HOW LIKELY ARE SISTERS TO HAVE SAME CANCER?

THE Nolans’ story highlights the frightening way breast cancer can run in families.

If your sister has breast cancer, you have a nearly 6.5 times higher-than-average risk of developing the disease between the ages of 20 and 40, and double the average risk after the age of 50, according to a major trial published in 2008.

Most ‘family’ cases of breast cancer are linked to inherited mutations in the BRCA1 and BRCA2 genes.

‘For women who have a faulty BRCA1 gene, the lifetime risk is a 60 per cent to 90 per cent chance of developing the disease,’ says Louise Grimsdell, clinical nurse specialist at the charity Breast Cancer Now.

Without this mutation, the lifetime risk is just over 14 per cent.

But in the case of the Nolan sisters, it is a different faulty gene that is involved. As Anne reveals in these pages (see main story), Linda has a mutation of CHEK2, a tumour suppressor gene, just as Bernie did. ‘Most women with familial breast cancer do have faulty BRCA1 or BRCA2 genes, but a small proportion of women have other genetic mutations that we now know can also raise the risk,’ says Charles Coombes, a professor of medical oncology.

It is thought that around 4 per cent of genetic breast cancer cases are linked to a faulty CHEK2 gene.

The lifetime risk of a woman with a CHEK2 mutation developing breast cancer is up to 37 per cent, and they have a 50 per cent risk of passing the defective gene on to their daughters and sons.

Men with a CHEK2 mutation may be at increased risk for breast and prostate cancers.

In recent years, women have been screened for other known mutations, too, usually if they have a strong family history of breast cancer but test negative for BRCA1 and BRCA2.

What isn’t clear is what proportion of cases are linked to as-yet-unidentified ‘family’ genes, although the vast majority of breast cancer cases are not inherited.

So far, scientists have found that mutations of the PALB2, CHEK2 and ATM genes all increase the risk of breast cancer, as well as BRCA1 and BRCA2, ‘but there could well be more,’ says Professor Coombes.

Any mutation can pass on through families.

CHEK2 mutations can lead to a higher risk of breast cancer, but also colorectal cancer and possibly others.

Meanwhile, a review of the ATM gene, published in the journal Current Oncology in 2018, found that around 1 per cent to 2 per cent of adults in the US had one mutation of this gene, which aids tissue repair, and women who carried this mutation had a 25 per cent greater risk of developing breast cancer. PALB2 mutations are also linked to increased risk of breast cancer. ‘These genes are another part of the tissue repair machinery and can go awry,’ says Professor Coombes. He hopes more women will be able to be tested for a wider range of mutations, not least because this could assist with treatment options. ‘There is no gene therapy yet for breast cancer, but we do know certain drugs are more active in patients who have BRCA gene mutations,’ he says.

But inherited genes are only part of the picture. And it’s not certain that women with these genes will develop breast cancer, says Jayant Vaidya, a professor of surgery and oncology.

‘Even with the faulty BRCA genes, between 20 per cent and 30 per cent of women do not develop the disease; and women with CHEK2 mutations have a lower risk than that, somewhere below 50 per cent,’ he says.

Indeed, increasing age and being female are the two biggest risk factors for developing breast cancer, and there are lifestyle factors that can make a difference, too.

Professor Vaidya add that research is still ongoing into the area.: ‘Hopefully in the future we will be able to combine multiple factors, including lifestyle and environmental, and determine a woman’s actual risk.’