BREAST CANCER: The prevalence of CHEK2 germline pathogenic variants was 2.3% in this 2,344 participant study; CHEK2 variants were associated with ER+ disease and worse overall survival
The prevalence of CHEK2 germline pathogenic variants was 2.3% in this 2,344 participant study; CHEK2 variants were associated with ER+ disease and worse overall survival.
Pathogenic Variants in CHEK2 Are Associated With an Adverse Prognosis in Symptomatic Early-Onset Breast Cancer
DOI: 10.1200/PO.19.00178 JCO Precision Oncology no. 4 (2020) 472-485. Published online May 4, 2020.
Checkpoint kinase 2 (CHEK2) is frequently included in multigene panels. We describe the associated outcomes among carriers of CHEK2 pathogenic variants in young patients with symptomatic breast cancer.
PATIENTS AND METHODS
Participants (N = 2,344) in the Prospective Outcomes in Sporadic Versus Hereditary Breast Cancer study had a diagnosis of primary invasive breast cancer at age ≤ 40 years. Summary statistics were used to compare tumor characteristics among CHEK2+ carriers with those who were CHEK2−. Kaplan-Meier curves were used to demonstrate overall survival (OS) and distant disease-free survival.
Overall, 53 of the 2,344 participants (2.3%) had a pathogenic CHEK2 variant. CHEK2+-associated tumors were significantly more likely to be grade 2, estrogen receptor and progesterone receptor–positive compared with CHEK2− tumors (grade 2, n = 28 of 52 [53.8%] v n = 803 of 2,229 [36.0%]; P = .029). CHEK2-associated tumors were significantly more likely to have nodal involvement (N1, n = 37 of 53 [69.8%] v 1,169 of 2,253 [51.9%]; P = .0098) and demonstrated a trend toward multifocality. A higher proportion of participants with CHEK2+ variants with invasive breast cancer were obese than were those with CHEK2− variant (28.3% v 18.8%; P = .039). Univariate and multivariable analyses revealed that OS and distant disease-free survival were significantly worse in CHEK2+ versus CHEK2− carriers (OS hazard ratio, 1.58; 95% CI, 1.01 to 2.48; P = .043).
This work highlights the adverse prognosis associated with breast cancer in carriers of CHEK2 pathogenic variants. It also identifies a potential association among obesity, family history, and breast cancer risk in young CHEK2 gene carriers.