Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
- Author(s)
- 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; Dork, 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; Garcia-Closas, M; Garcia-Saenz, JA; Genkinger, J; Grassmann, F; Gundert, 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; Jernstrom, H; John, EM; Johnson, N; Jones, ME; Kristensen, VN; Kurian, AW; Lambrechts, D; Le Marchand, L; Lindblom, A; Lubinski, 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, TW; Patel, AV; Peterlongo, P; Phillips, KA; Plaseska-Karanfilska, D; Polley, EC; Presneau, N; Pylkas, 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;
- Details
- Publication Year 2023-08,Volume 12,Issue #15,Page 16142-16162
- Journal Title
- Cancer Medicine
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- Wiley
- Keywords
- Female; Humans; *Breast Neoplasms/genetics/radiotherapy; Checkpoint Kinase 2/genetics; Genetic Predisposition to Disease; Germ-Line Mutation; Heterozygote; Proportional Hazards Models; CHEK2 c.1100delC germline genetic variant; contralateral breast cancer risk; radiotherapy; survival; systemic treatment
- Department(s)
- Laboratory Research; Medical Oncology
- PubMed ID
- 37401034
- Publisher's Version
- https://doi.org/10.1002/cam4.6272
- Open Access at Publisher's Site
https://doi.org/10.1002/cam4.6272- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-11-08 07:27:51
Last Modified: 2023-11-08 07:28:27