1. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival
- Author
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Morra, Anna, Schreurs, Maartje AC, Andrulis, Irene L, Anton‐Culver, Hoda, Augustinsson, Annelie, Beckmann, Matthias W, Behrens, Sabine, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Broeks, Annegien, Buys, Saundra S, Camp, Nicola J, Castelao, Jose E, Cessna, Melissa H, Chang‐Claude, Jenny, Chung, Wendy K, Sahlberg, Kristine K, Børresen‐Dale, Anne‐Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Alnæs, Grethe I Grenaker, Colonna, Sarah V, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fehm, Tanja N, Figueroa, Jonine D, Flyger, Henrik, Gabrielson, Marike, Gago‐Dominguez, Manuela, García‐Closas, Montserrat, García‐Sáenz, José A, Genkinger, Jeanine, Grassmann, Felix, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Hamann, Ute, Harrington, Patricia A, Hartikainen, Jaana M, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Clarke, Christine, Marsh, Deborah, Scott, Rodney, Baxter, Robert, Yip, Desmond, Carpenter, Jane, Davis, Alison, Pathmanathan, Nirmala, Simpson, Peter, Graham, J Dinny, Sachchithananthan, Mythily, Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Chenevix‐Trench, Georgia, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, and Dawson, Sarah‐Jane
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Women's Health ,Breast Cancer ,Clinical Research ,Prevention ,Cancer ,Female ,Humans ,Breast Neoplasms ,Checkpoint Kinase 2 ,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 ,NBCS Collaborators ,ABCTB Investigators ,kConFab Investigators ,Biochemistry and Cell Biology ,Oncology and carcinogenesis - Abstract
BackgroundBreast 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.AimTo assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.MethodsAnalyses 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.ResultsThere 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)].ConclusionSystemic 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.
- Published
- 2023