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



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


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.


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.


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.


  1. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71

    CAS  Article  PubMed  Google Scholar 

  2. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792.

    CAS  Article  PubMed  Google Scholar 

  3. Kurian AW, Ward KC, Howlader N, Deapen D, Hamilton AS, Mariotto A, Miller D, Penberthy LS, Katz SJ (2019) Genetic testing and results in a population-based cohort of breast cancer patients and ovarian cancer patients. J Clin Oncol 37(15):1305–1315.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Robson ME, Bradbury AR, Arun B, Domchek SM, Ford JM, Hampel HL, Lipkin SM, Syngal S, Wollins DS, Lindor NM (2015) American society of clinical oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 33(31):3660–3667.

    CAS  Article  PubMed  Google Scholar 

  5. Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533.

    CAS  Article  PubMed  Google Scholar 

  6. Kurian AW, Ward KC, Hamilton AS, Deapen DM, Abrahamse P, Bondarenko I, Li Y, Hawley ST, Morrow M, Jagsi R, Katz SJ (2018) Uptake, results, and outcomes of germline multiple-gene sequencing after diagnosis of breast cancer. JAMA Oncol 4(8):1066–1072.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Couch FJ, Shimelis H, Hu C, Hart SN, Polley EC, Na J, Hallberg E, Moore R, Thomas A, Lilyquist J, Feng B, McFarland R, Pesaran T, Huether R, LaDuca H, Chao EC, Goldgar DE, Dolinsky JS (2017) Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 3(9):1190–1196.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25(11):1329–1333.

    Article  PubMed  Google Scholar 

  9. King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646.

    CAS  Article  PubMed  Google Scholar 

  10. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, Jervis S, van Leeuwen FE, Milne RL, Andrieu N, Goldgar DE, Terry MB, Rookus MA, Easton DF, Antoniou AC, McGuffog L, Evans DG, Barrowdale D, Frost D, Adlard J, Ong KR, Izatt L, Tischkowitz M, Eeles R, Davidson R, Hodgson S, Ellis S, Nogues C, Lasset C, Stoppa-Lyonnet D, Fricker JP, Faivre L, Berthet P, Hooning MJ, van der Kolk LE, Kets CM, Adank MA, John EM, Chung WK, Andrulis IL, Southey M, Daly MB, Buys SS, Osorio A, Engel C, Kast K, Schmutzler RK, Caldes T, Jakubowska A, Simard J, Friedlander ML, McLachlan SA, Machackova E, Foretova L, Tan YY, Singer CF, Olah E, Gerdes AM, Arver B, Olsson H (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416.

    CAS  Article  PubMed  Google Scholar 

  11. Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, Dunning AM, Redman J, Scarth J, Plaskocinska I, Luccarini C, Shah M, Pooley K, Dorling L, Lee A, Adank MA, Adlard J, Aittomäki K, Andrulis IL, Ang P, Barwell J, Bernstein JL, Bobolis K, Borg Å, Blomqvist C, Claes KBM, Concannon P, Cuggia A, Culver JO, Damiola F, Pauw Ad, Diez O, Dolinsky JS, Domchek SM, Engel C, Evans DG, Fostira F, Garber J, Golmard L, Goode EL, Gruber SB, Hahnen E, Hake C, Heikkinen T, Hurley JE, Janavicius R, Kleibl Z, Kleiblova P, Konstantopoulou I, Kvist A, Laduca H, Lee ASG, Lesueur F, Maher ER, Mannermaa A, Manoukian S, McFarland R, McKinnon W, Meindl A, Metcalfe K, Taib NAM, Moilanen J, Nathanson KL, Neuhausen S, Ng PS, Nguyen-Dumont T, Nielsen SM, Obermair F, Offit K, Olopade OI, Ottini L, Penkert J, Pylkäs K, Radice P, Ramus SJ, Rudaitis V, Side L, Silva-Smith R, Silvestri V, Skytte A-B, Slavin T, Soukupova J, Tondini C, Trainer AH, Unzeitig G, Usha L, TvO H, Whitworth J, Wood M, Yip CH, Yoon S-Y, Yussuf A, Zogopoulos G, Goldgar D, Hopper JL, Chenevix-Trench G, Pharoah P, George SHL, Balmaña J, Houdayer C, James P, El-Haffaf Z, Ehrencrona H, Janatova M, Peterlongo P, Nevanlinna H, Schmutzler R, Teo S-H, Robson M, Pal T, Couch F, Weitzel JN, Elliott A, Southey M, Winqvist R, Easton DF, Foulkes WD, Antoniou AC, Tischkowitz M (2020) Cancer risks associated with germline PALB2 pathogenic variants: an international study of 524 families. J Clin Oncol 38(7):674–685.

