Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival.
CHEK2 c.1100delC germline genetic variant
contralateral breast cancer risk
radiotherapy
survival
systemic treatment
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
30
04
2023
received:
21
02
2023
accepted:
03
06
2023
medline:
1
9
2023
pubmed:
4
7
2023
entrez:
4
7
2023
Statut:
ppublish
Résumé
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. To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. 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. 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)]. 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.
Sections du résumé
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.
Identifiants
pubmed: 37401034
doi: 10.1002/cam4.6272
pmc: PMC10469654
doi:
Substances chimiques
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
16142-16162Subventions
Organisme : NCI NIH HHS
ID : UM1 CA164917
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA163353
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA058860
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201800015I
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA192393
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA042014
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186107
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA098758
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA063464
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148112
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201800032I
Pays : United States
Organisme : CDC HHS
ID : NU58DP006320
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA047147
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA058223
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA132839
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA177150
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA097396
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA069664
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201800016I
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201800009I
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA176726
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA054281
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 CP010119
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : NCCDPHP CDC HHS
ID : NU58DP006344
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148065
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA116201
Pays : United States
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z01 ES049030
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA176785
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA047305
Pays : United States
Organisme : NCI NIH HHS
ID : K07 CA092044
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA087969
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA156733
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA253187
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA077398
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA164920
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA176726
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA199277
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA164920
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA179715
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140286
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA116167
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148537
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA128931
Pays : United States
Investigateurs
Kristine K Sahlberg
(KK)
Anne-Lise Børresen-Dale
(AL)
Inger Torhild Gram
(IT)
Karina Standahl Olsen
(KS)
Olav Engebråten
(O)
Bjørn Naume
(B)
Jürgen Geisler
(J)
Grethe I Grenaker Alnaes
(GI)
Christine Clarke
(C)
Deborah Marsh
(D)
Rodney Scott
(R)
Robert Baxter
(R)
Desmond Yip
(D)
Jane Carpenter
(J)
Alison Davis
(A)
Nirmala Pathmanathan
(N)
Peter Simpson
(P)
J Dinny Graham
(JD)
Mythily Sachchithananthan
(M)
David Amor
(D)
Lesley Andrews
(L)
Yoland Antill
(Y)
Rosemary Balleine
(R)
Jonathan Beesley
(J)
Ian Bennett
(I)
Michael Bogwitz
(M)
Leon Botes
(L)
Meagan Brennan
(M)
Melissa Brown
(M)
Michael Buckley
(M)
Jo Burke
(J)
Phyllis Butow
(P)
Liz Caldon
(L)
Ian Campbell
(I)
Michelle Cao
(M)
Anannya Chakrabarti
(A)
Deepa Chauhan
(D)
Manisha Chauhan
(M)
Georgia Chenevix-Trench
(G)
Alice Christian
(A)
Paul Cohen
(P)
Alison Colley
(A)
Ashley Crook
(A)
James Cui
(J)
Eliza Courtney
(E)
Margaret Cummings
(M)
Sarah-Jane Dawson
(SJ)
Anna DeFazio
(A)
Martin Delatycki
(M)
Rebecca Dickson
(R)
Joanne Dixon
(J)
Ted Edkins
(T)
Stacey Edwards
(S)
Gelareh Farshid
(G)
Andrew Fellows
(A)
Georgina Fenton
(G)
Michael Field
(M)
James Flanagan
(J)
Peter Fong
(P)
Laura Forrest
(L)
Stephen Fox
(S)
Juliet French
(J)
Michael Friedlander
(M)
Clara Gaff
(C)
Mike Gattas
(M)
Peter George
(P)
Sian Greening
(S)
Marion Harris
(M)
Stewart Hart
(S)
Nick Hayward
(N)
John Hopper
(J)
Cass Hoskins
(C)
Clare Hunt
(C)
Paul James
(P)
Mark Jenkins
(M)
Alexa Kidd
(A)
Judy Kirk
(J)
Jessica Koehler
(J)
James Kollias
(J)
Sunil Lakhani
(S)
Mitchell Lawrence
(M)
Jason Lee
(J)
Shuai Li
(S)
Geoff Lindeman
(G)
Lara Lipton
(L)
Liz Lobb
(L)
Sherene Loi
(S)
Graham Mann
(G)
Deborah Marsh
(D)
Sue Anne McLachlan
(SA)
Bettina Meiser
(B)
Roger Milne
(R)
Sophie Nightingale
(S)
Shona O'Connell
(S)
Sarah O'Sullivan
(S)
David Gallego Ortega
(DG)
Nick Pachter
(N)
Jia-Min Pang
(JM)
Gargi Pathak
(G)
Briony Patterson
(B)
Amy Pearn
(A)
Kelly Phillips
(K)
Ellen Pieper
(E)
Susan Ramus
(S)
Edwina Rickard
(E)
Bridget Robinson
(B)
Mona Saleh
(M)
Anita Skandarajah
(A)
Elizabeth Salisbury
(E)
Christobel Saunders
(C)
Jodi Saunus
(J)
Rodney Scott
(R)
Clare Scott
(C)
Adrienne Sexton
(A)
Andrew Shelling
(A)
Peter Simpson
(P)
Melissa Southey
(M)
Amanda Spurdle
(A)
Jessica Taylor
(J)
Renea Taylor
(R)
Heather Thorne
(H)
Alison Trainer
(A)
Kathy Tucker
(K)
Jane Visvader
(J)
Logan Walker
(L)
Rachael Williams
(R)
Ingrid Winship
(I)
Mary Ann Young
(MA)
Milita Zaheed
(M)
Informations de copyright
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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