The estimated proportion of hereditary breast and ovarian cancers among all breast and ovarian cancer cases is 5-10%. According to the literature, inherited mutations in the BRCA1 and BRCA2 tumour-suppressor genes, account for the majority of hereditary breast and ovarian cancer cases. The aim of this report is to present novel mutations that have not yet been described in the literature and pathogenic BRCA1 and BRCA2 mutations which have been detected in HBOC families for the first time in the last three years. In the period between January 2009 and December 2011, 559 individuals from 379 families affected with breast and/or ovarian cancer were screened for mutations in the BRCA1 and BRCA2 genes. and encode truncated proteins. Two of them are nonsense while one is a frameshift mutation. Also, 11 previously known pathogenic mutations were detected for the first time in the HBOC families studied here (three in BRCA1 and eight in BRCA2). All, except one cause premature formation of stop codons leading to truncation of the respective BRCA1 or BRCA2 proteins.
Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SNmetastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.
We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 x 10(-13), odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 x 10(-15), OR = 1.50).
An increase in the incidence of breast cancer in women aged (40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95 % CI = 1.019-1.045) and 1.014 (95 % CI = 1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC = 1.033 (95 % CI = 1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straight forward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden ofthe disease that is important in terms of public health and deserves further investigation of possible risk factors.
Background A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Methods Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristicsin sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. Results No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statisticallz significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Conclusion Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal womer using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicatorsof worse prognosis.