Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

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; 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; Helena Jernström; NBCS Collaborators

doi:10.1002/cam4.6272

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

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, Sarah V Colonna, Fergus J Couch, Angela CoxSimon 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, Helena Jernström, NBCS Collaborators

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

Sammanfattning

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.

Originalspråk	engelska
Sidor (från-till)	16142-16162
Tidskrift	Cancer Medicine
Volym	12
Nummer	15
DOI	https://doi.org/10.1002/cam4.6272
Status	Published - 2023 aug.

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Cancer och onkologi

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Morra, A., Schreurs, M. A. C., Andrulis, I. L., Anton-Culver, H., Augustinsson, A., Beckmann, M. W., Behrens, S., Bojesen, S. E., Bolla, M. K., Brauch, H., Broeks, A., Buys, S. S., Camp, N. J., Castelao, J. E., Cessna, M. H., Chang-Claude, J., Chung, W. K., Colonna, S. V., Couch, F. J., ... NBCS Collaborators (2023). Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival. Cancer Medicine, 12(15), 16142-16162. https://doi.org/10.1002/cam4.6272

@article{b40d579504444485a719d5cd3d11e21f,

title = "Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival",

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.",

keywords = "Female, Humans, Breast Neoplasms/genetics, Checkpoint Kinase 2/genetics, Genetic Predisposition to Disease, Germ-Line Mutation, Heterozygote, Proportional Hazards Models",

author = "Anna Morra and Schreurs, {Maartje A C} and Andrulis, {Irene L} and Hoda Anton-Culver and Annelie Augustinsson and Beckmann, {Matthias W} and Sabine Behrens and Bojesen, {Stig E} and Bolla, {Manjeet K} and Hiltrud Brauch and Annegien Broeks and Buys, {Saundra S} and Camp, {Nicola J} and Castelao, {Jose E} and Cessna, {Melissa H} and Jenny Chang-Claude and Chung, {Wendy K} and Colonna, {Sarah V} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Daly, {Mary B} and Joe Dennis and Peter Devilee and Thilo D{\"o}rk and Dunning, {Alison M} and Miriam Dwek and Easton, {Douglas F} and Eccles, {Diana M} and Mikael Eriksson and Evans, {D Gareth} and Fasching, {Peter A} and Fehm, {Tanja N} and Figueroa, {Jonine D} and Henrik Flyger and Marike Gabrielson and Manuela Gago-Dominguez and Montserrat Garc{\'i}a-Closas and Garc{\'i}a-S{\'a}enz, {Jos{\'e} A} and Jeanine Genkinger and Felix Grassmann and Melanie G{\"u}ndert and Eric Hahnen and Haiman, {Christopher A} and Ute Hamann and Harrington, {Patricia A} and Hartikainen, {Jaana M} and Helena Jernstr{\"o}m and {NBCS Collaborators}",

note = "{\textcopyright} 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",

year = "2023",

month = aug,

doi = "10.1002/cam4.6272",

language = "English",

volume = "12",

pages = "16142--16162",

journal = "Cancer Medicine",

issn = "2045-7634",

publisher = "Wiley-Blackwell",

number = "15",

}

Morra, A, Schreurs, MAC, Andrulis, IL, Anton-Culver, H, Augustinsson, A, Beckmann, MW, Behrens, S, Bojesen, SE, Bolla, MK, Brauch, H, Broeks, A, Buys, SS, Camp, NJ, Castelao, JE, Cessna, MH, Chang-Claude, J, Chung, WK, Colonna, SV, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Dennis, J, Devilee, P, Dörk, T, Dunning, AM, Dwek, M, Easton, DF, Eccles, DM, Eriksson, M, Evans, DG, Fasching, PA, Fehm, TN, Figueroa, JD, Flyger, H, Gabrielson, M, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, Genkinger, J, Grassmann, F, Gündert, M, Hahnen, E, Haiman, CA, Hamann, U, Harrington, PA, Hartikainen, JM, Jernström, H & NBCS Collaborators 2023, 'Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival', Cancer Medicine, vol. 12, nr. 15, s. 16142-16162. https://doi.org/10.1002/cam4.6272

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 - 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 - 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

AU - Gündert, Melanie

AU - Hahnen, Eric

AU - Haiman, Christopher A

AU - Hamann, Ute

AU - Harrington, Patricia A

AU - Hartikainen, Jaana M

AU - Jernström, Helena

AU - NBCS Collaborators

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 - Female

KW - Humans

KW - Breast Neoplasms/genetics

KW - Checkpoint Kinase 2/genetics

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Heterozygote

KW - Proportional Hazards Models

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 -

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

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