Triple risk for breast cancer twins

Women who have an identical twin sister with breast cancer are at least three times more likely than average to develop the disease, a leading Cancer Research UK scientist will tell fellow experts.

Where one twin develops breast cancer at an early age, the other has a high chance of doing likewise, Professor Julian Peto reports at a prestigious conference in Dublin¹.

His research – along with recent evidence from colleagues funded by the charity – suggests that inheritance is much more important in the disease than previously thought.

Screening women who are at high risk regularly could help save lives from the disease, while understanding the genetic causes of breast cancer is vital if scientists are to develop new treatments.

Identical twins are so-called because both siblings have exactly the same genes. By studying twins, scientists can assess the importance of inheritance in diseases like cancer, since if one identical twin has a high inherited risk, so will the other.

Prof. Peto, who divides his time between The Institute of Cancer Research and the London School of Hygiene and Tropical Medicine, analysed US data covering 1,300 pairs of identical twins and 1,000 pairs of non-identical twins, where one twin had already developed breast cancer. The unaffected twins were followed for several years afterwards to find out how many also went on to develop the disease.

He found that at least one-third of the identical twins were destined to develop breast cancer at some stage in their lives, compared with just one-ninth of women in the population as a whole.

Non-identical twins of breast cancer patients had a much smaller risk of the disease. This suggests identical twins gain their increased risk by inheriting the same set of genes as their sister with cancer, rather than through sharing the womb, or being brought up together.

Prof. Peto says: “If a woman’s identical twin has breast cancer, her shared genes will mean she has a high risk of the disease too. We now think that many – possibly the majority – of breast cancers occur in a minority of women with an inherited risk. Identifying and monitoring these susceptible women is going to be an important challenge.”

Prof. Peto’s study also showed that where one twin developed cancer at an early age, the other was likely to follow suit. Of women whose twin sisters had developed breast cancer before the age of 40, a quarter went on to get the disease in the next 20 years. By contrast, only four per cent of the female population as a whole developed breast cancer before the age of 60.

Strangely though, twins of women diagnosed before the age of 40 were at no higher risk of breast cancer in later life than twins of patients diagnosed after age 50 – their risk just increased at an earlier age.

Prof. Peto adds: “It’s all rather puzzling, but it seems breast cancer genes are doing two different things. Some genes seem to act as timer switches, determining when a woman’s risk of breast cancer should begin, while other genes dictate how big the risk will be.

“It’s like a radio alarm clock, with some genes behaving as the timer and others as the volume control.”

Faulty versions of the BRCA1 and BRCA2 genes are known to greatly increase the risk of breast cancer, but these only account for about two per cent of cases. Inherited risk is probably more often caused by a combination of genes, each with a modest effect.

Two weeks ago, scientists from The Institute of Cancer Research and Cancer Research UK’s Epidemiology Unit in Cambridge reported the discovery of one such gene – CHK2.

Sir Paul Nurse, Interim Chief Executive of Cancer Research UK, says: “We’re seeing a significant expansion in our knowledge of breast cancer genetics at the moment, and Professor Peto’s work is providing some valuable insights.

“Knowing that the identical twins of women with breast cancer have such a high risk is of practical use, since we can carefully monitor and counsel these women more effectively. The research will also play a vital role in clarifying our picture of how the disease develops and particularly how a woman’s genes can combine to increase her risk of the disease.”

ENDS