CHEK2-related breast cancer: real-world challenges.

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.