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Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers

  • Epidemiology
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Abstract

Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in BRCA1 or BRCA2 (BRCA1/2) mutation carriers. Occult ovarian/fallopian tube cancers (OOC) detected at the time of RRSO have been reported in several studies with wide variability in reported prevalence. We estimated the prevalence of OOC in a prospective cohort of 647 BRCA1/2 mutation carriers from 18 centers (PROSE consortium) who underwent RRSO between 2001 and 2008. OOC was detected in 16 of 647 women (2.5%). The mean age at RRSO was 51.7 in those with OOC versus 46.6 in those without OOC (P = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with BRCA1 mutations. Thirty-eight percent of women with OOC had stage 1 cancer versus none of the women in the PROSE database diagnosed with ovarian cancer outside of screening. Among 385 women (60%) in whom pathology reports were available for central review, 246 (64%) RRSOs were performed at participating PROSE centers while 139 (36%) were performed at local sites. Ovarian and fallopian tube tissues removed at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at non-referral centers (75% vs. 30%, P < 0.001). Our results confirm that OOC may be found at the time of RRSO in BRCA1/2 mutation carriers and suggest that OOC are of a more favorable stage than cancers found outside RRSO. An unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO.

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Acknowledgments

All participants provided written informed consent for participation in this study using protocols approved by the Institutional Review Boards of each contributing institution. In addition, the University of Pennsylvania Institutional Review Board approved the overall data collection and analysis protocol for the collaborative data. This study was supported by grants from the Public Health Service (R01-CA83855 and R01-CA102776 to TRR; CA74415 to SLN), the University of Pennsylvania Cancer Center (to TRR), the Cancer Genetics Network (to SMD and CI) the Dana-Farber Women’s Cancers Program (to JEG), the Department of Defense (DAMD-17-96-I-6088 to AKG; DAMD-17-94-J-4340 and DAMD-17-97-I-7112 to HTL; DAMD-17-03-1-0619 to SMD), The Utah Cancer registry (funded by Public Health Service Grant NO1-CN-6700), the Utah State Department of Health,), the National Cancer Institute (2 P30 CA51008-15 to CI) and the Nebraska State Cancer and Smoking-Related Diseases Research Program (LB595 to HTL). DGE is supported by the NIHR Biomedical Research centre at Central Manchester Foundation Trust. OIO is Doris Duke Distinguished Clinical Scientist. None of these funding agencies had involvement in the study design; collection, analysis, or interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication.

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Authors and Affiliations

  1. Abramson Cancer Center, The University of Pennsylvania School of Medicine, 3W Perelman Center, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA

    Susan M. Domchek, Stephen Rubin & Timothy R. Rebbeck

  2. Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Tara M. Friebel & Timothy R. Rebbeck

  3. Dana Farber Cancer Institute, Boston, MA, USA

    Judy E. Garber

  4. Lombardi Cancer Center, Georgetown University, Washington, DC, USA

    Claudine Isaacs

  5. Yale University, New Haven, CT, USA

    Ellen Matloff

  6. The Institute of Cancer Research and the Royal Marsden NHS Trust Foundation, Sutton, Surrey, UK

    Rosalind Eeles

  7. St. Mary’s Hospital, Manchester, UK

    D. Gareth Evans

  8. Northshore University Health System, Evanston, IL, USA

    Wendy Rubinstein

  9. University of Vienna, Vienna, Austria

    Christian F. Singer

  10. Creighton University, Omaha, NE, USA

    Henry T. Lynch

  11. Fox Chase Cancer Center, Philadelphia, PA, USA

    Mary B. Daly

  12. City of Hope National Medical Center, Duarte, CA, USA

    Jeffrey Weitzel

  13. Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA

    Patricia A. Ganz

  14. Guy’s Hospital, London, UK

    Gabriella Pichert

  15. University of Chicago, Chicago, IL, USA

    Olufunmilayo I. Olopade

  16. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Gail Tomlinson

  17. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Nadine Tung

  18. Baylor-Charles A. Sammons Cancer Center, Dallas, TX, USA

    Joanne L. Blum

  19. Mayo Clinic College of Medicine, Rochester, MN, USA

    Fergus Couch

Authors
  1. Susan M. Domchek
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  2. Tara M. Friebel
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  3. Judy E. Garber
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  4. Claudine Isaacs
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  5. Ellen Matloff
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  6. Rosalind Eeles
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  7. D. Gareth Evans
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  8. Wendy Rubinstein
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  9. Christian F. Singer
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  10. Stephen Rubin
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  11. Henry T. Lynch
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  12. Mary B. Daly
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  14. Patricia A. Ganz
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  15. Gabriella Pichert
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  16. Olufunmilayo I. Olopade
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  17. Gail Tomlinson
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  18. Nadine Tung
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  19. Joanne L. Blum
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  20. Fergus Couch
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  21. Timothy R. Rebbeck
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Corresponding author

Correspondence to Susan M. Domchek.

Additional information

This study is conducted for the PROSE Consortium. The details of the PROSE Consortium are listed in Appendix.

Appendix

Appendix

The PROSE Consortium includes the following centers and individuals: Baylor-Charles A. Sammons Cancer Center (Joanne L. Blum, M.D. Ph.D., Becky Althaus, R.N., C.G.C., Gaby Ethington), Baylor College of Medicine (Sharon Plon, M.D., Ph.D., Claire Noll), Beth Israel Deaconess Medical Center (Nadine Tung, M.D.), City of Hope National Medical Center (Jeffery Weitzel, M.D., Veronica Lagos), Creighton University (Henry T. Lynch, M.D., Patrice Watson, Ph.D., Carrie Snyder, B.A.,), Dana Farber Cancer Institute (Judy E. Garber, M.D., M.P.H., Katherine Corso, Kathryn Stoeckert), Duke University (Joellen Schildkraut, Ph.D.), Northshore University Health System (Wendy Rubinstein, M.D., Tina Selkirk), Fox Chase Cancer Center (Mary B. Daly, M.D., Ph.D., Irene Angel), Georgetown University (Claudine Isaacs, M.D., Grace Zawistowski,), Guys and St. Thomas Foundation Trust (Gabriella Pichert, M.D., Caroline Langman, Leena Gohil) Jonsson Comprehensive Cancer Center at the University of California, Los Angeles (Patricia A. Ganz, M.D., Joyce Seldon), Mayo Clinic College of Medicine (Fergus Couch, Ph.D.), Netherlands Cancer Institute (Marc van Beurden M.D., Ph.D., Laura van ‘t Veer, Ph.D.), Royal Marsden Hospital (Rosalind Eeles, M.D., Elizabeth Bancroft), St. Mary’s Hospital (Gareth Evans, M.D., Andrew Shenton), University of Chicago (Shelly Cummings, Olufunmilayo Olopade, M.D.), University of California, Irvine (Susan L. Neuhausen, Ph.D., Linda Steele), University of Pennsylvania (Susan Domchek, M.D., Tara Friebel, M.P.H., Timothy Rebbeck, Ph.D.), University of Texas, Southwestern (Gail Tomlinson, M.D.), University of Vienna (Christian F. Singer, Georg Pfeiler), Women’s College Hospital (Steven A. Narod, M.D.), Yale University (Ellen Matloff, M.S., Karina Brierly).

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Domchek, S.M., Friebel, T.M., Garber, J.E. et al. Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers. Breast Cancer Res Treat 124, 195–203 (2010). https://doi.org/10.1007/s10549-010-0799-x

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