Research led by Aleix Prat, Principal Investigator of the Translational Genomics Group at the Vall d'Hebron Institute of Oncology (VHIO) in Barcelona, has shown that HER2 breast cancer can be classified as four different subtypes according to respective molecular characteristics.

A previous study by this same group had already proposed this sub-classification based on the ability to predict response to chemotherapy and anti-HER2 treatment.

This present study, recently published in the Journal of the National Cancer Institute (JNCI), consequently shows that the differences in survival and responses to chemotherapy and anti-HER2 treatment in HER2 breast cancer can, in part, be explained by the molecular differences identified within this disease.

It is therefore hoped that, in the near future, this more precise classification of HER2 breast cancer will facilitate even more targeted treatments tailored to patients.

Establishing the molecular subtype of any breast cancer is critical in selecting the optimal therapeutic strategy.

Up until recently, breast cancer was classified into three groups according to the presence or absence of hormone receptors and the HER2 receptor: hormone-sensitive, HER2 and triple negative (when not falling into either of the two former categories).

HER2 tumours account for between 15 – 20% of all breast cancers and are characterised by the presence of a high number of HER2 receptors and increased proliferative activity of their tumour cells.

This breast cancer type is notoriously aggressive, carrying with it a higher risk of disease relapse and death.

Over recent years however, current anti-HER2 therapies such as trastuzumab, lapatinib, and pertuzumab, have greatly improved outcomes for countless of patients suffering from this disease.

The catalyst behind the previous and present study led by Prat, both of which were funded in part through a Susan G. Komen Career Catalyst Research (CCR) Grant, was the discovery that not all HER2 tumors involve the same relapse risk – nor do they respond in the same way to chemotherapy, endocrine and anti-HER2 treatments.

This same observation had already led to research carried out by Aleix Prat, in collaboration with José Baselga, Physician-in-Chief of the Memorial Sloan Kettering Cancer Center (MSKCC), New York, USA, published in Clinical Cancer Research earlier this year, in which 156 HER2 tumour samples from the NOAH phase III clinical trial were analysed retrospectively.

They found that one of the molecular subtypes, the HER2-enriched subtype, showed a much better response to anti-HER2 therapy combined with chemotherapy than the other subtypes.

These findings have been confirmed by another group in a phase III study with 270 patients, CALGB40601, the results of which were presented earlier this year at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 30 – June 03, Chicago IL, USA.

Thanks to advances within the field, the genomic classification of breast cancer has been greatly refined revealing that there are at least four major subtypes (Luminal A, Luminal B, HER2-enriched and Basal-Like).

Last year, Prat's group finely tuned the classification of hormone-sensitive tumours by genomics.

“Now, again thanks to gene expression data, we have demonstrated that HER2 disease differs from the HER2-enriched molecular group and that the 4 subtypes of breast cancer are also represented within HER2 disease. This novel biological classification of HER2 disease is important and already showing potential clinical utility”, explains Prat.

Establishing genomic differences between subtypes and matching these with the clinical course of each will ultimately enable VHIO to deliver on the true promise of precision medicine.

In so doing, more aggressive treatments for those who stand to benefit from them will be identified; more targeted and less toxic therapeutic options will be sought – collectively resulting in extended survival and better quality of life for patients.

Prat cautions, “Although I have no doubt that in the near future we will be using the molecular subtypes to make personalised therapeutic decisions in HER2 breast cancer, for the moment, standard and current clinical practice should not be altered based on the identification of the subtype”.

He concludes, “Tests based on gene expression in breast cancer provide us with essential information for determining the benefits of treatment and both the short-term and long-term risk of relapse. This means that molecular characterisation of the tumour prior to deciding on the therapeutic approach is going to become increasingly more important. I believe we have to do everything in our power to ensure that this type of genomic testing can be implemented widely throughout the community. We have no other option but to follow this direction”.

Identification of the molecular subtypes in this study was performed using a genomic test known as PAM50 which, in contrast to other available tests, enables the biological characterisation of breast cancer and provides powerful prognostic information in postmenopausal women with hormone-sensitive breast cancer.

CatSalut’s Genomics Platform program has recently incorporated this test for use in hormone-sensitive breast cancer in a number of hospitals throughout Catalonia.

Source: Vall d'Hebron Institute of Oncology