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Baseline and post prophylactic tubal–ovarian surgery CA125 levels in BRCA1 and BRCA2 mutation carriers

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Abstract

The aim of this study was to determine whether BRCA1 and BRCA2 mutation carriers have different baseline CA125 levels compared with non-carriers, and whether a significant difference in pre- and post-operative CA125 levels exists in BRCA mutation carriers undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO). The study also considered whether CA125 measurements should continue in unaffected BRCA mutation carriers after RRBSO. 383 Eligible women were identified through retrospective review of the BRCA Carrier Clinic at The Royal Marsden NHS Foundation Trust, London, UK. These women all had CA125 levels measured as they were either a carrier or at risk of a BRCA1 or BRCA2 mutation. Of these, 76 went on to have a negative predictive test for their familial mutation and so are classed as ‘non-carriers’. 133 BRCA1 and 87 BRCA2 carriers had RRBSO, with a further 26 BRCA1 carriers, 28 BRCA2 carriers and one non-carrier developing ovarian cancer. The remaining 21 BRCA1 and 28 BRCA2 carriers did not have RRBSO or develop ovarian cancer in the time of study follow-up. CA125 levels were measured as surveillance or as part of pre-RRBSO care. CA125 measurement post-RRBSO was continued in 48 BRCA1 and 40 BRCA2 carriers. In 154 BRCA1 mutation carriers, the median baseline (i.e. before RRBSO and with no clinical signs of ovarian cancer) CA125 level was 9.0 U/ml (range 2–78) and was 10.0 U/ml (range 1–43) in 115 BRCA2 mutation carriers. When compared with the 75 non-carriers (median baseline CA125 10.0 U/ml; range 2–52), there was no significant difference between the BRCA1, BRCA2 and non-carrier groups. There was a significant reduction in CA125 from pre- to post-RRBSO in 48 BRCA1 carriers (p = 0.04) but no significant difference in 40 BRCA2 mutation carriers (p = 0.5). Out of a total of 220 mutation carriers who underwent RRBSO, two had an incidental ovarian cancer found on histopathology and another developed primary peritoneal cancer during the follow-up period. Our study is the first to compare initial serum CA125 levels in BRCA1 and BRCA2 mutation carriers with those of non-carriers. Our study found no significant difference between the three groups. A drop in CA125 levels after RRBSO in BRCA1 carriers supports the finding of earlier studies, but differed in that the fall was not seen in BRCA2 carriers. The finding of only one case of post-operative peritoneal cancer in 220 carriers undergoing RRBSO supports the discontinuation of post-RRBSO serum CA125 monitoring in BRCA mutation carriers.

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References

  1. Jacobs IJ, Menon U (2004) Progress and challenges in screening for early detection of ovarian cancer. Mol Cell Proteomics 3(4):355–366

    Article  CAS  PubMed  Google Scholar 

  2. Alsop K, Fereday S, Meldrum C, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C, Friedlander M (2012) BRCA mutation frequency and patterns of treatment response in BRCA mutation–positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol 30(21):2654–2663

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Zhang S, Royer R, Li S, McLaughlin JR, Rosen B, Risch HA, Fan I, Bradley L, Shaw PA, Narod SA (2011) Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer. Gynecol Oncol 121(2):353–357

    Article  CAS  PubMed  Google Scholar 

  4. King M-C, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646

    Article  CAS  PubMed  Google Scholar 

  5. Antoniou A, Pharoah P, Narod S, Risch HA, Eyfjord JE, Hopper J, Loman N, Olsson H, Johannsson O, Borg Å (2003) 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 Human Genet 72(5):1117–1130

    Article  CAS  Google Scholar 

  6. Evans DG, Gaarenstroom KN, Stirling D, Shenton A, Maehle L, Dørum A, Steel M, Lalloo F, Apold J, Porteous M (2009) Screening for familial ovarian cancer: poor survival of BRCA1/2 related cancers. J Med Genet 46(9):593–597

    Article  CAS  PubMed  Google Scholar 

  7. Oei A, Massuger L, Bulten J, Ligtenberg M, Hoogerbrugge N, De Hullu J (2006) Surveillance of women at high risk for hereditary ovarian cancer is inefficient. Br J Cancer 94(6):814–819

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Rosenthal AN, Fraser L, Manchanda R, Badman P, Philpott S, Mozersky J, Hadwin R, Cafferty FH, Benjamin E, Singh N, Evans DG, Eccles DM, Skates SJ, Mackay J, Menon U, Jacobs IJ (2013) Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol Off J Am Soc Clin Oncol 31(1):49–57

    Article  Google Scholar 

  9. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. J Am Med Assoc 304(9):967–975

    Google Scholar 

  10. Domchek SM, Weber B (2006) Clinical management of BRCA1 and BRCA2 mutation carriers. Oncogene 25(43):5825–5831

    Article  CAS  PubMed  Google Scholar 

  11. Bast RC Jr, Feeney M, Lazarus H, Nadler L, Colvin R, Knapp R (1981) Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Investig 68(5):1331

    Article  PubMed Central  PubMed  Google Scholar 

  12. Høgdall E (2008) Cancer antigen 125 and prognosis. Curr Opin Obstet Gynecol 20(1):4–8

    Article  PubMed  Google Scholar 

  13. Kobayashi H, Ooi H, Yamada Y, Sakata M, Kawaguchi R, Kanayama S, Sumimoto K, Terao T (2007) Serum CA125 level before the development of ovarian cancer. Int J Gynecol Obstet 99(2):95–99

    Article  CAS  Google Scholar 

  14. Bast RC Jr, Klug TL, John ES, Jenison E, Niloff JM, Lazarus H, Berkowitz RS, Leavitt T, Griffiths CT, Parker L (1983) A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. New Engl J Med 309(15):883–887

