Sep 13, 2018

New breast cancer gene analysis aims to boost precision medicine

Photo of a breast cancer survivor at a Komen walk surrounded by family members in pink

A breast cancer survivor and her family at a 2016 Komen Race for the Cure. Photo: Mindy Schauer/Digital First Media/Orange County Register via Getty Images

In an effort to clear up uncertain breast cancer diagnoses involving mutations of a key gene, known as BRCA1, a team of scientists have used gene editing technology to create and analyze thousands of variations to help determine which are benign or not, per a new study published in Nature on Wednesday.

Why it matters: There's been a lot of research on BRCA1 gene mutations, which are associated with breast and ovarian cancers, but the threat posed by each variant is not always known. This leads to confusion for patients regarding if they should take serious prophylactic measures such as a double mastectomy and/or removal of ovaries to prevent cancer, as actress Angelina Jolie did when she found she had the mutation.

Background: The BRCA1 gene is believed to repair damaged DNA and trigger proteins that act as tumor suppressors. Any mutation in this gene is cause for worry — often, but not always, it indicates a predisposition to early-onset breast and ovarian cancer. The mutations can be genetically inherited.

  • While genetic testing for the BRCA1 variants has been around for years, there's a range of diagnoses, including what's called a "variant of uncertain significance" (VUS), which has a frustratingly unclear prognosis.
"It turns out we can read it, but we don't understand it" after 22 years of sequencing.
— Study co-author Lea Starita, co-director, Brotman Baty Advanced Technology Lab

What they did: The University of Washington researchers used CRISPR gene editing technology to cause 3,893 mutations in part of the BRCA1 gene (mimicking the variant of uncertain significance) and then analyzed how cells responded (either causing disease or staying benign). They then posted these findings for further research and possible clinical use.

"This is a step closer to reaching the goal of precision medicine."
— Lea Starita

While the study authors say the "results will be immediately useful for the clinical interpretation of BRCA1 variants," the National Cancer Institutes' Stephen J. Chanock, who wrote a News and Views piece on the new research in Nature, tells Axios that more evidence-based research is needed to make sure the classifications make sense before it is used in a clinical setting.

"The question is, are we ready to take a single, in vitro test and... [use it] to recommend substantially body-altering surgery?"
— Stephen J. Chanock, National Cancer Institute

"This is an important step toward that, but it doesn't answer it," he said.

What's next: Starita says they hope to continue the same process with the remainder of the BCRA1 gene variants.

Go deeper: Read more on breast cancer treatments and precision medicine.

Go deeper