Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival-Reference-Cited by-同舟云学术

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

Published:2023-02-13 Issue: Volume: Page:
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Morra Anna¹,Schreurs Maartje A. C.²,Andrulis Irene L.³,Anton-Culver Hoda⁴,Augustinsson Annelie⁵,Beckmann Matthias W.⁶,Behrens Sabine⁷,Bojesen Stig E.⁸,Bolla Manjeet K.⁹,Brauch Hiltrud¹⁰,Broeks Annegien¹,Buys Saundra S.¹¹,Camp Nicola J.¹¹,Castelao Jose E.¹²,Cessna Melissa H.¹³,Chang-Claude Jenny⁷,Chung Wendy K.¹⁴,Collaborators NBCS,Colonna Sarah V.¹¹,Couch Fergus J.¹⁵,Cox Angela¹⁶,Cross Simon S.¹⁶,Czene Kamila¹⁷,Daly Mary B.¹⁸,Dennis Joe⁹,Devilee Peter¹⁹,Dörk Thilo²⁰,Dunning Alison M.⁹,Dwek Miriam²¹,Easton Douglas F.⁹,Eccles Diana M.²²,Eriksson Mikael¹⁷,Evans D. Gareth²³,Fasching Peter A.⁶,Fehm Tanja N.²⁴,Figueroa Jonine D.²⁵,Flyger Henrik⁸,Gabrielson Marike¹⁷,Gago-Dominguez Manuela²⁶,García-Closas Montserrat²⁷,García-Sáenz José A.²⁸,Genkinger Jeanine¹⁴,Grassmann Felix²⁹,Gündert Melanie⁷,Hahnen Eric³⁰,Haiman Christopher A.³¹,Hamann Ute⁷,Harrington Patricia A.⁹,Hartikainen Jaana M.³²,Hoppe Reiner¹⁰,Hopper John L.³³,Houlston Richard S.³⁴,Howell Anthony³⁵,Investigators ABCTB³⁶,Investigators kConFab³⁷,Jakubowska Anna³⁸,Janni Wolfgang³⁹,Jernström Helena⁵,John Esther M.⁴⁰,Johnson Nichola³⁴,Jones Michael E.³⁴,Kristensen Vessela N.⁴¹,Kurian Allison W.⁴²,Lambrechts Diether⁴³,Marchand Loic Le⁴⁴,Lindblom Annika¹⁷,Lubiński Jan³⁸,Lux Michael P.⁶,Mannermaa Arto³²,Mavroudis Dimitrios⁴⁵,Mulligan Anna Marie⁴⁶,Muranen Taru A.⁴⁷,Nevanlinna Heli⁴⁷,Nevelsteen Ines⁴⁸,Neven Patrick⁴⁸,Newman William G.²³,Obi Nadia⁴⁹,Offit Kenneth⁵⁰,Olshan Andrew F.⁵¹,Park-Simon Tjoung-Won²⁰,Patel Alpa V.⁵²,Peterlongo Paolo⁵³,Phillips Kelly-Anne⁵⁴,Plaseska-Karanfilska Dijana⁵⁵,Polley Eric C.¹⁵,Presneau Nadege²¹,Pylkäs Katri⁵⁶,Rack Brigitte³⁹,Radice Paolo⁵⁷,Rashid Muhammad U.⁷,Rhenius Valerie⁹,Robson Mark⁵⁰,Romero Atocha⁵⁸,Saloustros Emmanouil⁵⁹,Sawyer Elinor J.⁶⁰,Schmutzler Rita K.³⁰,Schuetze Sabine³⁹,Scott Christopher¹⁵,Shah Mitul⁹,Smichkoska Snezhana⁶¹,Southey Melissa C.⁶²,Tapper William J.²²,Teras Lauren R.⁵²,Tollenaar Rob A.E.M.¹⁹,Tomczyk Katarzyna³⁴,Tomlinson Ian²⁵,Troester Melissa A.⁵¹,Vachon Celine M.¹⁵,Veen Elke M. van²³,Wang Qin⁹,Wendt Camilla¹⁷,Wildiers Hans⁴⁸,Winqvist Robert⁵⁶,Ziogas Argyrios⁴,Hall Per¹⁷,Pharoah Paul D.P.⁹,Adank Muriel A.⁶³,Hollestelle Antoinette²,Schmidt Marjanka K.⁶³,Hooning Maartje J.²

Affiliation:

1. The Netherlands Cancer Institute

2. Erasmus MC Cancer Institute

3. Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital

4. University of California Irvine

5. Lund University

6. University Hospital Erlangen

7. German Cancer Research Center (DKFZ)

8. Copenhagen University Hospital

9. University of Cambridge

10. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology

11. University of Utah

12. Instituto de Investigación Sanitaria Galicia Sur (IISGS), Xerencia de Xestion Integrada de Vigo-SERGAS

13. Intermountain Healthcare

14. Columbia University

15. Mayo Clinic

16. University of Sheffield

17. Karolinska Institutet

18. Fox Chase Cancer Center

19. Leiden University Medical Center

20. Hannover Medical School

21. University of Westminster

22. University of Southampton

23. University of Manchester, Manchester Academic Health Science Centre

24. University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf

25. The University of Edinburgh

26. Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, SERGAS

27. National Cancer Institute, National Institutes of Health, Department of Health and Human Services

28. Instituto de Investigación Sanitaria San Carlos (IdISSC), Centro Investigación Biomédica en Red de Cáncer (CIBERONC)

29. Health and Medical University

30. Faculty of Medicine and University Hospital Cologne, University of Cologne

31. University of Southern California

32. University of Eastern Finland

33. The University of Melbourne

34. The Institute of Cancer Research

35. University of Manchester

36. University of Sydney

37. Peter MacCallum Cancer Center

38. Pomeranian Medical University

39. University Hospital Ulm

40. Stanford University School of Medicine

41. Oslo University Hospital and University of Oslo

42. Stanford Cancer Institute, Stanford University School of Medicine

43. KU Leuven

44. University of Hawaii Cancer Center

45. University Hospital of Heraklion

46. University of Toronto

47. University of Helsinki

48. Leuven Cancer Institute, University Hospitals Leuven

49. University Medical Center Hamburg-Eppendorf

50. Memorial Sloan Kettering Cancer Center

51. University of North Carolina at Chapel Hill

52. American Cancer Society

53. IFOM ETS - The AIRC Institute of Molecular Oncology

54. Peter MacCallum Cancer Centre

55. MASA

56. University of Oulu

57. Fondazione IRCCS Istituto Nazionale dei Tumori (INT)

58. Hospital Universitario Puerta de Hierro

59. University Hospital of Larissa

60. King's College London

61. Ss. Cyril and Methodius University in Skopje, Medical Faculty, University Clinic of Radiotherapy and Oncology

62. Monash University

63. The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital

Abstract

Abstract 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. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of 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)]. In 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. (Main MS: 3201 words)

Publisher

Research Square Platform LLC

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