B.C. research alters view of breast tumours

Not all cells in a breast cancer tumour contain the same mutations, researchers in British Columbia have found.

The finding that changes occur in tumours over time could change how scientists think about developing new breast cancer drugs and deciding which patients would benefit most from treatments.

In Wednesday's issue of the journal Nature, Samuel Aparicio and his colleagues at the BC Cancer Agency charted the genetic mutations that occurred in the 3billion letters of the DNA sequence from an estrogen-receptor-alpha-positive breast tumour.

"The impact is going to be in the waythat cancer researchers look at developing therapies and applying therapies in the short term," said Aparicio, chair of breast cancer research at theBC Cancer Agency and Canada research chair in molecular oncology.

"Over the long term, we hope that being able to decode the sequence of tumours on a routine basis will eventually lead us to being able to better predict which combinations of medicines to use when treating a cancer. We're not quite at that point yet."

The team found 32 mutations after it had spread, nine years after the original biopsy of the lobular breast cancer, which accounts foreight to 15 per centof all breast cancers, Aparicio said.

Power and speed of sequencing

Historically, it has been assumed that tumours are uniform, with the same mutations found in all tumour cells. But only five of the mutations were found in all of the tumour cells, which showed not all cells in a tumour contained the same mutations.

It's now thought that these differencesmay help explain why some tumours resist treatment,Aparicio said.

The researchers used a miniaturized version of DNA sequencing technologies, which allowed them to study the mutations more cheaply in a matter of weeks. Whenthe human genome was initially decoded in 2001, it took years,hundreds of millions of dollars, and a floorfull of machines, compared witha single instrument for the next-generation sequencing used by the B.C. team.

The team hopes their findings will help pinpoint which mutations make cells resistant to therapy and reveal which drugs are most effective for a patient's cancer a step toward personalized medicine, compared with the scattershot approach that doctors use now to treat patients.

"It unlocks a lot of the secrets, if you will, behind cancer development, and equally importantly, the risk of cancer progression recurrance," said Dr. Daniel Rayson, a medical oncologist with the QE II cancer care program in Halifax.

Next, the researchers plan to build a DNA sequencing map of 2,000 cancers from hundreds of patients' tumours, focusing on triple negative breast cancers that are particularly aggressive and have fewer treatment options.

The study was funded by the BC Cancer Foundation, Canadian Breast Cancer Foundation, BC/Yukon region, Canadian Institutes for Health Research, Genome Canada, Genome BC, the Canada Foundation for Innovation, the Michael Smith Foundation for Health Research and the National Cancer Institute, USA.