| A positive family history is the most important breast cancer risk factor. About 20% of breast cancer patients have one or more close relatives with the disease. It is estimated that 25% of all familial breast cancer can be explained by germline mutations with a dominant hereditary pattern, such as BRCA1, BRCA2, and p53, an additional 5% by a CHEK2 mutation, and in the remaining 70% other, as yet unknown, gene mutations play a role. The age of onset of the disease is younger than average and frequently occurs under the age of 50. One of the options for young women from these families to reduce their risk of (death of) breast cancer is intensive surveillance (screening) by means of radiologic imaging and clinical palpation. While randomized studies repeatedly have shown that population screening programmes in women aged 40-70 can significantly reduce breast cancer mortality, it is not known whether this is possible in younger women with an increased breast cancer risk due to a positive family history, and what would be the most optimal screening modality. To investigate these questions and especially the potential of MRI as a screening modality, the MRISC study, a Dutch multicenter study, started in 1999. To date, more than 1900 genetically susceptible women with a cumulative lifetime breast cancer risk of A positive family history of breast cancer is the most important risk factor for the disease. While about twenty percent of all breast cancer patients have at least one close relative with the disease, it is estimated that only 25% of these familial breast cancer cases can be explained by germline mutations with a dominant hereditary pattern, such as BRCA1, BRCA2, and p53 (1-3). An additional 5% is caused by a CHEK-2 mutation (4), and in the remaining 70% other, as yet unknown, gene mutations play a role. Hereditary breast cancer is characterized by a young age at onset, frequently before the age of 50. The main research question is to determine the mid-term (5-8 years) positive and negative effects of the MRISC-breast cancer screening programme. This question will be answered by the following separate side studies: In the Netherlands, a large number of women have a positive family history of breast cancer. A recent Dutch study estimated that, according to current national guidelines, 25% of the first-degree relatives of a breast cancer patient should be referred for regular surveillance in a family cancer clinic (23). It is therefore of the utmost importance to investigate the (cost-)effectiveness of this surveillance and precisely define the risk group(s) that should be included in such a screening programme. In addition, the most optimal and cost-effective screening scheme should be defined. The first results of the already mentioned MRISC study indicate that the combination of MRI, mammography and clinical palpation is highly sensitive and leads to the detection of breast tumours in an early, favourable stage. However, it is not known whether this protocol is cost-effective for all risk and age groups included. The data for the answering of the abovementioned research questions will be (further) collected by means of the registration forms that were already developed and used in the MRISC study. Data from the registration forms will be regularly entered into the database that was especially developed for this study. Ultimately (as of october, 1st, 2003), in the MRISC study 1909 women were included, among which 358 carriers of a BRCA1 or BRCA2 germline mutation. The numbers of included women from the six participating centers are as follows: 557 women from the NKI-AVL (Amsterdam), 510 by the Erasmus MC -Daniel den Hoed Cancer Center (Rotterdam), and 313, 241, 148 and 140 women from the Academic Hospitals of Leiden, Nijmegen, Amsterdam (VU) and Groningen, respectively. |
