RESUMO
BACKGROUND: The addition of MRI to mammography and ultrasound for breast cancer screening has been shown to improve screening sensitivity for high risk women, but there is little data to date for women at average or intermediate risk. METHODS: Two thousand nine hundred and ninety-five women, aged 40 to 65 years with no previous history of breast cancer were enrolled in a screening program, which consisted of two rounds of MRI, ultrasound and mammography, one year apart. Three hundred and fifty-six women had a CHEK2 mutation, 370 women had a first-degree relative with breast cancer (and no CHEK2 mutation) and 2269 women had neither risk factor. Subjects were followed for breast cancer for three years from the second screening examination. RESULTS: Twenty-seven invasive epithelial cancers, one angiosarcoma and six cases of DCIS were identified over the four-year period. Of the 27 invasive cancers, 20 were screen-detected, 2 were interval cancers, and five cancers were identified in the second or third follow-up year (i.e., after the end of the screening period). For invasive cancer, the sensitivity of MRI was 86%, the sensitivity of ultrasound was 59% and the sensitivity of mammography was 50%. The number of biopsies incurred by MRI (n = 156) was greater than the number incurred by mammography (n = 35) or ultrasound (n = 57). Of the 19 invasive cancers detected by MRI, 17 (89%) were also detected by ultrasound or mammography. CONCLUSIONS: In terms of sensitivity, MRI is slightly better than the combination of mammography and ultrasound for screening of women at average or intermediate risk of breast cancer. However, because of additional costs incurred by MRI screening, and the small gain in sensitivity, MRI screening is probably not warranted outside of high-risk populations.
RESUMO
Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies. To establish the relative contributions of founder and nonfounder BRCA mutations, we established the entire spectrum of BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with origins in all regions of Poland. We sequenced the entire coding regions of the BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast cancer and in 100 families with cases of both breast and ovarian cancer. A mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in 63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119 (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2 families). In particular, 111 families (91.0%) carried one of the 3 common founder mutations. The mutation spectrum was not different between families with and without ovarian cancer. These findings suggest that a rapid and inexpensive assay directed at identifying the 3 common founder mutations will have a sensitivity of 86% compared to a much more costly and labor-intensive full-sequence analysis of both genes. This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention.