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

Breast Cancer Res Treat. 2020 Jul;182(2):421-428. doi: 10.1007/s10549-020-05699-y. Epub 2020 May 22.


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.

Keywords: Breast cancer; Disease management; Genetic testing; Germline mutation; Public health.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / prevention & control*
  • Checkpoint Kinase 2 / genetics
  • Fanconi Anemia Complementation Group N Protein / genetics
  • Female
  • Genetic Carrier Screening / statistics & numerical data
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Guideline Adherence / standards
  • Guideline Adherence / statistics & numerical data
  • Hereditary Breast and Ovarian Cancer Syndrome / diagnosis
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics
  • Hereditary Breast and Ovarian Cancer Syndrome / prevention & control*
  • Heterozygote
  • Humans
  • Medical History Taking
  • Medical Overuse / prevention & control
  • Medical Overuse / statistics & numerical data
  • Ovariectomy / standards
  • Ovariectomy / statistics & numerical data*
  • Practice Guidelines as Topic
  • Practice Patterns, Physicians' / standards
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Prophylactic Mastectomy / standards
  • Prophylactic Mastectomy / statistics & numerical data*
  • Young Adult


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human

Supplementary concepts

  • Breast Cancer, Familial