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. 2014 Feb;132(2):280-6.
doi: 10.1016/j.ygyno.2013.12.009. Epub 2013 Dec 12.

Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations

James R Conner  1 , Emily Meserve  1 , Ellen Pizer  2 , Judy Garber  3 , Michael Roh  4 , Nicole Urban  5 , Charles Drescher  6 , Bradley J Quade  1 , Michael Muto  7 , Brooke E Howitt  1 , Mark D Pearlman  8 , Ross S Berkowitz  7 , Neil Horowitz  7 , Christopher P Crum  9 , Colleen Feltmate  7
Affiliations

Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations

James R Conner et al. Gynecol Oncol. 2014 Feb.

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.

Keywords: BRCA; Fallopian; Ovarian cancer; Serous cancer.

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Conflict of interest statement

Conflicts of Interest

The authors declare there are no conflicts of interest.

Figures

Figure 1
Figure 1. BRCA1 and BRCA2 gene mutation status in the BWH cohort
A total of 385 patients were designated as having a BRCA gene mutation on the pathology requisition submitted at the time of RRSO. Subsequent chart review revealed documented mutations in BRCA1, BRCA2, or both (classified as “other”) in 349, whereas 36 cases were not confirmed. The nature of the mutations (del = known deleterious, UK = exact mutation unknown after chart review, indet = effect of mutation indeterminate) and frequency of neoplasia in each category are shown.
Figure 2
Figure 2. Age distribution of patients undergoing risk-reducing salpingo-oophorectomy and patients with neoplasia
A. Histogram showing ages for all patients undergoing risk-reducing salpingooophorectomy at BWH (grey) and the subset of patients with neoplasia (red). Patients with neoplasia were significantly older than patients without evidence of disease (p=0.0009). B. Age-related risk of unsuspected neoplasia at RRSO. Patients were grouped into 5 year age bins and the proportion of cases positive for neoplasia was plotted against age. Logistic regression analysis demonstrated a significant relationship between age at time of surgery and likelihood of an unsuspected neoplasia (p<0.001).
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References

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