Gene variant linked to breast cancer metastasis discovered

The identification of a common gene variant found in 70 percent of white women suggests breast cancer metastasis may be a hereditary disorder.

Metastasis, the process by which tumour cells move to other parts of the body, is responsible for around 90 percent of cancer deaths. Research from Rockefeller University in New York has identified a common, inherited variant in the PCSK9 gene that may play a role in breast cancer metastasis. Their study, published in Cell, discovered that mice genetically engineered with the human gene variant had a higher risk of metastasis.

'Metastasis we believe is, at least in part, a hereditary disorder,' said Professor Sohail Tavazoie, from Rockefeller University and co-author of the study. 'We have been so focused on the cancer cells, the "seeds", that we've ignored the germline – "the soil". It's now clear that focusing on the soil is critical.'

Previously, gene variants identified as playing a role in breast cancer metastasis have arisen in tumour cells, meaning they are not present in all other cells of the body (BioNews 1243, 1127, 948). As the PCSK9 variant is inherited, this study provides the first evidence that gene variants present in all of a patient's cells may be the important drivers of metastasis.

A large cohort study on Scandinavian breast cancer patients, conducted by Lund University in Sweden, further confirmed the results. They found that patients with this gene variant had a 22 percent risk of breast cancer metastasis within 15 years, compared to just two percent in those without it.

'Our results emphasise the importance of international collaboration, which by definition involves researchers and patient cohorts from multiple countries,' said Wenbin Mei, a graduate fellow from Rockefeller University and lead author of the study. 'Further, this demonstrates just how powerful human genetics has become. With new technologies that combine computational analysis with experimental models, we're in a great era to answer difficult questions.'

While this PCSK9 variant is common, Professor Tavazoie said patients should not be concerned. 'The majority of patients with early-stage breast cancers harbouring either variant will still never develop metastasis,' he explained. He is also optimistic that the risk of developing metastatic disease can be reduced in patients with this variant.

The PCSK9 variant is thought to be implicated in cardiovascular disease and is already targeted by pre-existing treatments. An antibody specific to the PCSK9 gene variant is used to block its activity in patients with high cholesterol. The researchers confirm that, in preclinical trials, this antibody is effective at suppressing metastasis and hope that patients at high-risk will be able to undergo clinical trials with this treatment in the future.