Sensitivity to Systemic Therapy for Metastatic Breast Cancer in CHEK2 1100delC Mutation Carriers

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2015 May 11

PMID 25958056

Citations 10

Authors

Mieke Kriege

Agnes Jager

Antoinette Hollestelle

Els M J J Berns

Jannet Blom

Marion E Meijer-Van Gelder

Anieta M Sieuwerts

Ans van den Ouweland

J Margriet Collee

Judith R Kroep

John W M Martens

Maartje J Hooning

Caroline Seynaeve

Affiliations

Soon will be listed here.

Abstract

Purpose: The role of CHEK2 in DNA repair by homologous recombination suggests that CHEK2-associated breast cancer (BC) patients might be more sensitive to chemotherapy inducing double-strand DNA breaks, but results hereon are lacking. We compared the sensitivity to first-line chemotherapy and endocrine therapy between CHEK2 1100delC and non-CHEK2 metastatic breast cancer (MBC) patients.

Methods: Sixty-two CHEK2 1100delC MBC patients were selected from three cohorts genotyped for CHEK2 1100delC (one non-BRCA1/2 cohort and two sporadic cohorts). Controls were 62 non-CHEK2 MBC patients, matched for age at and year of primary BC diagnosis, and year of metastatic disease. Objective response rate (complete and partial response) to, and progression-free survival (PFS) and overall survival (OS) after start of first-line chemotherapy and endocrine therapy were compared between CHEK2 and non-CHEK2 patients.

Results: Median age at BC diagnosis was 46 and 51 years at MBC diagnosis. First-line chemotherapy consisted of anthracycline-based chemotherapy (n = 73), taxanes (n = 16), CMF(-like) chemotherapy (n = 33) and taxane/anthracycline regimens (n = 2). CHEK2 and non-CHEK2 patients had a comparable objective response rate (44 vs. 52 %). Also, PFS and OS after start of chemotherapy were comparable between both patient groups (hazard ratio 0.91; 95 % confidence interval 0.63-1.30 and 1.03; 95 % CI 0.71-1.49, respectively). Thirty-six CHEK2 and 32 non-CHEK2 patients received first-line endocrine therapy (mainly tamoxifen) for MBC. No significant differences were observed in objective response rate to, and PFS and OS after start of endocrine therapy.

Conclusion: No differential efficacy of chemotherapy and endocrine therapy given for MBC was observed in CHEK2 versus non-CHEK2 patients.

Citing Articles

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.

Morra A, Schreurs M, Andrulis I, Anton-Culver H, Augustinsson A, Beckmann M Cancer Med. 2023; 12(15):16142-16162.

PMID: 37401034 PMC: 10469654. DOI: 10.1002/cam4.6272.

Breast cancer genomes from CHEK2 c.1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile.

Smid M, Schmidt M, Prager-van der Smissen W, Ruigrok-Ritstier K, Schreurs M, Cornelissen S Breast Cancer Res. 2023; 25(1):53.

PMID: 37161532 PMC: 10169359. DOI: 10.1186/s13058-023-01653-0.

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.

Morra A, Schreurs M, Andrulis I, Anton-Culver H, Augustinsson A, Beckmann M Res Sq. 2023; .

PMID: 36824750 PMC: 9949248. DOI: 10.21203/rs.3.rs-2569372/v1.

Functions of Breast Cancer Predisposition Genes: Implications for Clinical Management.

Yoshimura A, Imoto I, Iwata H Int J Mol Sci. 2022; 23(13).

PMID: 35806485 PMC: 9267387. DOI: 10.3390/ijms23137481.

Comparison of Patient Susceptibility Genes Across Breast Cancer: Implications for Prognosis and Therapeutic Outcomes.

Peleg Hasson S, Menes T, Sonnenblick A Pharmgenomics Pers Med. 2020; 13:227-238.

PMID: 32801835 PMC: 7394592. DOI: 10.2147/PGPM.S233485.

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