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Contralateral Risk-Reducing Mastectomy in Breast Cancer Patients Who Undergo Multigene Panel Testing

Abstract

Background

An increasing number of breast cancer patients are undergoing expanded genetic testing and are being identified as germline mutation carriers. We sought to determine rates of contralateral risk-reducing mastectomy (CRRM) in patients with various germline mutations.

Patients and Methods

All women ≥ 18 years of age with unilateral breast cancer who underwent multigene panel testing between January 1, 2014 and August 1, 2019 at our academic institution were identified. Demographic, tumor, and treatment variables were identified from the medical record. Multivariable analyses were performed to compare factors associated with performance of CRRM.

Results

We identified 1613 patients, of whom 28.1% had a pathogenic variant and 40.1% had variants of uncertain significance (VUS). Overall, 420 patients (26.0%) underwent a CRRM. On multivariable analysis, factors associated with CRRM included age < 50 years (OR 3.8, 95% CI 3.0, 5.0), race (OR 0.5, 95% CI 0.3, 0.7 and OR 0.4, 95% CI 0.2, 0.7 for Black and Asian women, respectively, versus White women), and the presence of any germline mutation or VUS (OR 13.2, 95% CI 8.7, 20.2 for BRCA1/2; OR 3.9, 95% CI 2.7, 5.8 for non-BRCA germline mutation; and OR 1.8, 95% CI 1.3, 2.6 for VUS).

Conclusions

In breast cancer patients who undergo multigene panel testing, a sizeable number of women with pathogenic non-BRCA germline findings are opting for CRRM. Given that the risk of contralateral breast cancer in women with most pathogenic mutations other than BRCA1/2 remains poorly characterized, these data have implications for risk counseling and for ascertaining the true risks of contralateral breast cancer in this population.

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References

  1. 1.

    National Cancer Institute, Cancer Stat Facts: Female Breast Cancer. 2020. https://seer.cancer.gov/statfacts/html/breast.html.

  2. 2.

    Alaofi RK, Nassif MO, Al-Hajeili MR. Prophylactic mastectomy for the prevention of breast cancer: Review of the literature. Avicenna J Med. 2018;8(3):67–77.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    AlHilli MM, Al-Hilli Z. Perioperative management of women undergoing risk-reducing surgery for hereditary breast and ovarian cancer. J Minim Invasive Gynecol. 2019;26(2):253–65.

    PubMed  Article  Google Scholar 

  4. 4.

    National Comprehensive Cancer Network, Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. 2019; Vol. 1.2020. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf.

  5. 5.

    Manahan ER, Kuerer HM, Sebastian M, et al. Consensus guidelines on genetic testing for hereditary breast cancer from the American Society of Breast Surgeons. Ann Surg Oncol. 2019;26(10):3025–31.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Young C, Argaez C. CADTH Rapid Response Reports. In Rapid genome-wide testing: A review of clinical utility, cost-effectiveness, and guidelines. Canadian Agency for Drugs and Technologies in Health Copyright© 2019 Canadian Agency for Drugs and Technologies in Health: Ottawa (ON), 2019.

  7. 7.

    Kurian AW, Li Y, Hamilton AS, et al. Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol. 2017;35(20):2232–9.

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Chang J, Seng S, Yoo J, et al. Clinical management of patients at risk for hereditary breast cancer with variants of uncertain significance in the era of multigene panel testing. Ann Surg Oncol. 2019;26(10):3389–96.

    PubMed  Article  Google Scholar 

  9. 9.

    Theobald KA, Susswein LR, Marshall ML, et al. Utility of expedited hereditary cancer testing in the surgical management of patients with a new breast cancer diagnosis. Ann Surg Oncol. 2018;25(12):3556–62.

    PubMed  Article  Google Scholar 

  10. 10.

    Elsayegh N, Webster RD, Gutierrez Barrera AM, et al. Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer. Cancer Med. 2018;7(6):2718–26.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Akaike H. A new look at the statistical model identification. IEEE Trans Automat Contr. 1974;19:716–723.

    Article  Google Scholar 

  12. 12.

    Chen H, Zhang P, Zhang M, et al. Growing trends of contralateral prophylactic mastectomy and reconstruction in young breast cancer. J Surg Res. 2019;239:224–232.

    PubMed  Article  Google Scholar 

  13. 13.

    Zhang B, Coopey SB, Gadd MA, et al. Trends in unilateral and contralateral prophylactic mastectomy use in ductal carcinoma in situ of the breast: patterns and predictors. Ann Surg Oncol. 2019;26(12):3863–73.

