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Oophorectomy and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers

  • Joanne Kotsopoulos
  • Jan Lubinski
  • Henry T. Lynch
  • Nadine Tung
  • Susan Armel
  • Leigha Senter
  • Christian F. Singer
  • Robert Fruscio
  • Fergus Couch
  • Jeffrey N. Weitzel
  • Beth Karlan
  • William D. Foulkes
  • Pal Moller
  • Andrea Eisen
  • Peter Ainsworth
  • Susan L. Neuhausen
  • Olufunmilayo Olopade
  • Ping Sun
  • Jacek Gronwald
  • Steven A. NarodEmail author
  • the Hereditary Breast Cancer Clinical Study Group
Epidemiology

Abstract

Purpose

Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer.

Methods

Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire).

Results

After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68–1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240).

Conclusion

Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer.

Keywords

BRCA1/2 Oophorectomy Contralateral breast cancer 

Notes

Acknowledgements

We would like to acknowledge the study staff, students, and volunteers including Shana Kim, Farah Shoukat, Ellen MacDougall, Zoella Pasta, Nida Mian, Jennifer Ng, Sarah Chin, Hamida Begum, Harmeet Chaudhary, Asrafi Azmi, Shahana Nargis, Clotilde Ngwa, Mai Abdelhadi, Saiveena Penikalapati, Laavanya Somasundaram, and Hannah Horvath who helped with the data collection and data entry.

Other members of the Hereditary Breast Cancer Clinical Study Group: Tuya Pal, Georgia Wiesner, Charis Eng, Louise Bordeleau, Eitan Friedman, Wendy Meschino, Carrie Snyder, Kelly Metcalfe, Aletta Poll, Nicole Gojska, Ellen Warner, Barry Rosen, Jeanna McCuaig, Susan Armel, Rochelle Demsky, Karen Panabaker, Linda Steele, Howard Saal, Marie Wood, Wendy McKinnon, Edmond Lemire, Kim Serfas, Kevin Sweet, Seema Panchal, Christine Elser, Carey A. Cullinane, Robert E. Reilly, Joanne L. Blum, Ava Kwong, Cezary Cybulski, Tomasz Huzarski, Daniel Rayson, Claudine Isaacs, Teresa Ramón y Cajal, Jeffrey Dungan, Dana Zakalik, and Stephanie Cohen.

Funding

Joanne Kotsopoulos is a recipient of a Tier II Canada Research Chair. Steven A. Narod is the recipient of a Tier I Canada Research Chair. This study was supported by a Canadian Cancer Society Research Institute Grant (703058), the Peter Gilgan Foundation, and by a “Pink ribbon” grant (194751) from Den Norske Kreftforening to E.H.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Joanne Kotsopoulos
    • 1
    • 2
  • Jan Lubinski
    • 3
  • Henry T. Lynch
    • 4
  • Nadine Tung
    • 5
  • Susan Armel
    • 6
  • Leigha Senter
    • 7
  • Christian F. Singer
    • 8
  • Robert Fruscio
    • 9
  • Fergus Couch
    • 10
  • Jeffrey N. Weitzel
    • 11
  • Beth Karlan
    • 12
  • William D. Foulkes
    • 13
  • Pal Moller
    • 14
  • Andrea Eisen
    • 15
  • Peter Ainsworth
    • 16
  • Susan L. Neuhausen
    • 17
  • Olufunmilayo Olopade
    • 18
  • Ping Sun
    • 1
  • Jacek Gronwald
    • 3
  • Steven A. Narod
    • 1
    • 2
    Email author
  • the Hereditary Breast Cancer Clinical Study Group
  1. 1.Women’s College Research InstituteWomen’s College HospitalTorontoCanada
  2. 2.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada
  3. 3.International Hereditary Cancer Center, Department of Genetics and PathologyPomeranian Medical UniversitySzczecinPoland
  4. 4.Department of Preventive Medicine and Public HealthCreighton University School of MedicineOmahaUSA
  5. 5.Beth Israel Deaconess Medical CenterBostonUSA
  6. 6.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyUniversity of TorontoTorontoCanada
  7. 7.Division of Human Genetics, Comprehensive Cancer CenterThe Ohio State University Medical CenterColumbusUSA
  8. 8.Department of Obstetrics and Gynecology and Comprehensive Cancer CenterMedical University of ViennaViennaAustria
  9. 9.Department of Medicine and SurgeryUniversity of Milan BicoccaMilanItaly
  10. 10.Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  11. 11.Division of Clinical Cancer Genomics, Department of Population SciencesCity of HopeDuarteUSA
  12. 12.Gynecology OncologyCedars Sinai Medical CenterLos AngelesUSA
  13. 13.Program in Cancer Genetics, Department of Oncology and Human GeneticsMcGill UniversityMontrealCanada
  14. 14.Inherited Cancer Research Group, Department for Medical Genetics, Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, The Norwegian Radium HospitalOslo University HospitalOsloNorway
  15. 15.Toronto-Sunnybrook Regional Cancer CenterTorontoCanada
  16. 16.Department of Pathology and Laboratory MedicineWestern UniversityLondonCanada
  17. 17.Division of Biomarkers of Early Detection and Prevention, Department of Population ScienceCity of HopeDuarteUSA
  18. 18.Department of Medicine and Human GeneticsUniversity of ChicagoChicagoUSA

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