Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.
Date
2023-08-01Author
Morra, A
Schreurs, MAC
Andrulis, IL
Anton-Culver, H
Augustinsson, A
Beckmann, MW
Behrens, S
Bojesen, SE
Bolla, MK
Brauch, H
Broeks, A
Buys, SS
Camp, NJ
Castelao, JE
Cessna, MH
Chang-Claude, J
Chung, WK
NBCS Collaborators,
Colonna, SV
Couch, FJ
Cox, A
Cross, SS
Czene, K
Daly, MB
Dennis, J
Devilee, P
Dörk, T
Dunning, AM
Dwek, M
Easton, DF
Eccles, DM
Eriksson, M
Evans, DG
Fasching, PA
Fehm, TN
Figueroa, JD
Flyger, H
Gabrielson, M
Gago-Dominguez, M
García-Closas, M
García-Sáenz, JA
Genkinger, J
Grassmann, F
Gündert, M
Hahnen, E
Haiman, CA
Hamann, U
Harrington, PA
Hartikainen, JM
Hoppe, R
Hopper, JL
Houlston, RS
Howell, A
ABCTB Investigators,
kConFab Investigators,
Jakubowska, A
Janni, W
Jernström, H
John, EM
Johnson, N
Jones, ME
Kristensen, VN
Kurian, AW
Lambrechts, D
Le Marchand, L
Lindblom, A
Lubiński, J
Lux, MP
Mannermaa, A
Mavroudis, D
Mulligan, AM
Muranen, TA
Nevanlinna, H
Nevelsteen, I
Neven, P
Newman, WG
Obi, N
Offit, K
Olshan, AF
Park-Simon, T-W
Patel, AV
Peterlongo, P
Phillips, K-A
Plaseska-Karanfilska, D
Polley, EC
Presneau, N
Pylkäs, K
Rack, B
Radice, P
Rashid, MU
Rhenius, V
Robson, M
Romero, A
Saloustros, E
Sawyer, EJ
Schmutzler, RK
Schuetze, S
Scott, C
Shah, M
Smichkoska, S
Southey, MC
Tapper, WJ
Teras, LR
Tollenaar, RAEM
Tomczyk, K
Tomlinson, I
Troester, MA
Vachon, CM
van Veen, EM
Wang, Q
Wendt, C
Wildiers, H
Winqvist, R
Ziogas, A
Hall, P
Pharoah, PDP
Adank, MA
Hollestelle, A
Schmidt, MK
Hooning, MJ
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. METHODS: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. RESULTS: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. CONCLUSION: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
Collections
Subject
Science & Technology
Life Sciences & Biomedicine
Oncology
CHEK2 c.1100delC germline genetic variant
contralateral breast cancer risk
radiotherapy
survival
systemic treatment
CHEK2-ASTERISK-1100DELC
MUTATION
Research team
Integrative Cancer Epidem
Cancer Genomics
Language
eng
Date accepted
2023-06-03
License start date
2023-08-01
Citation
Cancer Medicine, 2023, 12 (15),
Publisher
WILEY