Gene expression refines triple-negative breast cancer diagnosis

Researchers at the Vall d’Hebron Institute of Oncology (VHIO) and University of North Carolina have conducted a study on gene expression in triple-negative breast cancer (so named because it lacks expression of oestrogen and progesterone receptors and does not overexpress HER2). The study, published in The Oncologist, concludes that triple-negative breast cancer is biologically diverse and therefore a molecular subtype classification could be used to guide therapies better and make research more targeted.

Breast tumours are currently classified as luminal if they test positive for hormone receptors, HER2-enriched if this receptor is overexpressed, or triple negative if they do not fall into either of these categories, which is the case of 15-20% of recently-diagnosed patients. Triple-negative tumours represent a major clinical challenge because they are an aggressive type of breast cancer usually found in younger women, and their treatment options are largely confined to chemotherapy, because of the absence of receptors amenable to targeted therapies.

The results of this study – after examining more than 7,000 genes – will have a major impact on clinical trials that focus on triple-negative breast cancer. For the first time ever, and as a result of characterising the molecules in triple-negative tumours, the researchers found that although hormone receptors and HER2 are not expressed in routine pathology techniques, gene expression reclassifies them as luminal or HER2-enriched. According to Dr Aleix Prat, “There is substantial discordance between the current classification and gene expression characterisation, and in fact one in three triple-negative tumours might not be triple negative at all.” So, triple-negative tumours with luminal or HER2-enriched molecular profiles might benefit from targeted therapies.

The clinical implications of the study, which analysed more than 1,700 samples, have been summarised by Dr Aleix Prat, head of the Translational Genomics Group at the Vall d’Hebron Institute of Oncology (VHIO) and an oncologist at the Breast Cancer Unit at the Vall d’Hebron University Hospital. “Triple-negative tumours are a diverse clinical entity and they cover all known molecular subtypes. Identifying them by means of genomic tests such as the PAM50 will refine their diagnosis and probably improve our therapeutic options. Genomic testing is not always available, and in these cases our study also highlights the need to identify hormone receptors and HER2 with the utmost care, considering the well-known reproducibility problems inherent to these pathological biomarkers in daily clinical practice.” The VHIO hopes that the PAM50 genomic test will become available this year.

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