Molecular characteristics of recurrent triple-negative breast cancer

Abstract

Due to the fact that the treatment of breast cancer depends significantly on the molecular markers present in the cancer, including estrogen receptor (+), progesterone receptor (+) or erbB2 receptor (+), further investigation targeting triple-negative breast cancer (TNBC) subtypes may assist in elucidating the mechanisms of recurrence of TNBC and enable the identification of novel therapeutic strategies for patients with TNBC. The aim of the present study was to compare the gene expression profiles between TNBC samples that were identified as having recurrent and non-recurrent statuses. Between June 2011 and May 2012, a total of 30 patients with TNBC were examined using a follow-up period of at least 5 years. Their clinicopathological information was retrospectively reviewed and they were classified with a status either of recurrence [n=15 stage II (9), IIIA (2), IIIC (4)] or non-recurrence [n=15 stage II (6), IIIA (1), IIIC (8)]. The total RNA from tissue samples obtained from the recurrent and non-recurrent TNBC patients were used to performed oligonucleotide microarray analysis. The dataset was analyzed using GeneSpring software and validated using reverse transcription-quantitative polymerase chain reaction. Principal component analysis demonstrated that there was a marked difference in the gene expression distribution between the stage IIIc recurrent samples and early stage (stages IIa, IIb and IIIa) recurrent samples. In early stage recurrence, the significant pathway-associated upregulated genes were matrix metalloproteinases (MMPs) and genes associated with cancer cell migration (CDH2) and cell adhesion/motility (KRAS, CDC42, RAC1, ICAM and SRGAP2). By contrast, during stage IIIc recurrence, the significant pathway-associated upregulated genes in the recurrent samples were WNT signaling genes, including WNT 4 and WNT 16. It was concluded that there were markedly different distributions and gene expression profiles between stage IIIc recurrent TNBC tumors and early stage (IIa, IIb, IIIa) recurrent TNBC tumors, which provides important information for the development of effective treatment strategies for TNBC.

A comparison of the molecular subtypes of triple-negative breast cancer among non-Asian and Taiwanese women

“…Total RNA was extracted from these TNBC tissue samples, and the RNA samples were used to conduct oligonucleotide microarray analysis by the Genome Research Center, National Yang-Ming University [27]. …”

Multimodal Assessment of Estrogen Receptor mRNA Profiles to Quantify Estrogen Pathway Activity in Breast Tumors

“…48 The concept of using statistical summaries of the expression of gene sets, including PC analysis, to estimate the activity of specific molecular pathways has been widely used to study breast cancer, such as triple-negative breast cancer. 49 This type of analysis is also useful when attempting to integrate data from multiple…”

Novel immune cell subtypes linked to survival among African American women with triple-negative breast cancer

“…PHC1 (Polyhomeotic Homolog 1) encodes a component of a protein complex required to maintain the transcriptionally repressive state of many developmental transcripts, and was utlilized in an MCM2-targeted treatment strategy that successfully induced DNA damage and subsequent apoptosis in murine invasive breast cancer cells (43). Finally, SRGAP2 (SLIT-ROBO Rho GTPase Activating Protein 2) encodes a protein that regulates actin dynamics to regulate cell migration and differentiation and plays a role in cortical neuron development, and was found to be upregulated in early stage recurrent TNBC (44).…”