The high-risk genetic mutation that famously prompted actress Angelina Jolie to have her breasts and ovaries removed is the focus of a major new Kiwi cancer study.

The BRCA1 and BRCA2 genes are found in all of us and are normally expressed in cells of the breasts and other tissue, where they help repair damaged DNA.

But when these helper genes mutate they can boost cancer risk, leaving their carriers about five times more likely than others to develop breast cancer and between 10 to 30 times more likely to develop ovarian cancer.

Like Jolie, whose mother and grandmother died from ovarian cancer, many women found to have the defect choose to pre-empt the threat of cancer with surgery.


For young women it can mean a complete loss of fertility.

While public awareness of the danger is far higher than it was before Jolie's dramatic move, researchers and doctors suspect many Kiwis who should be referred for genetic testing are not.

At the same time, fewer than 10 per cent of the 400 to 500 people tested each year turn out to have a known high-risk mutation, and deciding who should receive genetic testing and interpreting the test results remains a big challenge.

"There's an argument that we may be testing the wrong people," said Evangelia Henderson, chief executive of the Breast Cancer Foundation of New Zealand.

"But also that we have a lot to learn about how genetic mutations actually impact individual and family cancer risk."

One Auckland breast cancer survivor, Beth Chapman, said while her sister had tested positive for a BRCA mutation, her own genetic testing had twice come back negative.

"I just thought that was a bit too much of a coincidence," said Chapman, who recently underwent a double mastectomy.

She has now ordered a third test, which this time would also scan for other associated genes as well as both BRCA mutations.


"I just think being fore-warned is being fore-armed - you want to know what you might be in for, and you want to know for your children."

It's just the issue that will be tackled by a new study that's just been funded by the foundation.

Dr Vanessa Lattimore will draw on the DNA of hundreds of breast cancer patients to explore BRCA mutations, along with other lesser-known genetic variations that Chapman suspects.

The University of Otago researcher seeks to find out how many mutation carriers are being missed under current screening guidelines, and whether genetic testing should be expanded to include other known high-risk genes.

Auckland breast cancer survivor Beth Chapman has ordered a third test to reveal whether she has the high-risk BRCA gene mutation. Photo / Supplied
Auckland breast cancer survivor Beth Chapman has ordered a third test to reveal whether she has the high-risk BRCA gene mutation. Photo / Supplied

From the group of patients in the study, she will determine how many of these individuals carry high-risk mutations, and who among them had been referred for testing under the current testing guidelines.

It still wasn't clear how many Kiwis had inherited a breast cancer-associated mutation but had not undergone genetic testing.

"One of the biggest issues around BRCA testing is finding genetic changes in breast cancer susceptibility genes that have unknown clinical significance," she said.

"The uncertainty associated with these genetic changes can increase the stress levels of the patients and their families."

More than 10 per cent of genetic tests of BRCA1 and BRCA2 undertaken in New Zealand will find at least one of these genetic changes.

It was expected that number would only increase if the screening uptake was also increased and more genes were included in the tests.

"These test results are typically put into the too hard basket, as most clinicians don't have the resources and training required to establish whether they are clinically important," Lattimore said.

"With the advent of new genetic technologies and genetic medicine, there is increasing need for collaboration between clinical scientists and clinicians."

Her study also involved developing cutting-edge tools at Brisbane's world-renowned QIMR Berghofer Medical Research Institution.

"Bringing these skills back to New Zealand will allow me to address those test results in the too hard basket and build the genetic expertise in this country," she said.

"Genetic testing among the general population will increase as costs decline, and as new medicines target specific mutations it's going to be important to identify the patients that will benefit from those medicines.

"As we understand more and more about how genetic changes impact breast cancer risk, we will be able to more accurately identify individuals who are at highest risk."

In a separate study also funded by the foundation, University of Auckland researcher Dr Barbara Lipert hoped to learn why breast cancers develop resistance to new drug Kadcyla.

The drug, targeting advanced HER2+ breast cancer, has been recommended for funding by Pharmac, but with a low priority ranking until further investigations are completed.

While it's been shown in clinical trials to extend the life of a significant number of advanced breast cancer patients, for many others it failed to shrink tumours, and the remainder will eventually develop resistance.

"We believe understanding the genetic basis of tumour response to the treatment is critical," Lipert said.

"Understanding how and why resistance emerges is the key first step in predicting it and ultimately stopping it."

She planned to build on work at the University of Auckland that has already identified several genes that could be factors in resistance to Kadcyla.

"We need to evaluate these findings in a multistage process now," she said.

"This knowledge will help clinicians and patients make informed decisions in choosing the best treatment strategy, bringing us closer to making personalised medicine a reality in breast cancer treatment in New Zealand."