Patient and tumor characteristics.

<p>Patient and tumor characteristics.</p

General classification and within-subtype classification of BRCA1 and BRCA2 breast cancers.

<p>Classification performances were assessed by leave-one-out cross-validation. TP, true positive; TN, true negative.</p>a<p>Mean balanced accuracy.</p>b<p>Fisher's exact test.</p

Cross-platform validation of the gene signatures.

<p>Validation of the basal <i>BRCA1</i> signature and lumB <i>BRCA2</i> signature were performed using samples analyzed by in-house spotted microarrays. Classification performances were assessed by leave-one-out cross-validation. TP, true positive; TN, true negative.</p>a<p>Mean balanced accuracy.</p>b<p>Fisher's exact test.</p

Validation of gene signatures in independent datasets.

<p>The basal BRCA1 signature and lumB BRCA2 signature was validated in two public available datasets. Classification performances were assessed by leave-one-out cross-validation. TP, true positive; TN, true negative.</p>a<p>Mean balanced accuracy.</p>b<p>Fisher's exact test.</p

Within-subtype classification of basal <i>BRCA1</i> and lumB <i>BRCA2</i> breast cancers.

<p>Expression data matrix of the 110-gene basal <i>BRCA1</i> signature (A) and the 100-gene lumB <i>BRCA2</i> signature (B) are visualized as heat maps. Rows correspond to genes and columns to samples. Tumors are ordered according to their <i>BRCA1/2</i> probability estimate obtained by leave-one-out cross-validation (lower panels). The germline mutation is shown as red (<i>BRCA1</i>), blue (<i>BRCA2</i>) or grey (sporadic). Dashed lines indicate the <i>BRCA1/2</i> probability cutoff. Samples with probabilities ≥0.5 are classified as <i>BRCA1/2</i>, while samples with probabilities <0.5 are classified as sporadic tumors.</p

Association between hereditary breast cancers and molecular subtypes.

<p>Distribution of molecular subtypes among <i>BRCA1</i>, <i>BRCA2</i> and sporadic breast cancer samples. Tumors were classified into molecular subtypes using the PAM50 classifier. Numbers in brackets refer to number of samples in each group.</p

Hierarchical clustering.

<p>Hierarchical clustering of 183 breast tumor samples using the 500 most variant genes across all samples. In the heat map rows correspond to genes and columns to samples. Red indicates elevated expression, green reduced expression.</p

Validation of the basal <i>BRCA1</i> signature and lumB <i>BRCA2</i> signature in independent datasets.

<p>A) The basal <i>BRCA1</i> signature was validated using basal-like tumor samples obtained from the NKI dataset and Jönsson dataset, respectively. The panels show the <i>BRCA1</i> probability estimates of basal-like <i>BRCA1</i> samples (red) and basal-like sporadic samples (grey). B) The lumB <i>BRCA2</i> signature was validated using lumB tumor samples obtained from the Jönsson dataset. The panel shows the <i>BRCA2</i> probability estimates of lumB <i>BRCA2</i> samples (blue) and lumB sporadic samples (grey). Probability estimates were obtained by leave-one-out cross-validation. Dashed lines indicate the <i>BRCA1/2</i> probability cutoff. Samples with probabilities ≥0.5 are classified as <i>BRCA1/2</i>, while samples with probabilities <0.5 are classified as sporadic tumors. Samples have been “jittered” in the vertical direction to spread them out for better visualization.</p

Associations between SNPs in the region surrounding rs9348512 on chromosome 6 and breast cancer risk.

<p>Results based on imputed and observed genotypes. The blue spikes indicate the recombination rate at each position. Genotyped SNPs are represented by diamonds and imputed SNPs are represented by squares. Color saturation indicates the degree of correlation with the SNP rs9348512.</p

Per allele hazard ratios (HR) and 95% confidence intervals (CI) of previously published breast cancer loci among <i>BRCA2</i> mutation carriers from previous reports and from the iCOGS array, ordered by statistical significance of the region.

1<p>Reporting status of the SNP is either previously reported or novel to this report.</p>2<p>p-value was calculated based on the 1-degree of freedom score test statistic.</p>3<p>rs311499 could not be designed onto the iCOGS array. A surrogate (r² = 1.0), rs311498, was included, however, and reported here.</p>4<p>Stronger associations were originally reported for the SNP, assuming a dominant or recessive model of the ‘risk allele’.</p