    Article  PubMed  Google Scholar 

  15. Granberg S, Wikland M, Friberg L-G (1990) Tumor marker CA 125 level and ovarian volume at different cycle day periods and in postmenopause. Int J Gynecol Obstet 33(2):149–152

    Article  CAS  Google Scholar 

  16. Zurawski VR, Sjovall K, Schoenfeld DA, Broderick SF, Hall P, Bast RC, Eklund G, Mattsson B, Connor RJ, Prorok PC (1990) Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer. Gynecol Oncol 36(3):299–305

    Article  PubMed  Google Scholar 

  17. van Altena AM, Holtsema H, Hendriks JC, Massuger LF, de Hullu JA (2011) Cancer antigen 125 level after a bilateral salpingo-oophorectomy: what is the contribution of the ovary to the cancer antigen 125 level? Menopause 18(2):133–137

    PubMed  Google Scholar 

  18. Benedet J, Bender H, Jones H III, Ngan H, Pecorelli S (2000) FIGO Committee on gynecologic oncology. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. Int J Gynecol Obstet 70:209–262

    Article  CAS  Google Scholar 

  19. Kabawat S, Bast R Jr, Bhan A, Welch WR, Knapp R, Colvin R (1983) Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125. Int J Gynecol Pathol 2(3):275–285

    Article  CAS  PubMed  Google Scholar 

  20. Alagoz T, Buller RE, Berman M, Anderson B, Manetta A, DiSaia P (1994) What is a normal CA 125 level? Obstet Gynecol Surv 49(11):764–765

    Article  Google Scholar 

  21. Wilder JL, Pavlik E, Straughn JM, Kirby T, Higgins RV, DePriest PD, Ueland FR, Kryscio RJ, Whitley RJ, Nagell JV (2003) Clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation. Gynecol Oncol 89(2):233–235

    Article  CAS  PubMed  Google Scholar 

  22. Bosse K, Rhiem K, Wappenschmidt B, Hellmich M, Madeja M, Ortmann M, Mallmann P, Schmutzler R (2006) Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study. Gynecol Oncol 103(3):1077–1082

    Article  CAS  PubMed  Google Scholar 

  23. Kurihara T, Mizunuma H, Obara M, Andoh K, Ibuki Y, Nishimura T (1998) Determination of a normal level of serum CA125 in postmenopausal women as a tool for preoperative evaluation and postoperative surveillance of endometrial carcinoma. Gynecol Oncol 69(3):192–196

    Article  CAS  PubMed  Google Scholar 

  24. Vasen H, Tesfay E, Boonstra H, Mourits M, Rutgers E, Verheyen R, Oosterwijk J, Beex L (2005) Early detection of breast and ovarian cancer in families with BRCA mutations. Eur J Cancer 41(4):549–554

    Article  CAS  PubMed  Google Scholar 

  25. Eisen A, Weber BL (1998) Primary peritoneal carcinoma can have multifocal origins: implications for prophylactic oophorectomy. J Natl Cancer Inst 90(11):797–798

    Article  CAS  PubMed  Google Scholar 

  26. Tobacman J, Tucker M, Kase R, Greene M, Costa J, Fraumeni JRJ (1982) Intra-abdominal carcinomatosis after prophylactic oophorectomy in ovarian-cancer-prone families. Lancet 320(8302):795–797

    Article  Google Scholar 

  27. Piver MS, Jishi MF, Tsukada Y, Nava G (1993) Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. A report of the Gilda Radner Familial Ovarian Cancer Registry. Cancer 71(9):2751–2755

    Article  CAS  PubMed  Google Scholar 

  28. Thompson D, Easton DF (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94(18):1358–1365

    Article  CAS  PubMed  Google Scholar 

  29. Levine DA, Argenta PA, Yee CJ, Marshall DS, Olvera N, Bogomolniy F, Rahaman JA, Robson ME, Offit K, Barakat RR (2003) Fallopian tube and primary peritoneal carcinomas associated with BRCA mutations. J Clin Oncol 21(22):4222–4227

    Article  CAS  PubMed  Google Scholar 

  30. Olivier R, Van Beurden M, Lubsen M, Rookus M, Mooij T, Van de Vijver M, Van’t Veer L (2004) Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up. Br J Cancer 90(8):1492–1497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade O, McLennan J, Karlan B, Weitzel J, Sun P, Narod S (2006) Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. J Am Med Assoc 296(2):185–192

    Google Scholar 

  32. Gotlieb W, Barchana M, Ben-Baruch G, Friedman E (2006) Malignancies following bilateral salpingo-oophorectomy (BSO). Eur J Surg Oncol 32(10):1231–1234

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge support from Cancer Research UK Grant C5047/A7357 and are grateful for the support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.

Conflict of interest

RE has received educational grant support from Vista Diagnostics, GenProbe (formerly Tepnel), Illumina and Janssen-Cilag.

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Correspondence to Rosalind Eeles.

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The Carrier Clinic Collaborators: Royal Marsden NHS Foundation Trust, London: Imogen Locke, Julian Barwell, Lisa Walker, Gillian Mitchell, Anita Mitra, Sameer Jhavar, Susan Shanley; The Institute of Cancer Research, London: Fiona Lennard, Zsofia Kote-Jarai, Richard Houlston, Nazneen Rahman; Kennedy Galton Centre, London: Huw Dorkins, Carole Cummings; Addenbrooke’s Hospital, Cambridge: Joan Paterson.

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Chen, Y., Bancroft, E., Ashley, S. et al. Baseline and post prophylactic tubal–ovarian surgery CA125 levels in BRCA1 and BRCA2 mutation carriers. Familial Cancer 13, 197–203 (2014). https://doi.org/10.1007/s10689-013-9697-9

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