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Frequency of germline pathogenic variants in breast cancer predisposition genes among young Turkish breast cancer patients

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Abstract

Purpose

One of the most important risk factors for hereditary breast and ovarian cancer is young age. We aim to report the frequency of pathogenic/likely pathogenic variants in breast cancer predisposing genes in young (≤ 40 years old) breast cancer patients who undergone 26-gene inherited cancer panel at our Breast Health Center.

Methods

Medical records of breast cancer patients who were referred to genetic counseling based on NCCN criteria and were ≤ 40 years of age are reviewed. The frequency of germline pathogenic/likely pathogenic variants who undergone 26-gene inherited cancer panel was analyzed.

Results

Among 414 breast cancer patients who were ≤ 40 years of age, 308 undergone 26-gene inherited cancer panel and 108 had next generation sequencing (NGS)-based BRCA 1 and 2 genetic testing. Median age was 35 (22–40), Family history in first degree relatives was present in 14% of patients. Forty-five percent of patients met one of the NCCN criteria for genetic testing, 41% of them met two criteria, and 14% of patients fulfilled ≥ 3 criteria. Seventy pathogenic/likely pathogenic variants (PV/LPV) were found in 65 (21%) patients. PV/LPs in BRCA genes and non-BRCA genes represented 53% and 44% of all PV/LPVs, accounting for 12% and 10% of patients in the study cohort respectively. Two PVs were present in 5 patients and eleven PVs were novel. The most common PVs were in BRCA 1 (n:18), BRCA 2 (n:19), ATM (n:7), CHEK2 (n:7) and TP53 (n:5) genes. Thirty-one percent of the patients with triple-negative tumors and 25% of the patients with hormone receptor-positive tumors had PV/LPVs with panel testing. Family history in first degree relatives (p = 0.029), the number of met NCCN criteria (p = 0.036) and axillary nodal involvement (p = 0.000) were more common in patients with PVs. When combined with patient group (n:106) who had only BRCA1 and 2 gene testing, 16% of Turkish breast cancer patients ≤ 40 years of age had PVs in BRCA genes.

Conclusion

One fifth of Turkish breast cancer patients ≤ 40 years of age had at least one PV/LPV in breast cancer predisposing genes with 26-gene inherited cancer panel. The frequency of PV/LPVs was higher in triple-negative young-onset patients compared to hormone receptor and Her-2 positive subtypes. Our findings regarding to frequency PV/LPVs in BRCA 1/2 and non-BRCA genes in young-onset breast cancer patients are in line with the literature.

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Data availability

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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Acknowledgements

The authors would like thank our physician assistant Aslınur Moral and nurse practitioner Beren Buyukcolak for their support in the collection of data.

Funding

This retrospective study did not need funding.

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Authors and Affiliations

  1. Department of Internal Medicine, Acibadem Altunizade Hospital, Altunizade District, Yurtcan St. No: 1, Uskudar, Istanbul, Turkey

    Aysun Dauti Isiklar

  2. Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Halkali Merkez, Turgut Ozal Bulvari No: 16, 34303, Kucukcekmece, Istanbul, Turkey

    Lamiya Aliyeva

  3. Acibadem Labgen Genetic Diagnosis Center, İçerenköy Kerem Aydınlar Campus, Kayışdağı Cd. No: 32, Atasehir, Istanbul, Turkey

    Ahmet Yesilyurt

  4. Department of General Surgery, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Altunizade District, Yurtcan St. No: 1, Uskudar, Istanbul, Turkey

    Aykut Soyder

  5. Department of Internal Medicine and Medical Oncology, Acibadem Mehmet Ali Aydinlar University, School of Medicine, Altunizade District, Yurtcan St. No: 1, Uskudar, Istanbul, Turkey

    Gul Basaran

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  1. Aysun Dauti Isiklar
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Contributions

Material preparation, data collection, and analysis were performed by (AI). The first draft of the manuscript was written by (AI; GB) and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Aysun Dauti Isiklar.

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Ethical approval of this retrospective study was granted in 2020 by (our university) Ethics Committee (Approval # 01.09.2020/754).

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Isiklar, A.D., Aliyeva, L., Yesilyurt, A. et al. Frequency of germline pathogenic variants in breast cancer predisposition genes among young Turkish breast cancer patients. Breast Cancer Res Treat 202, 297–304 (2023). https://doi.org/10.1007/s10549-023-07074-z

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