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Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The impact of ATM, CHEK2, and PALB2, the three most prevalent moderate-risk breast cancer genes, on surgical decision making is not well known.

Methods

Our retrospective study included patients with resectable non-metastatic breast cancer who underwent multigene panel testing between July 2014 and January 2020 with at least one genetic alteration (pathogenic or variant of uncertain significance [VUS] in ATM [n = 49], CHEK [n = 57], or PALB2 [n = 27]). Our objectives were to determine the rate of contralateral prophylactic mastectomy (CPM) and the rate of bilateral breast cancer. Univariable analyses (UVA) and multivariable analyses (MVA) were performed to identify factors associated with CPM and bilateral breast cancer.

Results

The rate of CPM was 39% (n = 49/127), with 54% (n = 25/46) of patients with a pathogenic mutation and 30% (n = 24/81) of patients with a VUS choosing CPM. On MVA, premenopausal status (odds ratio [OR] 3.46) and a pathogenic alteration (OR 3.01) were associated with increased use of CPM. Bilateral disease was noted in 16% (n = 22/138). Patients with pathogenic mutations had a 22% (n = 11/51) incidence of bilateral breast cancer, while patients with VUS had a 13% (n = 11/87) incidence, although this was not statistically significant on UVA or MVA. On MVA, premenopausal status was associated with a decreased risk of bilateral disease (OR 0.33, p = 0.022). During follow-up, a breast cancer event occurred in 16% (n = 22/138).

Conclusions

Our study identified a high rate of CPM among those with ATM, CHEK2, and PALB2 alterations, including VUS. Further studies are needed to clarify reasons for CPM among patients with moderate-risk alterations.

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Acknowledgments

The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center, and this study was presented in poster format at the Society of Surgical Oncology 2022 International Conference on Surgical Cancer Care, March 9–12, 2022, Dallas, TX.

Author information

Author notes

  1. Jennifer Q. Zhang, Carlos Henrique Dos Anjos, Mary L. Gemignani, and Mark E. Robson have contributed equally to this work.

Authors and Affiliations

  1. Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jennifer Q. Zhang MD, Angelena Crown MD, Melissa L. Pilewskie MD & Mary L. Gemignani MD, MPH

  2. Department of Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia, PA, USA

    Jennifer Q. Zhang MD

  3. Oncology Service, Hospital Sirio-Libanes, São Paulo, Brazil

    Carlos Henrique Dos Anjos MD

  4. Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Varadan Sevilimedu MBBS, DrPH

  5. Breast Surgery, True Family Women’s Cancer Center, Swedish Cancer Institute, Seattle, WA, USA

    Angelena Crown MD

  6. Clinical Genetics Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kimberly A. Amoroso MS, CGC

  7. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Melissa L. Pilewskie MD

  8. Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mark E. Robson MD

Authors
  1. Jennifer Q. Zhang MD
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  2. Carlos Henrique Dos Anjos MD
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  3. Varadan Sevilimedu MBBS, DrPH
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  4. Angelena Crown MD
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  6. Melissa L. Pilewskie MD
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  7. Mark E. Robson MD
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  8. Mary L. Gemignani MD, MPH
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Corresponding author

Correspondence to Jennifer Q. Zhang MD.

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Disclosures

Dr. Mark E. Robson reports uncompensated provision of services to Artios Pharma Limited, AstraZeneca, Tempus Labs, Inc., Pfizer, Inc., and Zenith Pharma, Inc., and honoraria from Clinical Education Alliance, LLC, Genome Quebec, MJH Associates, Physicians’ Education Resources, and Change Healthcare Inc. Dr. Carlos Henrique Dos Anjos reports the following speaking engagements: AstraZeneca, Daiichi-Sankyo, Pfizer, MDHealth, Springer Healthcare, MSD, Roche, Lilly, Gilead, and Fleury. All other authors have no conflicts of interest to disclose.

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Zhang, J.Q., Dos Anjos, C.H., Sevilimedu, V. et al. Association of Moderate-Risk Breast Cancer Genes with Contralateral Prophylactic Mastectomy and Bilateral Disease. Ann Surg Oncol 30, 6990–6999 (2023). https://doi.org/10.1245/s10434-023-14141-8

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  • DOI: https://doi.org/10.1245/s10434-023-14141-8

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