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Breast cancer risk after age 60 among BRCA1 and BRCA2 mutation carriers

  • Epidemiology
  • Published:
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Abstract

Purpose

It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80.

Methods

Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk.

Results

Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk.

Conclusions

Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Code availability

Available from the corresponding author upon reasonable request.

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Acknowledgements

Steven A. Narod is the recipient of a Canada Research Chair (Tier I). Joanne Kotsopoulos is the recipient of a Canada Research Chair (Tier II).

Other members of the Hereditary Breast Cancer Clinical Study Group: Leigha Senter, Charis Eng Fergus Couch, Robert Fruscio, Jeffrey N. Weitzel Olufunmilayo Olopade, Christian F. Singer, Tuya Pal, Tomasz Huzarski, Cezary Cybulski, Kevin Sweet, Dana Zakalik, Marie Wood, Wendy McKinnon, Christine Elser, Georgia Wiesner, Eitan Friedman, Wendy Meschino, Carrie Snyder, Kelly Metcalfe, Aletta Poll, Ellen Warner, Raymond Kim, Rochelle Demsky, Peter Ainsworth, Linda Steele, Howard Saal, Kim Serfas, Seema Panchal, Carey A. Cullinane, Robert E. Reilly, Joanne L. Blum, Ava Kwong, Daniel Rayson, Teresa Ramón y Cajal, Jeffrey Dungan, Rinat Yerushalmi, Ophira Ginsburg, Intan Schraeder, Stephanie Cohen, Edmond Lemire, Stefania Zovato, Antonella Rastelli, Jacek Gronwald, Jeanna McCuaig, Beth Karlan, Louise Bordeleau.

Funding

This work was supported by the Canadian Institutes of Health Research (FDN 154275), Canadian Cancer Society Research Institute Grant (703058) and the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital, in partnership with the Canadian Cancer Society.

Author information

Authors and Affiliations

  1. Toronto-Sunnybrook Regional Cancer Center, Toronto, ON, Canada

    Neda Stjepanovic & Andrea Eisen

  2. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

    Jan Lubinski

  3. Department of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Pal Moller

  4. University Health Network, Toronto, ON, Canada

    Susan Randall Armel

  5. Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, QC, Canada

    William D. Foulkes

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

    Nadine Tung

  7. Division of Biomarkers of Early Detection and Prevention, Department of Population Sciences, City of Hope, Duarte, CA, USA

    Susan L. Neuhausen

  8. Women’s College Research Institute, Women’s College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada

    Joanne Kotsopoulos, Ping Sun & Steven A. Narod

  9. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Joanne Kotsopoulos & Steven A. Narod

  10. BC Cancer Agency, Vancouver, BC, Canada

    Sophie Sun

Authors
  1. Neda Stjepanovic
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  2. Jan Lubinski
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  3. Pal Moller
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  4. Susan Randall Armel
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  5. William D. Foulkes
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  6. Nadine Tung
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  7. Susan L. Neuhausen
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  8. Joanne Kotsopoulos
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  9. Ping Sun
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  10. Sophie Sun
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  11. Andrea Eisen
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  12. Steven A. Narod
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Consortia

the Hereditary Breast Cancer Clinical Study Group

  • Leigha Senter
  • , Charis Eng Fergus Couch
  • , Robert Fruscio
  • , Jeffrey N. Weitzel
  • , Olufunmilayo Olopade
  • , Christian F. Singer
  • , Tuya Pal
  • , Tomasz Huzarski
  • , Cezary Cybulski
  • , Kevin Sweet
  • , Dana Zakalik
  • , Marie Wood
  • , Wendy McKinnon
  • , Christine Elser
  • , Georgia Wiesner
  • , Eitan Friedman
  • , Wendy Meschino
  • , Carrie Snyder
  • , Kelly Metcalfe
  • , Aletta Poll
  • , Ellen Warner
  • , Raymond Kim
  • , Rochelle Demsky
  • , Peter Ainsworth
  • , Linda Steele
  • , Howard Saal
  • , Kim Serfas
  • , Seema Panchal
  • , Carey A. Cullinane
  • , Robert E. Reilly
  • , Joanne L. Blum
  • , Ava Kwong
  • , Daniel Rayson
  • , Teresa Ramón y Cajal
  • , Jeffrey Dungan
  • , Rinat Yerushalmi
  • , Ophira Ginsburg
  • , Intan Schraeder
  • , Stephanie Cohen
  • , Edmond LemireLemire
  • , Stefania Zovato
  • , Antonella Rastelli
  • , Jacek Gronwald
  • , Jeanna McCuaig
  • , Beth Karlan
  •  & Louise Bordeleau

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by NS, AE, SN and PS. The first draft of the manuscript was written by NS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Steven A. Narod.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Women’s College Hospital Ethics Board. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.

Consent to participate

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

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The members of the Hereditary Breast Cancer Clinical Study Group have been listed in acknowledgements.

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Stjepanovic, N., Lubinski, J., Moller, P. et al. Breast cancer risk after age 60 among BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 187, 515–523 (2021). https://doi.org/10.1007/s10549-020-06072-9

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  • DOI: https://doi.org/10.1007/s10549-020-06072-9

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