    Article  PubMed  Google Scholar 

  12. Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, Devilee P, Meindl A, Couch FJ, Southey M, Goldgar DE, Evans DG, Chenevix-Trench G, Rahman N, Robson M, Domchek SM, Foulkes WD (2015) Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med 372(23):2243–2257.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Lu HM, Li S, Black MH, Lee S, Hoiness R, Wu S, Mu W, Huether R, Chen J, Sridhar S, Tian Y, McFarland R, Dolinsky J, Tippin Davis B, Mexal S, Dunlop C, Elliott A (2019) Association of breast and ovarian cancers with predisposition genes identified by large-scale sequencing. JAMA Oncol 5(1):51–57.

    Article  PubMed  Google Scholar 

  14. National Comprehensive Cancer Network (NCCN) (2020) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic V.1.2020. NCCN practice guidelines website. Accessed 4 Dec 2019

  15. Schwartz MD, Isaacs C, Graves KD, Poggi E, Peshkin BN, Gell C, Finch C, Kelly S, Taylor KL, Perley L (2012) Long-term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance. Cancer 118(2):510–517.

    Article  PubMed  Google Scholar 

  16. Garcia C, Wendt J, Lyon L, Jones J, Littell RD, Armstrong MA, Raine-Bennett T, Powell CB (2014) Risk management options elected by women after testing positive for a BRCA mutation. Gynecol Oncol 132(2):428–433.

    Article  PubMed  Google Scholar 

  17. Pal T, Radford C, Weidner A, Tezak AL, Cragun D, Wiesner GL (2018) The Inherited cancer registry (ICARE) initiative: an academic-community partnership for patients and providers. Oncol Oncology Issues 33(6):54–63

    Article  Google Scholar 

  18. Cragun D, Weidner A, Lewis C, Bonner D, Kim J, Vadaparampil ST, Pal T (2017) Racial disparities in BRCA testing and cancer risk management across a population-based sample of young breast cancer survivors. Cancer 123(13):2497–2505.

    CAS  Article  PubMed  Google Scholar 

  19. Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski R, Wolitzer AL, Whittemore AS, West D, Seminara D, Olson ER, Spurdle AB, Chenevix-Trench G, Giles GG, Hopper JL, Concannon P (2006) Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T%3eG and c.1066-6T%3eG (IVS10-6T%3eG) from the breast cancer family registry. Hum Mutat 27(11):1122–1128.

    CAS  Article  PubMed  Google Scholar 

  20. Goldgar DE, Healey S, Dowty JG, Da Silva L, Chen X, Spurdle AB, Terry MB, Daly MJ, Buys SM, Southey MC, Andrulis I, John EM, Khanna KK, Hopper JL, Oefner PJ, Lakhani S, Chenevix-Trench G (2011) Rare variants in the ATM gene and risk of breast cancer. Breast Cancer Res 13(4):R73.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Witte K, Cameron KA, McKeon JK, Berkowitz JM (1996) Predicting risk behaviors: development and validation of a diagnostic scale. J Health Commun 1:317–341.

    CAS  Article  PubMed  Google Scholar 

  22. Joshi A, Kale S, Chandel S, Pal DK (2015) Likert Scale: explored and explained. Br J Appl Sci Technol 7:396–403

    Article  Google Scholar 

  23. Buchanan AH, Voils CI, Schildkraut JM, Fine C, Horick NK, Marcom PK, Wiggins K, Skinner CS (2017) Adherence to recommended risk management among unaffected women with a BRCA mutation. J Genet Couns 26(1):79–92.

    Article  PubMed  Google Scholar 

  24. Vysotskaia V, Kaseniit KE, Bucheit L, Ready K, Price K, Johansen Taber K (2019) Clinical utility of hereditary cancer panel testing: Impact of PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D results on patient management and adherence to provider recommendations. Cancer 126(3):549–558.

    CAS  Article  PubMed  Google Scholar 

  25. Kurian AW, Ward KC, Abrahamse P, Hamilton AS, Deapen D, Morrow M, Jagsi R, Katz SJ (2020) Association of germline genetic testing results with locoregional and systemic therapy in patients with breast cancer. JAMA Oncol 6(4):e196400.

    Article  PubMed  PubMed Central  Google Scholar 

  26. MyGeneCounsel (2019) White paper: how often do medical management guidelines change for people with germline genetic findings? A solution for keeping patients and providers updated. Accessed 10 Dec 2019

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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



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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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).

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