TY - JOUR
T1 - Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - ABCTB Investigators
AU - KConFab Investigators
AU - KConFab Investigators
AU - OSBREAC
AU - Morra, Anna
AU - Schreurs, Maartje A.C.
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Augustinsson, Annelie
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Brauch, Hiltrud
AU - Broeks, Annegien
AU - Buys, Saundra S.
AU - Camp, Nicola J.
AU - Castelao, Jose E.
AU - Cessna, Melissa H.
AU - Chang-Claude, Jenny
AU - Chung, Wendy K.
AU - Sahlberg, Kristine K.
AU - Børresen-Dale, Anne Lise
AU - Gram, Inger Torhild
AU - Olsen, Karina Standahl
AU - Engebråten, Olav
AU - Naume, Bjørn
AU - Geisler, Jürgen
AU - Grenaker Alnæs, Grethe I.
AU - Colonna, Sarah V.
AU - Couch, Fergus J.
AU - Cox, Angela
AU - Cross, Simon S.
AU - Czene, Kamila
AU - Daly, Mary B.
AU - Dennis, Joe
AU - Devilee, Peter
AU - Dörk, Thilo
AU - Dunning, Alison M.
AU - Dwek, Miriam
AU - Easton, Douglas F.
AU - Eccles, Diana M.
AU - Eriksson, Mikael
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Fehm, Tanja N.
AU - Figueroa, Jonine D.
AU - Flyger, Henrik
AU - Gabrielson, Marike
AU - Gago-Dominguez, Manuela
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Genkinger, Jeanine
AU - Grassmann, Felix
N1 - © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - Breast Neoplasms/genetics
KW - Checkpoint Kinase 2/genetics
KW - Female
KW - Genetic Predisposition to Disease
KW - Germ-Line Mutation
KW - Heterozygote
KW - Humans
KW - Proportional Hazards Models
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:001023913600001&DestLinkType=FullRecord&DestApp=WOS
UR - https://www.scopus.com/pages/publications/85182821176
U2 - 10.1002/cam4.6272
DO - 10.1002/cam4.6272
M3 - Article
C2 - 37401034
SN - 2045-7634
VL - 12
SP - 16142
EP - 16162
JO - Cancer Medicine
JF - Cancer Medicine
IS - 15
ER -
SDG 3 Good Health and Well-being