Project description:We analysed a cohort of breast papillary lesions cases with (n=4) or without (n=7) co-existed cancer for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan® MIP arrays. Cases included pure papilloma (withoout cancer) (n=7), papilloma cases synchronous with cancer (n=4). We have analysed copy number calling from these samples including carcinoma components of synchronous cases in order to understand the precursor relationship as well any biomarker for progression from papillary lesions to carcinoma.
Project description:• Atypical hyperplasias (AH) provide insights into early changes that may predispose breast epithelial cells to oncogenic transformation. • Of genes associated with premalignancy in prior studies, only mRNA levels of ESR1 and SFRP1 were detected in the present study. • Transcriptional profiling defined signatures distinguishing atypical hyperplasias. The patterns of expression were similar among hyperplastic lesions of lobular and ductal phenotype suggesting a common set of alterations underlying both lesions. Pathway analyses identified elevated expression of estrogen receptor alpha, androgen receptor and EGFR receptors and Rho signaling as central events nodes in the pathways altered in AH. • A set of 43 genes were identified as common targets using 2 different algorithms to detect signatures associated with AH. Knockdown of SFRP1 in a TERT immortalized breast epithelial cell line resulted in 14 genes from this signature being either up-regulated or down-regulated as observed in the expression profiles from AH. • The results demonstrate a signature of genes representing alterations that are common to the development of hyperplasias in both ductal and lobular epithelium. Loss of SFRP1 expression is a key player underlying the transcriptional changes in AH that directs a module of genes that can be used to improve reproducibility of diagnosis of AH.
Project description:Purpose: The biological subtypes of breast cancer designated as Luminal A, Luminal B, HER2+/ER-, and Basal-like are clinically important for prognosis and planning treatment strategies. Recognizing that there is a continuum in both the spectrum of breast cancer disease and the risk of survival, we sought to develop a clinical test for the biological subtypes using a supervised risk classier.Methods: Microarray and real-time quantitative RT-PCR (qRT-PCR) data from 189 samples, procured as fresh-frozen and formalin-fixed, paraffin-embedded tissues, were used to statistically select prototypical samples and genes for the biological subtypes of breast cancer. Predictions for biological subtype and risk of recurrence were determined for different stages of disease, treatments, and across analytical platforms. Results: The biological subtype predictions on a large combined microarray test set showed prognostic significance across all patients (1244 subjects; p<0.0001), on node negative patients with no adjuvant systemic therapy (738 subjects; p<0.0001), and on patients treated with endocrine therapy (404 subjects; p=0.001). Analysis of a neoadjuvant chemotherapy study revealed a high pathologic complete response (pCR) rate in HER2+/ER- and Basal-like patients. The subtype and risk predications were also highly significant when using the qRT-PCR assay from archived FFPE breast cancers. Conclusion: Our risk predictor based on distance to biological subtype centroids provides a continuous risk score that applies to all stages of breast cancer given current therapies. The assay can be performed using archived breast tissues and a real-time qRT-PCR assay, thus facilitating application to retrospective cohorts and clinical samples. Keywords: reference x sample Comparison of reference samples against treatment
Project description:Purpose: The biological subtypes of breast cancer designated as Luminal A, Luminal B, HER2+/ER-, and Basal-like are clinically important for prognosis and planning treatment strategies. Recognizing that there is a continuum in both the spectrum of breast cancer disease and the risk of survival, we sought to develop a clinical test for the biological subtypes using a supervised risk classier.Methods: Microarray and real-time quantitative RT-PCR (qRT-PCR) data from 189 samples, procured as fresh-frozen and formalin-fixed, paraffin-embedded tissues, were used to statistically select prototypical samples and genes for the biological subtypes of breast cancer. Predictions for biological subtype and risk of recurrence were determined for different stages of disease, treatments, and across analytical platforms. Results: The biological subtype predictions on a large combined microarray test set showed prognostic significance across all patients (1244 subjects; p<0.0001), on node negative patients with no adjuvant systemic therapy (738 subjects; p<0.0001), and on patients treated with endocrine therapy (404 subjects; p=0.001). Analysis of a neoadjuvant chemotherapy study revealed a high pathologic complete response (pCR) rate in HER2+/ER- and Basal-like patients. The subtype and risk predications were also highly significant when using the qRT-PCR assay from archived FFPE breast cancers. Conclusion: Our risk predictor based on distance to biological subtype centroids provides a continuous risk score that applies to all stages of breast cancer given current therapies. The assay can be performed using archived breast tissues and a real-time qRT-PCR assay, thus facilitating application to retrospective cohorts and clinical samples. Keywords: reference x sample
Project description:Long-term tamoxifen treatment significantly improves the survival of hormone receptor-positive (HR+) breast cancer (BC) patients. However, tamoxifen resistance remains a big challenge for endocrine therapy. We aimed to identify prognostic biomarkers for tamoxifen treatment and explore their role in tamoxifen resistance. We used Exiqon miRCURY™ LNA Array (v.18.0) to detect the miRNA expression profiles in the primary tumors and their matched recurrent/metastatic lesions from six HR+ breast cancer patients who relapsed after TAM treatment. Fold changes ≥ 2 and P values < 0.05 were defined as differential expression. We found that 28 miRNAs were significantly downregulated in recurrent/metastatic lesions compared to primary tumors, and 54 miRNAs were significantly upregulated.
Project description:Collection of human breast cancer gene expressed measured by GPL2567. This subpopulation of breast cancer has gene expression and clinical data which were used for survival prediction analysis; resulting in emphasizing the ABI1-based 7-gene prognostic signature, as a prospective multi-gene expression clinical biomarker of breast cancer aggressiveness and metastasis, and therapeutic target.