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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 LU ; Beckmann, Matthias W ; Behrens, Sabine ; Bojesen, Stig E ; Bolla, Manjeet K and Brauch, Hiltrud , et al. (2023) In Cancer Medicine 12(15). p.16142-16162
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,... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Female, Humans, Breast Neoplasms/genetics, Checkpoint Kinase 2/genetics, Genetic Predisposition to Disease, Germ-Line Mutation, Heterozygote, Proportional Hazards Models
in
Cancer Medicine
volume
12
issue
15
pages
16142 - 16162
publisher
Wiley-Blackwell
external identifiers
  • pmid:37401034
ISSN
2045-7634
DOI
10.1002/cam4.6272
language
English
LU publication?
yes
additional info
© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
id
b40d5795-0444-4485-a719-d5cd3d11e21f
date added to LUP
2023-11-11 15:56:00
date last changed
2023-11-13 08:44:54
@article{b40d5795-0444-4485-a719-d5cd3d11e21f,
  abstract     = {{<p>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.</p><p>AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.</p><p>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.</p><p>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)].</p><p>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.</p>}},
  author       = {{Morra, Anna and Schreurs, Maartje A C and Andrulis, Irene L and Anton-Culver, Hoda and Augustinsson, Annelie and Beckmann, Matthias W and Behrens, Sabine and Bojesen, Stig E and Bolla, Manjeet K and Brauch, Hiltrud and Broeks, Annegien and Buys, Saundra S and Camp, Nicola J and Castelao, Jose E and Cessna, Melissa H and Chang-Claude, Jenny and Chung, Wendy K and Colonna, Sarah V and Couch, Fergus J and Cox, Angela and Cross, Simon S and Czene, Kamila and Daly, Mary B and Dennis, Joe and Devilee, Peter and Dörk, Thilo and Dunning, Alison M and Dwek, Miriam and Easton, Douglas F and Eccles, Diana M and Eriksson, Mikael and Evans, D Gareth and Fasching, Peter A and Fehm, Tanja N and Figueroa, Jonine D and Flyger, Henrik and Gabrielson, Marike and Gago-Dominguez, Manuela and García-Closas, Montserrat and García-Sáenz, José A and Genkinger, Jeanine and Grassmann, Felix and Gündert, Melanie and Hahnen, Eric and Haiman, Christopher A and Hamann, Ute and Harrington, Patricia A and Hartikainen, Jaana M and Jernström, Helena}},
  issn         = {{2045-7634}},
  keywords     = {{Female; Humans; Breast Neoplasms/genetics; Checkpoint Kinase 2/genetics; Genetic Predisposition to Disease; Germ-Line Mutation; Heterozygote; Proportional Hazards Models}},
  language     = {{eng}},
  number       = {{15}},
  pages        = {{16142--16162}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Cancer Medicine}},
  title        = {{Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival}},
  url          = {{http://dx.doi.org/10.1002/cam4.6272}},
  doi          = {{10.1002/cam4.6272}},
  volume       = {{12}},
  year         = {{2023}},
}