New Breast Cancer Study

A Study of Breast Cancer Pathology and Outcome in PALB2 Mutations Carriers

Background

Over the last 20 years, genetic testing for breast cancer susceptibility has been primarily focused on testing for mutations in the BRCA1 and BRCA2 genes. Through our increased understanding of breast cancer predisposition clinical genetic testing is expanding to incorporate other genes, including PALB2.  Inherited PALB2 mutations are rarer than BRCA1/BRCA2 and much less is known about the natural history and prognosis of women with PALB2-related breast cancer. Findings from a recent study suggest that PALB2-related breast cancer have a significantly worse prognosis than sporadic breast cancers, but this study was based on small numbers and considerable uncertainty remains.

Aims

a) To identify 200 women in the UK and internationally who have been diagnosed with breast cancer and who have a germline mutation in PALB2. To compare clinical details on presentation, histology, staging, family history, treatment, and outcome with matched women who have breast cancer but do not have germline PALB2 mutations. b) To further refine breast cancer risks for PALB2 mutation carriers and explore other cancer risks in families with PALB2 mutations.

Techniques and Methodology

Women with breast cancer and PALB2 mutations will be identified through two large breast cancer case-control studies SEARCH (Anglia region) and BRIDGES (Europe). In addition further cases will be identified by pioneering a new approach of prospective ascertainment though genetic centres in the UK. Comparisons will be made between women with breast cancer and PALB2 mutations versus affected women who do not have a PALB2 mutation. We will also analyse data from over 280 families with PALB2 mutations that have been collected by the PALB2 Interest group to refine estimate breast cancer risk estimates and risks of other cancers in PALB2 mutation carriers

Impact on breast cancer research

PALB2 is the third most important hereditary breast cancer gene after BRCA1 and BRCA2, but there are very limited published data on presentation, treatment response and outcome in women with inherited PALB2 mutations and breast cancer. This study is highly translational as it will directly provide important information for women with PALB2-related breast cancer. It will also provide further insight into breast carcinogenesis as the PALB2 protein interact directly with BRCA1 and BRCA2, and is a key component of the DNA double strand break repair network.