Molecular portraits of human breast tumours

Abstract

Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.

Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer

“…Moreover, NuclErbB-2 positivity was a significant independent predictor of poor survival in patients with MembErbB-2 overexpression. NuclErbB-2 also resulted a marker of lower overall survival in the subgroup of patients with tumors MembErbB-2+/ER-PR-, included in the ErbB-2-positive molecular subtype [23-25]. This latter finding for the first time highlights NuclErbB-2 presence as a molecular signature that might help to define two biologically distinct subsets of tumors within the ErbB-2-positive molecular subtype.…”

“…In addition, patients bearing tumors with both MembErbB-2 and NuclErbB-2 had worse OS compared with patients whose tumors showed only MembErbB-2 (Figure 2C). In the molecular classification of breast cancer, tumors which lack ER and PR and overexpress MembErbB-2 (MembErbB-2+/ER-PR-) (Table 7) have been included in the ErbB-2-positive molecular subtype, associated with poor outcome [23-25]. Here we observed a significantly lower OS in the subset of patients with MembErbB-2+/ER-PR-tumors expressing NuclErbB-2 as compared to those whose tumors lack NuclErbB-2 (Figure 2D).…”

“…Here we observed a significantly lower OS in the subset of patients with MembErbB-2+/ER-PR-tumors expressing NuclErbB-2 as compared to those whose tumors lack NuclErbB-2 (Figure 2D). Breast tumors expressing ER and PR and lacking MembErbB-2 (MembErbB-2-/ER+PR+), included in the luminal A molecular subtype [23-25], represent the subgroup with better prognosis of this study cohort. We found that the presence of NuclErbB-2 within this subgroup is significantly associated with larger tumor size, lymph node positivity, and higher clinical stages and grades (Table 7).…”

Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

“…initially proposed a molecular classification for breast cancer. Using a cDNA microarray of 38 breast cancer cases, this group defined a list of intrinsic genes 27, 28. Moreover, a larger cohort of breast cancer patients revealed that the luminal subgroup may be divided into luminal A and B 29.…”

Induction of a novel isoform of the lncRNA HOTAIR in Claudin‐low breast cancer cells attached to extracellular matrix

“…Human breast cancer is classified into ‘intrinsic subtypes’: luminal A, luminal B, basal, Claudin‐low, and HER2‐enriched based on gene expression profiles (Perou et al ., 2000; Prat and Perou, 2011; Sorlie et al ., 2001). This molecular stratification complements the pathological classifiers of breast cancer, namely estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and is preserved in the established human breast cancer cell lines (Holliday and Speirs, 2011; Parker et al ., 2009; Prat and Perou, 2011).…”