Differences in outcome of young breast cancer patients according to BRCA1 mutation status.

Abstract

Abstract Abstract #1044 Introduction
 5 to 10 % of all breast cancer and 25 % of early onset breast cancer are inheritable, which may be caused by mutations of tumour suppressor genes such as BRCA1. Moreover, the issue of a familial breast cancer has raised much attention in recent years due to numerous medical and social implications. In the present paper we investigate the clinical characteristic and outcomes of younger (<50 years old) breast cancer patients with BRCA1 mutation in comparison to patients without this germline mutation.
 Methods and Materials
 This is an ongoing study and patients will be enrolled till end of 2008. Till now we followed 495 breast cancer patients who were diagnosed before age 50 and were asked to provide a blood sample for BRCA1 mutation screening. We compared contralateral breast cancer and ovarian cancer incidence, disease free, metastases free, and overall survival, between BRCA1 mutation carriers and non-carriers.
 Results
 BRCA1 mutations were detected in 90 breast cancer patients (5382insC in 60 patients, 300T/G in 18 pts, 185delAG in 10 pts, and 4153delAin 2 pts); the remaining 405 women did not carry the mutation. BRCA1 related tumours showed higher grade, higher Ki67 protein expression, more frequent negative oestrogen, progesterone, HER2-neu receptor status. Patients with BRCA1 mutation had a higher incidence of bilateral breast (40% compared to 10% in non mutated patients) and ovarian cancer (16% compared to less than 1% in non mutated patients. 10-years OS (overall survial) was 81% in no BRCA1 mutation patients compare to 88% in mutated BRCA1 patients (p=0.7), 10-years DSF (local-regional and distant failure) was 81% vs. 67% (p=0.8), 10-years MFS (metastases free survival) was 85% vs 71% (p=0.1), and 10-years RFS (recurrence free survival) was 90% vs. 80% (p=0.1) respectively.
 Multivariate Cox analysis for DFS showed that node ratio > 12% (HR=2.12), increasing tumour diameter (HR=1.23), experienced significantly decreased DFS. Furthermore, overall survival analysis also showed that node ratio > 12% (HR=2.65), increasing tumour diameter (HR=1.23), experienced significantly decreased OS. There is an insignificant trend for patients without BRCA1 mutation and younger to have worse DFS (HR=1.28) and worse OS (HR=2.23).
 Conclusions
 Patients with BRCA1 mutations have higher incidence of bilateral breast and ovarian cancer which imposes the need for frequent and careful follow-up after therapy. Node ratio and tumour diameter are the strongest prognostic factors. A final conclusion will require more patients and longer follow up. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1044.