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

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...

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Autores: 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 Fernández, José Esteban, Cessna, M.H., Chang-Claude, J., Chung, W.K., Sahlberg, K.K., Børresen-Dale, A.-L., Gram, I.T., Olsen, K.S., Engebråten, O., Naume, B., Geisler, J., Grenaker Alnæs, G.I., 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, Manuela, García-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., Clarke, C., Marsh, D., Scott, R., Baxter, R., Yip, D., Carpenter, J., Davis, A., Pathmanathan, N., Simpson, P., Graham, J.D., Sachchithananthan, M., Amor, D., Andrews, L., Antill, Y., Balleine, R., Beesley, J., Bennett, I., Bogwitz, M., Botes, L., Brennan, M., Brown, M., Buckley, M., Burke, J., Butow, P., Caldon, L., Campbell, I., Cao, M., Chakrabarti, A., Chauhan, D., Chauhan, M., Chenevix-Trench, G., Christian, A., Cohen, P., Colley, A., Crook, A., Cui, J., Courtney, E., Cummings, M., Dawson, S.-J., DeFazio, A., Delatycki, M., Dickson, R., Dixon, J., Edkins, T., Edwards, S., Farshid, G., Fellows, A., Fenton, G., Field, M., Flanagan, J., Fong, P., Forrest, L., Fox, S., French, J., Friedlander, M., Gaff, C., Gattas, M., George, P., Greening, S., Harris, M., Hart, S., Hayward, N., Hopper, J., Hoskins, C., Hunt, C., James, P., Jenkins, M., Kidd, A., Kirk, J., Koehler, J., Kollias, J., Lakhani, S., Lawrence, M., Lee, J., Li, S., Lindeman, G., Lipton, L., Lobb, L., Loi, S., Mann, G., McLachlan, S.A., Meiser, B., Milne, R., Nightingale, S., O'Connell, S., O'Sullivan, S., Ortega, D.G., Pachter, N., Pang, J.-M., Pathak, G., Patterson, B., Pearn, A., Phillips, K., Pieper, E., Ramus, S., Rickard, E., Robinson, B., Saleh, M., Skandarajah, A., Salisbury, E., Saunders, C., Saunus, J., Scott, C., Sexton, A., Shelling, A., Southey, M., Spurdle, A., Taylor, J., Taylor, R., Thorne, H., Trainer, A., Tucker, K., Visvader, J., Walker, L., Williams, R., Winship, I., Young, M.A., Zaheed, M., 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., Lubi?ski, 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., 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.
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Servizo Galego de Saúde (SERGAS)
Repositorio:RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:oai:runa.sergas.gal:20.500.11940/21123
Acceso en línea:https://portalcientifico.sergas.gal//documentos/65c35cbbd2edca1267d6a0f9
http://hdl.handle.net/20.500.11940/21123
Access Level:acceso abierto
Palabra clave:Female
Humans
Breast Neoplasms
Checkpoint Kinase 2
Genetic Predisposition to Disease
Germ-Line Mutation
Heterozygote
Proportional Hazards Models
AS Vigo
CHUVI
AS Santiago
IDIS
Descripción
Sumario: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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