Triple-negative breast cancer (TNBC) is defined by a lack of expression of estrogen, progesterone, and HER2 receptors, and genetically most of them fall into the basal subgroup of breast cancer. The important issue of TNBC is poorer clinical outcome and absence of effective targeted therapy. In this study, we sought to identify DNA copy number alterations and expression of relevant genes characteristic of TNBC to discover potential therapeutic targets. Frozen tissues from 114 breast cancers were analyzed using high-resolution array comparative genomic hybridization. The classification into subtype was determined by estrogen and progesterone receptor expression, and by the presence or absence of gain on the ERBB2 containing clone. The ACE algorithm was used for calling gain and loss of clones. Twenty-eight cases (25%) were classified as TNBC. Recurrent gains (> or =25%) unique to TNBC were 9p24-p21, 10p15-p13, 12p13, 13q31-q34, 18q12, 18q21-q23, and 21q22. Two published gene expression array data sets comparing basal subtype versus other subtype breast cancers were used for searching candidate genes. Of the genes upregulated in the basal subtype, 45 of 686 genes in one data set and 59 of 1,428 in the second data set were found to be located in the gained regions. Of these candidate genes, gain of NFIB (9p24.1) was specific for TNBC in a validation set by real-time PCR. In conclusion, we have identified recurrently gained regions characteristic of TNBC, and found that NFIB copy number and expression is increased in TNBC across the data sets. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

Background: A considerable proportion of estrogen receptor (ER)-positive breast cancer recurs despite tamoxifen treatment, which is a serious problem commonly encountered in clinical practice. We tried to find novel prognostic markers in this subtype of breast cancer.

We tried to establish models that predict systemic recurrence in breast cancer by selecting marker clones with DNA copy number alterations (CNAs) using an array comparative genomic hybridization (CGH). Array CGH containing 4,044 human bacterial artificial chromosome clones was used to assess CNAs in 62 primary breast cancer tissues from 31 patients with systemic recurrence within 5 years after surgery and clinicopathologically well matched 31 patients who had no evidence of disease for at least 5 years. Fourteen significant clones (11 clones showing gain and 3 showing loss) were identified by systemic recurrence-free survival (SRFS) analysis and 23 significant clones (17 clones showing gain and 6 showing loss) identified by v 2 test and FDR test were selected as predictive markers of systemic breast cancer recurrence. The significant CNAs were found in the chromosomal regions of 5p15. 33, 11q13.3, 15q26.3, 17q25.3, 18q23 and 21q22.3 with gain and 9p12, 11q24.1 and 14q32.33 with loss. We devised 2 prediction models for the systemic recurrence of breast cancer based on the 14 clones and the 23 clones, respectively. The survivals of the patients were significantly separated according to the scores from each model at the optimal cut off values in SRFS and overall survival analysis. We found candidate clones and genes of which CNAs were significantly associated with systemic recurrence of breast cancer. The devised prediction models with these clones were effective at differentiating the recurrence and nonrecurrence. ' 2008 Wiley-Liss, Inc.Key words: array CGH; copy number alteration; breast cancer; systemic recurrence; predictive marker Many breast cancer patients share clinicopathological characteristics, such as, age, pathologic features, stage and so forth. However, despite the similar treatments used, breast cancer recurs in some patients but not in others. The recurrence of breast cancer is generally classified into 3 categories, i.e., local, regional and systemic recurrence, and of these, systemic recurrence is most closely related with survival rate. Although clinicians do their best to treat recurred patients using chemotherapy, hormonal therapy, radiation therapy and surgical options, the results of these treatments are generally poor.Several prognostic models have devised based on clinicopathological factors, such as, the St. Gallen criteria, 1 the National Institutes of Health Consensus Guidelines, 2 the Nottingham Prognostic Indicator 3 and Adjuvant Online, 4 but these have many limitations in terms of predicting systemic recurrence. There is an urgency to identify patients that require radical treatment because they have a high risk of recurrence, and conversely to identify those with a low risk of recurrence, but it is difficult to precisely predict systemic recurrence. At the present time, little is known of the factors correlated with systemic recurrence in breast cancer, despite the enormous amount of research conducted.Recently, microarray technology has enabled investigators to do undertake who...