P2-12-03: A Prospective Study of the Prognostic Implications of Being a BRCA1 Carrier for Young Onset Breast Cancer Patients.
Authors: Eccles DM , Dent L , Gerty SM , Altman D , Copson ER , Simmonds PD , Durcan L , Ward D 
Published: June 2012

Abstract
Background
BRCA1 gene carriers frequently develop triple negative breast cancer (TNBC) at young ages. Retrospective studies have reached conflicting conclusions about the prognostic implications of breast cancer diagnosed on a background of a constitutional BRCA1 gene mutation. Many studies have the disadvantages of retrospective design and small numbers or both. The Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) recruited 3024 patients diagnosed before 41 years of age and treated for breast cancer in the UK between 2000 and 2007 (protocol published: Eccles et al BMC Cancer 2008).
Aim: To investigate the effect of family history and BRCA1 gene mutation status on breast cancer survival in women aged younger than 41 years at diagnosis.
Methods: Cases in which the primary tumour pathology report was not available (2.8% of total) were excluded from this analysis. A completed family history questionnaire was available for 2907 cases (99% of total). The primary end point for this analysis was the development of distant metastases from breast cancer. All patients were younger than the starting age for screening in the UK except for known gene carriers of which there were only 8 in total, the remainder of identified gene carriers were tested after cancer diagnosis or as part of this study. Over 90% of patients received adjuvant or neoadjuvant chemotherapy with over 90% of these receiving an anthracycline based regimen. Kaplan Meier survival analysis and log rank test were used to assess survival differences.
Results: 2937 patients were included in the analysis. Mean and median age at diagnosis was 36 years and the cohort was followed prospectively for a mean and median follow up time of 50 months. Overall distant disease free survival in the whole cohort was only 75% at 5 years. The effect of family history on presentation was explored. Patients who reported a first or second degree relative with breast cancer presented with smaller tumours (20mm compared to 22.5mm, p= 0.006) but no difference in axillary nodal status (p=0.2605). Survival was however significantly better comparing the 499 patients who reported a family history of breast cancer compared with the rest of the cohort (p=0.0164). 539 patients had been tested for mutations in the BRCA1/2 genes and 176 high risk gene BRCA1/BRCA2 carriers were identified. We compared 118 patients with a known BRCA1 gene mutation (almost all diagnosed after the cancer) to the 465 patients with confirmed TNBC (p=0.0118). Survival was significantly better in the BRCA1 carriers (p=0.0118). After excluding 29 gene carriers whose primary tumour showed any of ER, HER2 or PR as positive, the same improved survival trend was seen although significant at the 10% level (p=0.07).
Conclusion: This prospective study indicates that BRCA1 gene carriers clearly do not have a worse prognosis when compared to triple negative breast cancers or young onset breast cancer overall and these early follow up data indicate an improved outlook in gene carriers.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-03.