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Biomarkers may represent therapeutic targets for male breast cancer
Expression of two proteins in men with breast cancer appeared associated with poorer survival, according to study results.
If validated, these biomarkers — eIF4E and eIF5 — could serve as viable therapeutic targets, researchers wrote.
“Our work adds further evidence that the underlying biology of male and female breast cancer is fundamentally different from one another,” Matthew P. Humphries, MD, postdoctoral research fellow at University of Leeds School of Medicine in the United Kingdom, told HemOnc Today. “We have identified hundreds of genes which map to different biologically conserved molecular pathways within each gender. These differentially expressed genes may yet highlight additional targets for therapeutic intervention.”
Men account for approximately 1% of breast cancer cases. However, the disease is understudied due to the limited patient population, a lack of research funding and the fact that the majority of breast cancer clinical trials exclude men. Consequently, most treatment plans for men are informed by clinical studies that have been performed in women.
Humphries and colleagues performed a transcriptomic investigation of male and female breast cancer, confirming transcriptomic data in silico.
Investigators then immunohistochemically assessed biomarkers in 697 male breast cancers (training set, n = 477; validation set, n = 220). They also quantified biomarkers in pre- and posttreatment samples from a male with breast cancer who received everolimus (Afinitor, Novartis) — an mTOR inhibitor — and dactolisib (BEZ235, Novartis), a dual PI3K/mTOR inhibitor.
Humphries and colleagues used this data to identify sex-specific gene expression patterns pertaining to breast cancer.
They determined eIF protein transcripts were upregulated in male breast cancer. An analysis of the validation set revealed that eIF4E expression alone (HR = 1.77; P = .013), eIF5 expression alone (HR = 1.68; P = .035) and coexpression (HR = 2.66; P = .01) correlated with poorer OS.
Multivariate Cox regression analysis showed the associations persisted for eIF4E expression alone (HR = 2.38; P = .016), eIF5 expression alone (HR = 2.55; P = .022) and coexpression (HR = 7.04; P = .001).
“Men often feel ‘adrift in a sea of pink’ in the context of breast cancer research,” Humphries said. “It’s essential we continue to fund and investigate how male and female breast cancers differ to ensure each patient receives the most suitable treatment. The concept of truly personalized medicine cannot be achieved without specific and sensitive biomarkers that not only predict patient outcome but also inform treatment to give each person with breast cancer — regardless of gender — the best chance for survival.”
Researchers also observed “marked reduction” in eIF4E and eIF5 expression and extended survival after treatment with everolimus and dactolisib. This suggests mTOR inhibitors — many of which are already available — could be used to target this pathway.
“The repurposing of existing drugs allows the possibility of targeting these proteins, known to impact survival, which may improve treatment for at least a subset of male breast cancers patients,” Humphries said. – by Kyle Doherty
For more information:
Matthew P. Humphries, MD, can be reached at m.humphries@leeds.ac.uk.
Disclosure: The researchers report no relevant financial disclosures.