    PubMed  Article  Google Scholar 

  14. 14.

    Beitsch PD, Whitworth PW, Hughes K, et al. Underdiagnosis of hereditary breast cancer: Are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 2019;37(6):453–60.

    PubMed  Article  Google Scholar 

  15. 15.

    Buys SS, Sandbach JF, Gammon A, et al. A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer. 2017;123(10):1721–30.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Green L, Meric-Bernstam F. Risk of ipsilateral and contralateral cancer in BRCA mutation carriers with breast cancer. Curr Breast Cancer Rep. 2011;3(3):151–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA. 2017;317(23):2402–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    National Comprehensive Cancer Network, Breast Cancer Risk Reduction. 2020. https://www.nccn.org/professionals/physician_gls/pdf/breast_risk_blocks.pdf.

  19. 19.

    Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27(35):5887–92.

    PubMed  Article  Google Scholar 

  20. 20.

    Metcalfe K, Gershman S, Lynch HT, et al. Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2011;104(9);1384–92.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Song CV, Teo SH, Taib NA, et al. Surgery for BRCA, TP53 and PALB2: a literature review. Ecancermedicalscience. 2018;12:863.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Teoh V, Tasoulis MK, Gui G. Contralateral prophylactic mastectomy in women with unilateral breast cancer who are genetic carriers, have a strong family history or are just young at presentation. Cancers. 2020;12(1).

  23. 23.

    Evans DG, Ingham SL, Baildam A, et al. Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer. Breast Cancer Res Treat. 2013;140(1):135–42.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Heemskerk-Gerritsen BA, Rookus MA, Aalfs CM, et al. Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis. Int J Cancer. 2015;136(3):668–77.

    CAS  PubMed  Google Scholar 

  25. 25.

    Metcalfe K, Gershman S, Ghadirian P, et al. Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ (Clin Res Ed). 2014;348:g226.

    Google Scholar 

  26. 26.

    Passaperuma K, Warner E, Causer PA, et al. Long-term results of screening with magnetic resonance imaging in women with BRCA mutations. Br J Cancer 2012;107(1):24–30.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Warner E. Impact of MRI surveillance and breast cancer detection in young women with BRCA mutations. Ann Oncol 2011;22(Suppl 1):i44–9.

    PubMed  Article  Google Scholar 

  28. 28.

    Bernstein JL, Concannon P. ATM, radiation, and the risk of second primary breast cancer. Int J Rad Biol. 2017;93(10):1121–1127.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Broeks A, de Witte L, Nooijen A, et al. Excess risk for contralateral breast cancer in CHEK2*1100delC germline mutation carriers. Breast Cancer Res Treat. 2004;83(1):91–3.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Kriege M, Hollestelle A, Jager A, et al. Survival and contralateral breast cancer in CHEK2 1100delC breast cancer patients: impact of adjuvant chemotherapy. Br J Cancer. 2014;111(5):1004–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Weischer M, Nordestgaard BG, Pharoah P, et al. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol. 2012;30(35):4308–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Couch FJ, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 2017;3(9):1190–6.

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Yadav S, Couch FJ. Germline genetic testing for breast cancer risk: the past, present, and future. Am Soc Clin Oncol. 2019;39:61–74.

    Article  Google Scholar 

  34. 34.

    Parker PA, Peterson SK, Bedrosian I, et al. Prospective study of surgical decision-making processes for contralateral prophylactic mastectomy in women with breast cancer. Ann Surg. 2016;263(1):178–83.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Pederson HJ, Gopalakrishnan D, Noss R, et al. Impact of multigene panel testing on surgical decision making in breast cancer patients. J Am Coll Surg. 2018;226(4):560–5.

    PubMed  Article  Google Scholar 

  36. 36.

    Welsh JL, Hoskin TL, Day CN, et al. Clinical decision-making in patients with variant of uncertain significance in BRCA1 or BRCA2 genes. Ann Surg Oncol. 2017;24(10):3067–72.

    PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24.

    PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgment

The authors thank Rachel Hicklen with the MD Anderson Cancer Center Research Medical Library Literature Search Services for her assistance in the literature search for this manuscript.

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Correspondence to Isabelle Bedrosian MD.

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Murphy, B.L., Yi, M., Arun, B.K. et al. Contralateral Risk-Reducing Mastectomy in Breast Cancer Patients Who Undergo Multigene Panel Testing. Ann Surg Oncol 27, 4613–4621 (2020). https://doi.org/10.1245/s10434-020-08889-6

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