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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Cancer Medicine |
| Vol/bind | 12 |
| Udgave nummer | 15 |
| Sider (fra-til) | 16142-16162 |
| Antal sider | 21 |
| ISSN | 2045-7634 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Publisher Copyright:© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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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; Beckmann, Matthias W.; Behrens, Sabine; Bojesen, Stig E.; Bolla, Manjeet K.; Brauch, Hiltrud; Broeks, Annegien; Buys, Saundra S.; Camp, Nicola J.; Castelao, Jose E.; Cessna, Melissa H.; Chang-Claude, Jenny; Chung, Wendy K.; Colonna, Sarah V.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Daly, Mary B.; Dennis, Joe; Devilee, Peter; Dörk, Thilo; Dunning, Alison M.; Dwek, Miriam; Easton, Douglas F.; Eccles, Diana M.; Eriksson, Mikael; Evans, D. Gareth; Fasching, Peter A.; Fehm, Tanja N.; Figueroa, Jonine D.; Flyger, Henrik; Gabrielson, Marike; Gago-Dominguez, Manuela; García-Closas, Montserrat; García-Sáenz, José A.; Genkinger, Jeanine; Grassmann, Felix; Gündert, Melanie; Hahnen, Eric; Haiman, Christopher A.; Hamann, Ute; Harrington, Patricia A.; Hartikainen, Jaana M.; Hoppe, Reiner; Hopper, John L.; Houlston, Richard S.; Howell, Anthony; Jakubowska, Anna; Janni, Wolfgang; Jernström, Helena; John, Esther M.; Johnson, Nichola; Jones, Michael E.; Kristensen, Vessela N.; Kurian, Allison W.; Lambrechts, Diether; Le Marchand, Loic; Lindblom, Annika; Lubiński, Jan; Lux, Michael P.; Mannermaa, Arto; Mavroudis, Dimitrios; Mulligan, Anna Marie; Muranen, Taru A.; Nevanlinna, Heli; Nevelsteen, Ines; Neven, Patrick; Newman, William G.; Obi, Nadia; Offit, Kenneth; Olshan, Andrew F.; Park-Simon, Tjoung-Won; Patel, Alpa V.; Peterlongo, Paolo; Phillips, Kelly-Anne; Plaseska-Karanfilska, Dijana; Polley, Eric C.; Presneau, Nadege; Pylkäs, Katri; Rack, Brigitte; Radice, Paolo; Rashid, Muhammad U.; Rhenius, Valerie; Robson, Mark; Romero, Atocha; Saloustros, Emmanouil; Sawyer, Elinor J.; Schmutzler, Rita K.; Schuetze, Sabine; Scott, Christopher; Shah, Mitul; Smichkoska, Snezhana; Southey, Melissa C.; Tapper, William J.; Teras, Lauren R.; Tollenaar, Rob A. E. M.; Tomczyk, Katarzyna; Tomlinson, Ian; Troester, Melissa A.; Vachon, Celine M.; van Veen, Elke M.; Wang, Qin; Wendt, Camilla; Wildiers, Hans; Winqvist, Robert; Ziogas, Argyrios; Hall, Per; Pharoah, Paul D. P.; Adank, Muriel A.; Hollestelle, Antoinette; Schmidt, Marjanka K.; Hooning, Maartje J.; NBCS Collaborators; OSBREAC; ABCTB Investigators; kConFab Investigators.
I: Cancer Medicine, Bind 12, Nr. 15, 2023, s. 16142-16162.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
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 - Hoppe, Reiner
AU - Hopper, John L.
AU - Houlston, Richard S.
AU - Howell, Anthony
AU - Jakubowska, Anna
AU - Janni, Wolfgang
AU - Jernström, Helena
AU - John, Esther M.
AU - Johnson, Nichola
AU - Jones, Michael E.
AU - Kristensen, Vessela N.
AU - Kurian, Allison W.
AU - Lambrechts, Diether
AU - Le Marchand, Loic
AU - Lindblom, Annika
AU - Lubiński, Jan
AU - Lux, Michael P.
AU - Mannermaa, Arto
AU - Mavroudis, Dimitrios
AU - Mulligan, Anna Marie
AU - Muranen, Taru A.
AU - Nevanlinna, Heli
AU - Nevelsteen, Ines
AU - Neven, Patrick
AU - Newman, William G.
AU - Obi, Nadia
AU - Offit, Kenneth
AU - Olshan, Andrew F.
AU - Park-Simon, Tjoung-Won
AU - Patel, Alpa V.
AU - Peterlongo, Paolo
AU - Phillips, Kelly-Anne
AU - Plaseska-Karanfilska, Dijana
AU - Polley, Eric C.
AU - Presneau, Nadege
AU - Pylkäs, Katri
AU - Rack, Brigitte
AU - Radice, Paolo
AU - Rashid, Muhammad U.
AU - Rhenius, Valerie
AU - Robson, Mark
AU - Romero, Atocha
AU - Saloustros, Emmanouil
AU - Sawyer, Elinor J.
AU - Schmutzler, Rita K.
AU - Schuetze, Sabine
AU - Scott, Christopher
AU - Shah, Mitul
AU - Smichkoska, Snezhana
AU - Southey, Melissa C.
AU - Tapper, William J.
AU - Teras, Lauren R.
AU - Tollenaar, Rob A. E. M.
AU - Tomczyk, Katarzyna
AU - Tomlinson, Ian
AU - Troester, Melissa A.
AU - Vachon, Celine M.
AU - van Veen, Elke M.
AU - Wang, Qin
AU - Wendt, Camilla
AU - Wildiers, Hans
AU - Winqvist, Robert
AU - Ziogas, Argyrios
AU - Hall, Per
AU - Pharoah, Paul D. P.
AU - Adank, Muriel A.
AU - Hollestelle, Antoinette
AU - Schmidt, Marjanka K.
AU - Hooning, Maartje J.
AU - NBCS Collaborators
AU - OSBREAC
AU - ABCTB Investigators
AU - kConFab Investigators
N1 - Publisher Copyright: © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
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 - CHEK2 c.1100delC germline genetic variant
KW - contralateral breast cancer risk
KW - radiotherapy
KW - survival
KW - systemic treatment
U2 - 10.1002/cam4.6272
DO - 10.1002/cam4.6272
M3 - Journal article
C2 - 37401034
AN - SCOPUS:85182821176
VL - 12
SP - 16142
EP - 16162
JO - Cancer Medicine
JF - Cancer Medicine
SN - 2045-7634
IS - 15
ER -