Volume 19, Issue 2, Pages 169-180 (February 2018) Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study  Ellen R Copson, PhD, Tom C Maishman, MSc, Will J Tapper, PhD, Ramsey I Cutress, PhD, Stephanie Greville-Heygate, MB, Prof Douglas G Altman, PhD, Bryony Eccles, MD, Sue Gerty, BSc, Lorraine T Durcan, BSc, Prof Louise Jones, PhD, Prof D Gareth Evans, MD, Prof Alastair M Thompson, MD, Prof Paul Pharoah, PhD, Prof Douglas F Easton, PhD, Alison M Dunning, PhD, Prof Andrew Hanby, BM, Prof Sunil Lakhani, MD, Prof Ros Eeles, PhD, Prof Fiona J Gilbert, MB, Hisham Hamed, MD, Prof Shirley Hodgson, DM, Peter Simmonds, MB, Louise Stanton, MSc, Prof Diana M Eccles, MD  The Lancet Oncology  Volume 19, Issue 2, Pages 169-180 (February 2018) DOI: 10.1016/S1470-2045(17)30891-4 Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 1 Trial profile BRCA-positive=patient with BRCA1 or BRCA2 pathogenic mutation. Patients were categorised as BRCA-negative if no BRCA pathogenic mutation was found or they had a BRCA1 or BRCA2 variant of uncertain significance or very low penetrance. The Lancet Oncology 2018 19, 169-180DOI: (10.1016/S1470-2045(17)30891-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 2 Overall survival for all patients (analysis population) by BRCA mutation status (A) Kaplan-Meier plot and (B) forest plot of corresponding univariable and multivariable hazard ratios. In (B), multivariable analysis was adjusted for age, body-mass index (BMI; kg/m2), grade, tumour size, HER2 status, oestrogen-receptor status, ethnicity, and use of taxane chemotherapy. Groups without a reference were assessed as a continuous variable. The dashed line separates the univariable analysis (UVA) from the multivariable analysis (MVA). Oestrogen-receptor-positive group assessed at 2, 5, and 10 years because the hazard ratio associated with oestrogen-positive status varies with time.16 HR=hazard ratio. *Number of events (number of patients) from complete data obtained before multiple imputation. The Lancet Oncology 2018 19, 169-180DOI: (10.1016/S1470-2045(17)30891-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions

Figure 3 Overall survival for all patients with triple-negative breast cancer* by BRCA mutation status (A) Kaplan-Meier plot and (B) forest plot of corresponding univariable and multivariable hazard ratios. In (B), multivariable analysis was adjusted for age, body-mass index (BMI; kg/m2), grade, tumour size, HER2 status, oestrogen-receptor status, ethnicity, and use of taxane chemotherapy. Groups without a reference were assessed as a continuous variable. The dashed line separates the univariable analyses (UVA) from the multivariable analyses (MVA). HR=hazard ratio. *Number of events (number of patients) from complete data obtained before multiple imputation. The Lancet Oncology 2018 19, 169-180DOI: (10.1016/S1470-2045(17)30891-4) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Terms and Conditions