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. 2025 Feb 18;24(1):23.
doi: 10.1007/s10689-025-00448-w.

CHEK2-related breast cancer: real-world challenges

Luiza N Weis  1 , Brittany L Bychkovsky  2   3   4   5 , Adela Rodríguez Hernandez  2   3   5   6   7 , Romualdo Barroso-Sousa  1 , Renata L Sandoval  8   9
Affiliations

CHEK2-related breast cancer: real-world challenges

Luiza N Weis et al. Fam Cancer. .

Abstract

Purpose: Management of cancer risks associated with the CHEK2 gene, a moderate penetrance breast cancer gene, is challenging in real-world practice. Family history, traditional breast cancer risk factors, and specific genetic CHEK2 variants are risk modifiers in this setting and add complexity for surveillance and risk-reduction decisions. Here, we present a case series of Brazilian CHEK2 carriers affected by breast cancer.

Methods: Patients evaluated in the Oncogenetics Department of Hospital Sírio-Libanês (Brasília, Brazil) between November 2017 and September 2021, who had a personal history of breast cancer and a germline genetic test with a pathogenic or likely pathogenic CHEK2 variant, were selected for case description. Clinical pearls and knowledge gaps were highlighted for each case.

Results: Twelve women were included in this descriptive analysis. All patients had early-stage breast cancer. Most of them were diagnosed with breast cancer prior to age 50 (9/12) and had a close relative affected by breast cancer (9/12). Seven patients harbored intronic pathogenic variants. Clinical pearls included the following: lack of risk estimates for intronic CHEK2 variants among non-European ancestry CHEK2 carriers, environmental exposures as a risk modifier, notable non-breast cancer diagnosis at young ages, incidental germline finding during tumor profiling, breast cancer diagnosis before the recommended age of breast cancer screening, family history of breast cancer as a risk modifier, and clinical outcomes after breast cancer treatment.

Conclusions: Improvements in cancer risk assessment and cancer prevention for CHEK2 carriers are still needed to overcome current clinical challenges on the management of these patients.

Keywords: CHEK2; Breast cancer; Moderate penetrance; Risk management.

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Conflict of interest statement

Declarations. Competing interests: LNW has received honoraria from Libbs, Novartis and Roche and travel accommodations or expenses from Libbs, GSK and Daiichi-Sankyo. Ethical approval: This study was approved by the Institutional Research Ethical Committee of the Hospital Sírio-Libanês (CAAE 21735619.3.0000.5461) and a waiver of informed consent was granted. All clinical and molecular data were de-identified before data sharing and analysis.

References

    1. NCCN Clinical practice guidelines in oncology. genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Version 3.2024. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf . Accessed on: March 27, 2024.
    1. Bedrosian I, Somerfield MR, Achatz MI et al (2024) Germline testing in patients with breast cancer: ASCO-society of surgical oncology guideline. J Clin Oncol 42:584–604. https://doi.org/10.1200/JCO.23.02225 - DOI - PubMed
    1. Breast Cancer Association Consortium, Dorling L, Carvalho S et al (2021) Breast cancer risk genes - association analysis in more than 113,000 women. N Engl J Med 384:428–439. https://doi.org/10.1056/NEJMoa1913948 - DOI
    1. Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358:1389–1399. https://doi.org/10.1016/S0140-6736(01)06524-2 - DOI
    1. Hu C, Hart SN, Gnanaolivu R et al (2021) A population-based study of genes previously implicated in breast cancer. N Engl J Med 384:440–451. https://doi.org/10.1056/NEJMoa2005936 - DOI - PubMed - PMC

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