONS:Adnexal neoplasia is present in 5-6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN.
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