BACKGROUND AND PURPOSE: Women carrying mutations in the CHEK2 gene are at an increased breast cancer risk. Data about outcome and prognosis for these patients after standard multimodality treatment are scarce at present. MATERIALS AND METHODS: One-hundred and fifty (150) patients with non-metastasized early-stage breast cancer (T1-2) receiving postoperative radiotherapy following breast-conservative surgery at our department were included in this analysis. Carriers were identified using mutation-specific restriction enzyme-based screening assays in previous investigations. Twenty-five breast cancer patients were heterozygous for one of three CHEK2 gene mutations (I157T, n=13; 1100delC, n=10; IVS2+1G>A, n=2). The comparison group consisted of 125 early-stage breast cancer patients without a CHEK2 gene mutation (non-carriers). Median follow-up was 87 months for the total cohort of patients. RESULTS: Local recurrences occurred in 13 patients (carriers, 3 (12%); non-carriers, 10 (8%)) and distant metastases occurred in 27 patients (carriers, 8 (32%); non-carriers, 19 (15%)). Twenty-five patients had deceased (carriers, 8 (32%); non-carriers, 17 (14%)) with all but 3 deaths related to breast cancer. Actuarial 7-year local relapse-free survival was 86% in carriers versus 90% in non-carriers (p=0.48). Actuarial metastasis-free, disease-free and overall survival at 7 years were 64% vs. 84% (p=0.045), 59% vs. 78% (p=0.07) and 69% vs. 87% (p=0.10), respectively. In a multivariate step-wise Cox regression analysis presence of a CHEK2 mutation remained a borderline significant discriminator for metastasis-free survival (p=0.048; OR=0.4; 95% CI 0.2-1.0) next to T-stage (p=0.001; OR 0.3; 95% CI 0.1-0.6). CONCLUSIONS: Heterozygosity for a germline CHEK2 mutation appears to represent an adverse prognostic factor in patients with early-stage breast cancer. If confirmed in larger studies these data may serve as a basis for future surveillance and treatment strategies taking into account individual germline mutational status.
BACKGROUND AND PURPOSE:Women carrying mutations in the CHEK2 gene are at an increased breast cancer risk. Data about outcome and prognosis for these patients after standard multimodality treatment are scarce at present. MATERIALS AND METHODS: One-hundred and fifty (150) patients with non-metastasized early-stage breast cancer (T1-2) receiving postoperative radiotherapy following breast-conservative surgery at our department were included in this analysis. Carriers were identified using mutation-specific restriction enzyme-based screening assays in previous investigations. Twenty-five breast cancerpatients were heterozygous for one of three CHEK2 gene mutations (I157T, n=13; 1100delC, n=10; IVS2+1G>A, n=2). The comparison group consisted of 125 early-stage breast cancerpatients without a CHEK2 gene mutation (non-carriers). Median follow-up was 87 months for the total cohort of patients. RESULTS: Local recurrences occurred in 13 patients (carriers, 3 (12%); non-carriers, 10 (8%)) and distant metastases occurred in 27 patients (carriers, 8 (32%); non-carriers, 19 (15%)). Twenty-five patients had deceased (carriers, 8 (32%); non-carriers, 17 (14%)) with all but 3 deaths related to breast cancer. Actuarial 7-year local relapse-free survival was 86% in carriers versus 90% in non-carriers (p=0.48). Actuarial metastasis-free, disease-free and overall survival at 7 years were 64% vs. 84% (p=0.045), 59% vs. 78% (p=0.07) and 69% vs. 87% (p=0.10), respectively. In a multivariate step-wise Cox regression analysis presence of a CHEK2 mutation remained a borderline significant discriminator for metastasis-free survival (p=0.048; OR=0.4; 95% CI 0.2-1.0) next to T-stage (p=0.001; OR 0.3; 95% CI 0.1-0.6). CONCLUSIONS: Heterozygosity for a germline CHEK2 mutation appears to represent an adverse prognostic factor in patients with early-stage breast cancer. If confirmed in larger studies these data may serve as a basis for future surveillance and treatment strategies taking into account individual germline mutational status.
