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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chek2 C.1100delc Germline Genetic Variant ; Contralateral Breast Cancer Risk ; Radiotherapy ; Survival ; Systemic Treatment; Chek2-asterisk-1100delc; Mutation
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2045-7634
e-ISSN 2045-7634
Zeitschrift Cancer Medicine
Quellenangaben Band: 12, Heft: 15, Seiten: 16142-16162 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken, NJ
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research (IDF)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502100-001
Förderungen Medical Research Council
DOI 10.1002/cam4.6272
WOS ID 001023913600001
Scopus ID 85182821176
PubMed ID 37401034
Erfassungsdatum 2023-11-28
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