학술논문
Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival
Document Type
article
Author
Anna Morra; Maartje A. C. Schreurs; Irene L. Andrulis; Hoda Anton‐Culver; Annelie Augustinsson; Matthias W. Beckmann; Sabine Behrens; Stig E. Bojesen; Manjeet K. Bolla; Hiltrud Brauch; Annegien Broeks; Saundra S. Buys; Nicola J. Camp; Jose E. Castelao; Melissa H. Cessna; Jenny Chang‐Claude; Wendy K. Chung; NBCS Collaborators; Sarah V. Colonna; Fergus J. Couch; Angela Cox; Simon S. Cross; Kamila Czene; Mary B. Daly; Joe Dennis; Peter Devilee; Thilo Dörk; Alison M. Dunning; Miriam Dwek; Douglas F. Easton; Diana M. Eccles; Mikael Eriksson; D. Gareth Evans; Peter A. Fasching; Tanja N. Fehm; Jonine D. Figueroa; Henrik Flyger; Marike Gabrielson; Manuela Gago‐Dominguez; Montserrat García‐Closas; José A. García‐Sáenz; Jeanine Genkinger; Felix Grassmann; Melanie Gündert; Eric Hahnen; Christopher A. Haiman; Ute Hamann; Patricia A. Harrington; Jaana M. Hartikainen; Reiner Hoppe; John L. Hopper; Richard S. Houlston; Anthony Howell; ABCTB Investigators; kConFab Investigators; Anna Jakubowska; Wolfgang Janni; Helena Jernström; Esther M. John; Nichola Johnson; Michael E. Jones; Vessela N. Kristensen; Allison W. Kurian; Diether Lambrechts; Loic Le Marchand; Annika Lindblom; Jan Lubiński; Michael P. Lux; Arto Mannermaa; Dimitrios Mavroudis; Anna Marie Mulligan; Taru A. Muranen; Heli Nevanlinna; Ines Nevelsteen; Patrick Neven; William G. Newman; Nadia Obi; Kenneth Offit; Andrew F. Olshan; Tjoung‐Won Park‐Simon; Alpa V. Patel; Paolo Peterlongo; Kelly‐Anne Phillips; Dijana Plaseska‐Karanfilska; Eric C. Polley; Nadege Presneau; Katri Pylkäs; Brigitte Rack; Paolo Radice; Muhammad U. Rashid; Valerie Rhenius; Mark Robson; Atocha Romero; Emmanouil Saloustros; Elinor J. Sawyer; Rita K. Schmutzler; Sabine Schuetze; Christopher Scott; Mitul Shah; Snezhana Smichkoska; Melissa C. Southey; William J. Tapper; Lauren R. Teras; Rob A. E. M. Tollenaar; Katarzyna Tomczyk; Ian Tomlinson; Melissa A. Troester; Celine M. Vachon; Elke M. vanVeen; Qin Wang; Camilla Wendt; Hans Wildiers; Robert Winqvist; Argyrios Ziogas; Per Hall; Paul D. P. Pharoah; Muriel A. Adank; Antoinette Hollestelle; Marjanka K. Schmidt; Maartje J. Hooning
Source
Cancer Medicine, Vol 12, Iss 15, Pp 16142-16162 (2023)
Subject
Language
English
ISSN
2045-7634
Abstract
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.