Building on the world’s largest breast cancer study, BC Cancer Agency scientists map the relationship between cancer mutations and clinical outcomes in 2,433 women.

Dr. Samuel Aparicio co-led a study with Dr. Carlos Caldas from Cancer Research UK and these teams have shown that what lies beneath the surface is critical as no two breast cancers are alike when you dig deeper. Building on a landmark study the team published in Nature called METABRIC, these findings provide compelling evidence that categorizing the biology of each woman’s breast cancer should become a precursor before a patient is enrolled in a clinical trial.  

“By observing the pattern of single nucleotide mutations in 2,433 breast cancers from the METABRIC study with associated patient outcomes, we can see that the prognosis associated with individual “driver” mutations depends on the molecular subgroup of breast cancer,” said Dr. Aparicio.

“This finding is of significance when considering which patients to enrol into clinical trials of agents directed at the drivers because the same mutation will already be associated with a different underlying prognosis, depending on the molecular subtype of the tumour.  This should be accounted for in the precision medicine approaches to trial design for experimental drugs targeting the drivers mutations in breast cancer.”

Even if two women presented with seemingly similar types of breast cancer with the same mutations, the underlying biology of each woman’s disease is highly diverse and this impacts their prognosis. If these two women were presented with the same treatment, one may respond well, while the other may not have a positive outcome.

One size does not fit all when it comes to cancer treatment. This research not only reinforces that long known fact, but also proves that overarching categories or subtypes of breast cancer are not enough when it comes to understanding the true nature of each patient’s disease and deciding what type of treatment they require.

By delving deeper into the biological make-up of more than 2,400 breast cancers, the team has also uncovered a host of mutations already linked to other cancer types that could immediately help to expand treatment options. A treatment that may work in targeting the biology of a renal or bladder cancer could be relevant for breast cancers with mutations in the same genes.

A key aim of precision cancer medicine is to tailor clinical management based on the specific events that are relevant to tumour development and progression. The breadth of this study provides a richer understanding of the genomic landscape of breast cancer, and offers new insights into the complexity of each tumour and how vital the full molecular picture is in developing the future clinical management of patients.

 

Dr. Aparicio says the next steps are to develop a practical and rapid way of typing breast cancers based on the molecular subtype so that women wishing to enrol in clinical trials can be directed to an appropriate study.

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