CORRESPONDENCE

Re: Gynecologic Surgeries and Risk of Ovarian Cancer in Women with BRCA1 and BRCA2 Ashkenazi Founder Mutations: An Israeli Population-Based Case-Control Study

William D. Foulkes, Steven A. Narod, Kenneth Swenerton, Karen Panabaker, Lucy Gilbert

Affiliations of authors: Program in Cancer Genetics (WDF), Division of Gynecological Oncology, Department of Obstetrics and Gynecology (LG), McGill University, Montreal, Quebec, Canada; Centre for Research in Women's Health, University of Toronto, Ontario, Canada (SAN); Hereditary Cancer Program, British Columbia Cancer Agency, Vancouver, British Columbia, Canada (KS, KP).

Correspondence to: William D. Foulkes, MB, PhD, Montreal General Hospital, Rm. L10-116, 1650 Cedar Ave., Montreal, QC, H3G 1A4, Canada (e-mail: william.foulkes{at}mcgill.ca).

The article by Rutter et al. (1) is an important addition to the literature. It is noteworthy that of the eight cases of presumed papillary serous carcinoma of the peritoneum reported by the authors, five occurred in BRCA1 mutation carriers, two occurred in non-carriers, and one affected woman was not tested. There were no cases of papillary serous carcinoma of the peritoneum reported in the 64 women who were carriers of the BRCA2 6174delT mutation. We report here what we believe to be the first two cases of papillary serous carcinoma of the peritoneum occurring in women carrying BRCA2 mutations who had a total abdominal hysterectomy and bilateral salphingo-oophorectomy (TAH/BSO) before the diagnosis of a pelvic cancer.

The first case patient was a multiparous woman aged 61 years, identified as carrying the Ashkenazi Jewish founder BRCA2 6174delT mutation in March 1997. The patient opted to have a TAH/BSO by a gynecologic oncologist in June 1997. There was no clinical or pathological evidence of malignancy in the abdomen or in the removed tissues. She continued with surveillance for breast cancer, but ceased screening for ovarian cancer. In December 2000, she presented with a 2-week history of colicky pain. Her serum CA 125 level was 1608 U/mL. Subsequent investigation led to a laparotomy, and a stage IIIC, poorly differentiated serous papillary carcinoma was found.

The second case patient was a nulliparous Ashkenazi Jewish woman aged 50 years, identified as carrying the BRCA2 6174delT mutation in March 1998. She underwent a bilateral prophylactic mastectomy 2 months later, followed by a prophylactic TAH/BSO by a gynecologic oncologist in September 1998. The tissues removed were reported as being normal after a pathologic examination. Breast and ovarian cancer screening ceased after these procedures. In April 2001, the patient experienced abdominal bloating and discomfort. Endovaginal ultrasound showed ascites but no masses. Her serum CA 125 level was 5300 U/mL. A diagnosis of grade 3 peritoneal papillary serous carcinoma was made after computed tomography-directed paracentesis and cytologic examination.

As reported by Rutter et al. (1), papillary serous carcinoma of the peritoneum is known to occur in BRCA1 mutation carriers after prophylactic oophorectomy (2-4) but has not been reported in BRCA2 mutation carriers who had a TAH/BSO. The lifetime risk for ovarian cancer in a BRCA2 mutation carrier is approximately 11% and is generally lower than the risk of ovarian cancer in BRCA1 mutation carriers (39%) (5). The risk of papillary serous carcinoma of the peritoneum, either before or after TAH/BSO, in BRCA1/2 mutation carriers is unknown. In some ways, despite the lack of previous reports, our findings are not surprising, because the BRCA2 6174delT mutation is located within a region of the BRCA2 gene that is believed to be associated with a higher risk of ovarian cancer (6). Interestingly, it may be that the known later onset of ovarian cancer in BRCA2 6174delT mutation carriers, compared with the age of onset of ovarian cancer in BRCA1 carriers, has delayed the identification of papillary serous carcinoma of the peritoneum in BRCA2 mutation carriers.

Long-term follow-up of cohorts of women undergoing prophylactic oophorectomy (3) will be required to establish the true incidence of papillary serous carcinoma of the peritoneum in both BRCA1 and BRCA2 mutation carriers, but it is likely to reflect differences observed in ovarian cancer incidence noted above. Annual endovaginal ultrasound and determination of CA 125 levels do not appear to be effective in detecting either ovarian or extra-ovarian papillary serous carcinomas at an early stage. Even increasing the frequency of ultrasound screening cannot eliminate presentation in advanced-stage disease (7). The role of more frequent CA 125 testing to detect early-stage papillary serous carcinoma of the peritoneum, insofar as this entity exists, is unknown.

NOTES

Editor's note: Rutter et al. declined to respond.

REFERENCES

1 Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, et al. Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 2003;95:1072-8.[Abstract/Free Full Text]

2 Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van't Veer L, Garber JE, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 2002;346:1616-22.[Abstract/Free Full Text]

3 Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2002;346:1609-15.[Abstract/Free Full Text]

4 Halperin R, Zehavi S, Langer R, Hadas E, Bukovsky I, Schneider D. Primary peritoneal serous papillary carcinoma: a new epidemiologic trend? A matched-case comparison with ovarian serous papillary cancer. Int J Gynecol Cancer 2001;11:403-8.[CrossRef][ISI][Medline]

5 Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003;72:1117-30.[CrossRef][ISI][Medline]

6 Thompson D, Easton D; Breast Cancer Linkage Consortium. Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 2001;68:410-9.[CrossRef][ISI][Medline]

7 Liede A, Karlan BY, Baldwin RL, Platt LD, Kuperstein G, Narod SA. Cancer incidence in a population of Jewish women at risk of ovarian cancer. J Clin Oncol 2002;20:1570-7.[Abstract/Free Full Text]



             
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