Women who have an identical twin sister with breast cancer are at least three times more likely than average to develop the disease, according to a team of researchers from Cancer Research UK.

Where one twin develops breast cancer at an early age, the other has a high chance of doing likewise, reported Professor Julian Peto of The Institute of Cancer Research and the London School of Hygiene and Tropical Medicine to delegates at Oncogenomics 2002 in Dublin, Ireland.

Their research suggests that inheritance is much more important in the disease than previously thought.

Regularly screening women who are at high risk 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.

Peto's team 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.

"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," said Peto.

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 sister 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 4 percent 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.

"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," Peto said. "It's like a radio alarm clock, with some genes behaving as the timer and others as the volume control."

SOURCE:
Oncogenomics 2002, May 4, 2002, Dublin, Ireland