Abstract P2-09-16: Clinicopatological features and outcome of breast cancer in CHEK2 germline mutation carriers
Authors: Schlosser Shir , Molho Rinat Bernstein , Karminsky Natalia , Barsuk Daphna , Goldberg Yael , Friedman Eitan , Yerushalmi Rinat , Drumea Keren , Kedar Inbal , Jiveliouk Irina , David Merav Akiva Ben 
Published: March 2022

Background: Carriers of CHEK2 germline mutations are at moderately increased (20-40%), lifetime risk for developing breast cancer (BC), in part depending on specific family history and mutation type and location. CHEK2 mutation associated BC is commonly associated with positive estrogen receptor(ER) tumor subtype, but other tumor features are less evident. Long term follow up and outcome of patients with CHEK2 -associated BC has not been reported. The clinical and tumoral features as well as and clinical outcome of a consecutive series of 57 BC patients (63 primary tumors) harboring pathogenic CHEK2 mutation is presented. Methods: Following IRB approval, hospital records from 3 major cancer centers in Israel were reviewed to identify female CHEK2 pathogenic/likely pathogenic sequence variant (P/LPSV) carriers who were diagnosed with BC between 2001-2021.Relevant clinical features, tumor data, treatment details and outcome were retrieved and. Mann-Whitney U-test was performed for continuous variables and descriptive statistics were used for non-continuous variables.Results:104 BC cases with documented CHEK2 sequence variant were obtained. 57 were carriers of CHEK2germline P/LPSV, and 63 primary tumors were diagnosed in these participants. Median age at diagnosis was 50 years (mean 51, range 31-73) and median follow up time of 23.5 months (mean 47,range 1-228). Six of 57 [10.5%] were diagnosed with synchronous bilateral tumors, and 6 [10.5%]with multifocal ipsilateral tumors. Twenty-three (41%) of the invasive tumors had positive regional lymph nodes at diagnosis and median tumor size was 1.2cm (mean 1.9, range 0.3-11.3cm). Seventy seven percent were invasive ducal carcinoma, 8% were invasive lobular, 11% DCIS, and two cases -unknown histology. Fifty-seven of 63 tumors (90%) were ER positive, and only two cases were triple negative. Ten (16%)tumors were HER2 positive. Most tumors (66%) were intermediate grade, 18% - low-grade, and 16%- high-grade tumors. Eighty percent opted for breast conserving surgery and 29 received chemotherapy, all were AC-T regimen, with anti HER2 agents in HER2 positive tumors. The most common PSV were c.1100delC (17 patients) and p.S428P (17 patients). Mean age at diagnosis for these two PSVs were 47 and 57 years, respectively (p=0.00438). Seven (12%) patients developed metastatic disease during the follow up period. Conclusion: This descriptive study shows some unique features of CHEK2 associated BC: early age at diagnosis(for the c.1100delC PSV) and high percentage of ER positivity. Synchronous and multifocal tumors were common. Further long term follow up and larger detailed description is warranted in this unique population.

Citation Format: Shir Schlosser, Rinat Bernstein Molho, Natalia Karminsky, Daphna Barsuk, Yael Goldberg, Eitan Friedman, Rinat Yerushalmi, Keren Drumea, Inbal Kedar, Irina Jiveliouk, Merav Akiva Ben David. Clinicopatological features and outcome of breast cancer in CHEK2 germline mutation carriers [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-16.