Tumor Gene Expression and Prognosis in Breast Cancer Patients with 10 or More Positive Lymph Nodes

Abstract

Purpose:This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)^positive, node-negative breast cancer patients. Experimental Design: Patients with z10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Results: Seventy-eight patients were studied. As of August 2002,77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical andimmunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantlyassociatedwithdistantrecurrence-freesurvival (DRFS).UnivariateCoxanalysisidentified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumorproteinp53-bindingprotein 2(TP53BP2) andtheERaxis genesPR and Bcl2.Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, includingTP53BP2 and Bcl2, as significant predictors of DRFS.

ASPP: a new family of oncogenes and tumour suppressor genes

“…A lowered ASPP2 expression was linked to a poor clinical outcome in diffuse large B-cell lymphoma (Lossos et al, 2002) and with poor distant recurrence-free survival in breast cancer patients (Cobleigh et al, 2005). Reduced expression of ASPP2 has also been observed in a microarray study of metastatic breast cancer samples compared to nonmetastatic samples (Sgroi et al, 1999), suggesting that ASPP2 might be associated with breast cancer progression.…”

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

“…Reduction in DOI:http://dx.doi.org/10.7314/APJCP.2012.13.5.1727 Vitamin D Signaling andApoptosis Specific Regulator of p53 in Breast Cancer ASPP2 expression has been observed in microarray study of both invasive and metastatic breast cancer samples compared to normal breast samples, suggesting possible involvement of ASPP2 in breast cancer progression (Sgroi et al, 1999). Study carried out by Cobleigh et al (2005) demonstrated independent association of ASPP2/ TP53BP2 gene with distal recurrence in breast cancer patients. They have linked higher ASPP2 expression with longer distal recurrence free survival.…”

8p deletion is strongly linked to poor prognosis in breast cancer

“…Several commercial molecular classifiers, based on multiplexed analyses of the RNAs of 21-70 gene products, have recently been introduced into the market in order to assist in therapy decisions making. [2][3][4] These purely RNA-based tests share the disadvantage that gradual changes of each parameter must be measured, and that these measurements are strongly dependent on tumor cell purity.…”