Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
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; ,; 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; Le Marchand, Loic; 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 (2023-08-31)
John Wiley & Sons
31.08.2023
Morra A, Schreurs MAC, Andrulis IL, et al. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Med. 2023; 12: 16142-16162. doi:10.1002/cam4.6272
https://creativecommons.org/licenses/by/4.0/
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202401291485
https://urn.fi/URN:NBN:fi:oulu-202401291485
Tiivistelmä
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.
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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