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Morra, A.* ; Schreurs, M.A.C.* ; Andrulis, I.L.* ; Anton-Culver, H.* ; Augustinsson, A.* ; Beckmann, M.W.* ; Behrens, S.* ; Bojesen, S.E.* ; Bolla, M.K.* ; Brauch, H.* ; Broeks, A.* ; Buys, S.S.* ; Camp, N.J.* ; Castelao, J.E.* ; Cessna, M.H.* ; Chang-Claude, J.* ; Chung, W.K.* ; Colonna, S.V.* ; Couch, F.J.* ; Cox, A.* ; Cross, S.S.* ; Czene, K.* ; Daly, M.B.* ; Dennis, J.* ; Devilee, P.* ; Dörk, T.* ; Dunning, A.M.* ; Dwek, M.* ; Easton, D.F.* ; Eccles, D.M.* ; Eriksson, M.* ; Evans, D.G.* ; Fasching, P.A.* ; Fehm, T.N.* ; Figueroa, J.D.* ; Flyger, H.* ; Gabrielson, M.* ; Gago-Dominguez, M.* ; Garcia-Closas, M.* ; García-Sáenz, J.A.* ; Genkinger, J.* ; Grassmann, F.* ; Gündert, M. ; Hahnen, E.* ; Haiman, C.A.* ; Hamann, U.* ; Harrington, P.A.* ; Hartikainen, J.M.* ; Hoppe, R.* ; Hopper, J.L.* ; Houlston, R.S.* ; Howell, A.* ; Jakubowska, A.* ; Janni, W.* ; Jernström, H.* ; John, E.M.* ; Johnson, N.* ; Jones, M.E.* ; Kristensen, V.N.* ; Kurian, A.W.* ; Lambrechts, D.* ; Le Marchand, L.* ; Lindblom, A.* ; Lubinski, J.* ; Lux, M.P.* ; Mannermaa, A.* ; Mavroudis, D.* ; Mulligan, A.M.* ; Muranen, T.A.* ; Nevanlinna, H.* ; Nevelsteen, I.* ; Neven, P.* ; Newman, W.G.* ; Obi, N.* ; Offit, K.* ; Olshan, A.F.* ; Park-Simon, T.W.* ; Patel, A.V.* ; Peterlongo, P.* ; Phillips, K.A.* ; Plaseska-Karanfilska, D.* ; Polley, E.C.* ; Presneau, N.* ; Pylkäs, K.* ; Rack, B.* ; Radice, P.* ; Rashid, M.U.* ; Rhenius, V.* ; Robson, M.* ; Romero, A.* ; Saloustros, E.* ; Sawyer, E.J.* ; Schmutzler, R.K.* ; Schuetze, S.* ; Scott, C.* ; Shah, M.* ; Smichkoska, S.* ; Southey, M.C.* ; Tapper, W.J.* ; Teras, L.R.* ; Tollenaar, R.A.E.M.* ; Tomczyk, K.* ; Tomlinson, I.* ; Troester, M.A.* ; Vachon, C.M.* ; van Veen, E.M.* ; Wang, Q.* ; Wendt, C.* ; Wildiers, H.* ; Winqvist, R.* ; Ziogas, A.* ; Hall, P.* ; Pharoah, P.D.P.* ; Adank, M.A.* ; Hollestelle, A.* ; Schmidt, M.K.* ; Hooning, M.J.*

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

Cancer Med. 12, 16142-16162 (2023)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Chek2 C.1100delc Germline Genetic Variant ; Contralateral Breast Cancer Risk ; Radiotherapy ; Survival ; Systemic Treatment; Chek2-asterisk-1100delc; Mutation
ISSN (print) / ISBN 2045-7634
e-ISSN 2045-7634
Journal Cancer Medicine
Quellenangaben Volume: 12, Issue: 15, Pages: 16142-16162 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)
Grants Medical Research Council