AIM 4

Aim IV – Expression analysis in breast tumor tissue
The idea behind the project is that both the geno- and phenotype of the tumor as well as the patients own genotype, in combination with environmental factors, play a role both in breast cancer risk, the type of breast cancer they develop, the course of the disease, and the response to treatment. We will use the molecular profiles of breast tumors to stratify the patients for studying genetic predisposition (SNPs) and gene environment interaction. This design will allow us to stratify our analyses for low-penetrance gene identification and for gene environment interactions by the patient’s own tumor profile. Thus, otherwise low-penetrance breast cancer gene variants that are difficult to identify in classical case-control studies, may appear to be high-penetrance for certain subclasses, and therefore identifiable.

The tumor tissue biobank will consist of tissues from breast cancer patients participating in the post-genome cohort and as another buffered mRNA blood sample at the time of diagnosis. Since the NOWAC study is nationwide cases should be ascertained at all major hospitals in Norway. In order to have a simple rule for identification of potential participants in the NOWAC study we will use the single criteria of year of birth 1943-57. Within this age interval there are about 410 000 Norwegian women, where 140 000 of them will participate in the NOWAC within 2006 (35% of all Norwegian women).

In collaboration with the Norwegian Breast Cancer Group (NBCG), (see letter of collaboration) all woman diagnosed with a new breast cancer and born between 1943 and 1957 will be asked whether they previously have participated in the NOWAC study. If the answer is yes, they will be asked to give an informed consent for a pre-operative blood sample and for the permission to collect fresh tumor tissue for research purposes. A protocol for sampling a core biopsy at the time of diagnosis by the radiologist and cytologist has been prepared, and pilot studies including the main hospitals in Oslo and Tromsø under Southern and Northern Norway Regional Health Authority has already started (2003-2004