Authors: Melissa C Southey; James G Dowty; Moeen Riaz; Jason A Steen; Anne-Laure Renault; Katherine Tucker; Judy Kirk; Paul James; Ingrid Winship; Nicholas Pachter; Nicola Poplawski; Scott Grist; Daniel J Park; Bernard J Pope; Khalid Mahmood; Fleur Hammet; Maryam Mahmoodi; Helen Tsimiklis; Derrick Theys; Amanda Rewse; Amanda Willis; April Morrow; Catherine Speechly; Rebecca Harris; Robert Sebra; Eric Schadt; Paul Lacaze; John J McNeil; Graham G Giles; Roger L Milne; John L Hopper; Tú Nguyen-Dumont Journal: NPJ Breast Cancer Date: 2021-12-09
Authors: Marjanka K Schmidt; Frans Hogervorst; Richard van Hien; Sten Cornelissen; Annegien Broeks; Muriel A Adank; Hanne Meijers; Quinten Waisfisz; Antoinette Hollestelle; Mieke Schutte; Ans van den Ouweland; Maartje Hooning; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Antonis C Antoniou; Volker Arndt; Marina Bermisheva; Natalia V Bogdanova; Manjeet K Bolla; Hiltrud Brauch; Hermann Brenner; Thomas Brüning; Barbara Burwinkel; Jenny Chang-Claude; Georgia Chenevix-Trench; Fergus J Couch; Angela Cox; Simon S Cross; Kamila Czene; Alison M Dunning; Peter A Fasching; Jonine Figueroa; Olivia Fletcher; Henrik Flyger; Eva Galle; Montserrat García-Closas; Graham G Giles; Lothar Haeberle; Per Hall; Peter Hillemanns; John L Hopper; Anna Jakubowska; Esther M John; Michael Jones; Elza Khusnutdinova; Julia A Knight; Veli-Matti Kosma; Vessela Kristensen; Andrew Lee; Annika Lindblom; Jan Lubinski; Arto Mannermaa; Sara Margolin; Alfons Meindl; Roger L Milne; Taru A Muranen; Polly A Newcomb; Kenneth Offit; Tjoung-Won Park-Simon; Julian Peto; Paul D P Pharoah; Mark Robson; Anja Rudolph; Elinor J Sawyer; Rita K Schmutzler; Caroline Seynaeve; Julie Soens; Melissa C Southey; Amanda B Spurdle; Harald Surowy; Anthony Swerdlow; Rob A E M Tollenaar; Ian Tomlinson; Amy Trentham-Dietz; Celine Vachon; Qin Wang; Alice S Whittemore; Argyrios Ziogas; Lizet van der Kolk; Heli Nevanlinna; Thilo Dörk; Stig Bojesen; Douglas F Easton Journal: J Clin Oncol Date: 2016-06-06 Impact factor: 44.544
Authors: Maren Weischer; Børge G Nordestgaard; Paul Pharoah; Manjeet K Bolla; Heli Nevanlinna; Laura J Van't Veer; Montserrat Garcia-Closas; John L Hopper; Per Hall; Irene L Andrulis; Peter Devilee; Peter A Fasching; Hoda Anton-Culver; Diether Lambrechts; Maartje Hooning; Angela Cox; Graham G Giles; Barbara Burwinkel; Annika Lindblom; Fergus J Couch; Arto Mannermaa; Grethe Grenaker Alnæs; Esther M John; Thilo Dörk; Henrik Flyger; Alison M Dunning; Qin Wang; Taru A Muranen; Richard van Hien; Jonine Figueroa; Melissa C Southey; Kamila Czene; Julia A Knight; Rob A E M Tollenaar; Matthias W Beckmann; Argyrios Ziogas; Marie-Rose Christiaens; Johanna Margriet Collée; Malcolm W R Reed; Gianluca Severi; Frederik Marme; Sara Margolin; Janet E Olson; Veli-Matti Kosma; Vessela N Kristensen; Alexander Miron; Natalia Bogdanova; Mitul Shah; Carl Blomqvist; Annegien Broeks; Mark Sherman; Kelly-Anne Phillips; Jingmei Li; Jianjun Liu; Gord Glendon; Caroline Seynaeve; Arif B Ekici; Karin Leunen; Mieke Kriege; Simon S Cross; Laura Baglietto; Christof Sohn; Xianshu Wang; Vesa Kataja; Anne-Lise Børresen-Dale; Andreas Meyer; Douglas F Easton; Marjanka K Schmidt; Stig E Bojesen Journal: J Clin Oncol Date: 2012-10-29 Impact factor: 44.544