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Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Comprehensively analyzing the prevalence of BRCA1/2 germline pathogenic variants (PVs) in a large cohort of unselected Chinese patients with breast cancer has great clinical importance.

Methods

Germline pathogenic variants in full-length BRCA1/2 genes were determined through next-generation sequencing and/or Sanger sequencing assays in 8627 unselected Chinese patients with breast cancer who were treated at the Breast Center of Peking University Cancer Hospital. The prevalence of BRCA1/2 PVs was further stratified by age at diagnosis, family history of cancer and molecular subtype.

Results

We found that the overall prevalence of BRCA1/2 PVs was 6.0% in the entire cohort, 2.4% in BRCA1 and 3.7% in BRCA2. The prevalence of BRCA1/2 PVs in patients with early-onset breast cancer (age at diagnosis ≤ 40 years) was significantly higher than that in patients over the age of 40 (9.7% vs. 5.1%). The prevalence rates of BRCA1/2 PVs in patients with a family history of breast, ovarian, pancreatic, and prostate cancer were 19.5%, 39.0%, 11.1%, and 12.8%, respectively. Moreover, the number of relatives affected by breast cancer was associated with a higher prevalence of BRCA1/2 PVs. Molecular subtypes were associated with the prevalence of BRCA1/2 PVs. Patients with the triple-negative phenotype had the highest prevalence of BRCA1/2 PVs (13.3%) among the three molecular groups, followed by the HR + and HER2- group (5.9%), and the lowest was in the HER2 + group (2.5%).

Conclusion

Our study provides the most comprehensive information to date on the prevalence of BRCA1/2 PVs in unselected Chinese patients with breast cancer.

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Data availability

All data and material relevant to the study available from the corresponding authors upon reasonable request.

Abbreviations

EBC:

Early-onset breast cancer

ER:

Estrogen receptor

FBC:

Family history of breast cancer

HER2:

Human epidermal growth factor receptor 2

HR:

Hormone receptor

MLPA:

Multiplex ligation-dependent probe amplification

NGS:

Next-generation sequencing

PARP:

Poly(adenosine diphosphate ribose) polymerase

PR:

Progesterone receptor

PVs:

Pathogenic variants

TNBC:

Triple-negative breast cancer

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Acknowledgements

We thank all individuals who participated in our study.

Funding

This study was supported by Beijing Municipal Administration of Hospitals Incubating Program (No. PX2021042) and National Natural Science Foundation of China (Grant Nos. 81974422, 81772824, 81672625).

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Author notes

  1. Fan Zang and Xinyun Ding have contributed equally to this study. Both Lu Yao and Yuntao Xie are corresponding authors.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China

    Fan Zang, Xinyun Ding, Jiuan Chen, Li Hu, Jie Sun, Juan Zhang, Ye Xu, Lu Yao & Yuntao Xie

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  1. Fan Zang
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Contributions

All authors contributed to the study conception and design. YX: conceptualization, funding acquisition, supervision, writing – review & editing; LY: project administration, funding acquisition, validation, writing – review & editing; FZ and XD: formal analysis; FZ: visualization, writing – original draft; JC, LH, JS, JZ, YX, and LY: data curation. All authors commented on previous of the manuscripts. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Lu Yao or Yuntao Xie.

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The authors declare that they have no conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Ethical approval for this work was obtained from Ethics Committee of Peking University Cancer Hospital (No. 2011KT12).

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

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Zang, F., Ding, X., Chen, J. et al. Prevalence of BRCA1 and BRCA2 pathogenic variants in 8627 unselected patients with breast cancer: stratification of age at diagnosis, family history and molecular subtype. Breast Cancer Res Treat 195, 431–439 (2022). https://doi.org/10.1007/s10549-022-06702-4

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