Breast cancer patients with gene fault at increased risk of disease returning

Women with breast cancer who have inherited a damaged version of a gene called CHEK2 are at increased risk of dying from the disease, a major new study reports.

The international consortium which produced the report, including a scientist from The Institute of Cancer Research, indicated that testing some women with a first breast cancer for CHEK2 could allow treatments to be tailored to their level of need.

The large-scale study analysed data from over 25,571 women with breast cancer, and found 459 with CHEK2 mutations. The team tracked the long-term prognosis of these patients over up to 20 years and an average of six-and-a-half years. Among women with oestrogen-receptor positive breast cancer, the most common type of the disease, those with a CHEK2 mutation were three-and-a-half times more likely to develop a second breast cancer and 1.6 times more likely to die from the disease than non-carriers.

A mutation of the CHEK2 gene affects around one in 50 breast cancer patients of northern or eastern European descent. It does not affect women from other ethnic backgrounds.

One of the study authors, Professor Montse Garcia-Closas, professor of epidemiology at The Institute of Cancer Research, said: “Survival from breast cancer has improved markedly over the past few decades, but there remain some patients who do not respond so well to treatment. Identifying those at greater risk of the disease returning is critical if we are to improve survival rates. This study shows that CHEK2 mutations significantly increase the chances of the disease returning. Now that we know this, we need to carry out further studies to look at ways we can provide specific treatment options for these patients.”

In the research paper, published in the Journal of Clinical Oncology, the authors ask whether women of northern or eastern European descent who have had oestrogen-receptor positive breast cancer should be routinely tested for a CHEK2 fault. They suggest further studies are needed to find out if women with the fault should be offered a preventative mastectomy because of the high risk of the disease returning. In addition, they suggest that affected women could be offered anti-oestrogen treatment, such as tamoxifen, for a longer period than for other patients, because of these patients’ increased risk.

“There are few known genetic factors which influence long-term prognosis among breast cancer patients,” Prof. Garcia-Closas adds. “It is important we understand more about how CHEK2 mutations affect patients. However, we also need to find other genetic factors which help identify higher-risk women.”