http://repub.eur.nl/res/aut/6104/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/8130/ 2006-11-15T00:00:00Z Women with a strong family history of breast and/or ovarian cancer combined with young ages at diagnosis of affected family members have an increased risk of these types of cancer. In 1994 and 1995 respectively, the BRCA1 and BRCA2 genes were identified. A germline mutation in one of these genes is associated with very high risks of early onset breast and ovarian cancer. Current options for BRCA1/2 mutation carriers to reduce their risk of breast cancer or death by breast cancer include prophylactic mastectomy, prophylactic salpingo-oophorectomy, chemoprevention and screening. Screening for breast cancer is also offered to women with a familial predisposition, but without a proven BRCA1/2 mutation. Several studies have investigated the efficacy of mammographic screening, sometimes in combination with clinical breast examination (CBE)) in high-risk groups of women. However, the efficacy of mammography screening has never been clearly demonstrated. Sensitivity of mammography was low this group of women in comparison with post-menopausal women screened in population based studies, most likely because of the young screening age of and consequently frequent a high density of the breast tissue. MRI appeared to be a sensitive method for detection of breast cancer in a diagnostic setting. For this reason, in the late nineties several breast cancer screening studies comparing the value of MRI and mammography were set up in women with a genetic susceptibility. Results of pilot and preliminary studies showed in all of them a very high sensitivity of MRI, while sensitivity of mammography was never higher than 50%. Recently, the first results of four large prospective studies were published, among which the Dutch national MRISC study. In this thesis, the short-term results of the MRISC study are described. Two of the main objectives of the MRISC study are addressed in this thesis: 1. Assessment of the efficacy of screening in diagnosing early-stage breast cancer in women with a familial or genetic predisposition. 2. Assessment of the value of MRI in this screening scheme compared to mammography. http://repub.eur.nl/res/pub/8450/ 2004-01-01T00:00:00Z BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.