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Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers

Abstract

Purpose

Identification of inherited breast cancer may guide cancer risk management. We sought to compare risk management practices across women with inherited breast cancer genes.

Methods

Females with a pathogenic/likely pathogenic (P/LP) variant in BRCA1/2, PALB2, CHEK2, and/or ATM were surveyed about cancer risk management. Comparisons were made across genes.

Results

The 235 participants with P/LP variants (186 BRCA1/2, 28 PALB2, 15 CHEK2, and 6 ATM) had a median age of 54 and 61% had a prior breast cancer diagnosis. For women with P/LP variants in BRCA1/2, PALB2, and ATM/CHEK2, bilateral mastectomy (BM) rates were 79%, 61%, and 52%, and bilateral oophorectomy (BO) rates were 89%, 30%, and 37%, respectively. Among women with P/LP variants in PALB2 and ATM/CHEK2, 27% of those who had a BO had a family history of ovarian cancer. Contralateral mastectomy rates for women with P/LP variants in PALB2 and ATM/CHEK2 with unilateral breast cancer were 60% and 58%, and BM rates for those without breast cancer were 57% and 29%, respectively.

Conclusion

These findings suggest high rates of both contralateral mastectomies among those with unilateral breast cancer and BM among those without a breast cancer diagnosis across women with P/LP variants in high and moderate penetrance breast cancer genes. BO was also often utilized for risk reduction across these women. These findings suggest potential overtreatment through risk-reducing surgery, and highlight the importance of promoting guideline-adherent, risk-appropriate care.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Acknowledgements

Funding for this study was supported in part by the National Cancer Institute (NCI) VICC Specialized Program of Research Excellence (SPORE) in Breast Cancer (P50CA098131), the Ingram Professorship, the Kleberg Foundation, Vanderbilt Genetic Institute departmental funds, and a 2018 USF COPH Faculty Research Award.

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Authors and Affiliations

Authors

Contributions

DC: Conceptualization, funding acquisition, formal analysis, writing – original draft, and writing—review and editing. AW: Data curation, formal analysis, project administration, and writing—review and editing. AT: Data curation, project administration, and writing—review and editing. KC: Writing—review and editing. TP: Conceptualization, funding acquisition, writing—original draft, and writing—review and editing.

Corresponding author

Correspondence to Tuya Pal.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The methodology for this study was approved by the Institutional Review Boards at Vanderbilt University (IRB # 180420) and the University of South Florida (IRB # Pro00037381). 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.

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

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Cragun, D., Weidner, A., Tezak, A. et al. Cancer risk management among female BRCA1/2, PALB2, CHEK2, and ATM carriers. Breast Cancer Res Treat 182, 421–428 (2020). https://doi.org/10.1007/s10549-020-05699-y

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  • DOI: https://doi.org/10.1007/s10549-020-05699-y

Keywords

  • Genetic testing
  • Germline mutation
  • Breast cancer
  • Disease management
  • Public health