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Morra, Anna; Schreurs, Maartje A. C.; Andrulis, Irene L.; Anton-Culver, Hoda; Augustinsson, Annelie; Beckmann, Matthias W.; Behrens, Sabine; Bojesen, Stig E.; Bolla, Manjeet K.; & Brauch, Hiltrud, et al. (Preprint). Association of the CHEK2 C.1100DELC Variant, Radiotherapy, and Systemic Treatment with Contralateral Breast Cancer Risk and Breast Cancer-Specific Survival. Research Square. PMCID: PMC9949248


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. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of 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. 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)]. In 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. (Main MS: 3201 words).


Reference Type

Journal Article

Year Published


Journal Title

Research Square


Morra, Anna
Schreurs, Maartje A. C.
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.
Collaborators, Nbcs
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
Jakubowska, Anna
Janni, Wolfgang
Jernström, Helena
John, Esther M.
Johnson, Nichola
Jones, Michael E.
Kristensen, Vessela N.
Kurian, Allison W.
Lambrechts, Diether
Marchand, Loic Le
Lindblom, Annika
Lubiński, Jan
Lux, Michael P.
Mannermaa, Arto
Mavroudis, Dimitrios
Mulligan, Anna Marie
Muranen, Taru A.
Nevanlinna, Heli
Nevelsteen, Ines
Neven, Patrick
Newman, William G.
Obi, Nadia
Offit, Kenneth
Olshan, Andrew F.
Park-Simon, Tjoung-Won
Patel, Alpa V.
Peterlongo, Paolo
Phillips, Kelly-Anne
Plaseska-Karanfilska, Dijana
Polley, Eric C.
Presneau, Nadege
Pylkäs, Katri
Rack, Brigitte
Radice, Paolo
Rashid, Muhammad U.
Rhenius, Valerie
Robson, Mark
Romero, Atocha
Saloustros, Emmanouil
Sawyer, Elinor J.
Schmutzler, Rita K.
Schuetze, Sabine
Scott, Christopher
Shah, Mitul
Smichkoska, Snezhana
Southey, Melissa C.
Tapper, William J.
Teras, Lauren R.
Tollenaar, Rob A. E. M.
Tomczyk, Katarzyna
Tomlinson, Ian
Troester, Melissa A.
Vachon, Celine M.
van Veen, Elke M.
Wang, Qin
Wendt, Camilla
Wildiers, Hans
Winqvist, Robert
Ziogas, Argyrios
Hall, Per
Pharoah, Paul D. P.
Adank, Muriel A.
Hollestelle, Antoinette
Schmidt, Marjanka K.
Hooning, Maartje J.

Article Type




Data Set/Study

Breast Cancer Association Consortium (BCAC)




European Ancestry




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