Six sisters impacted by breast cancer gene PALB2

While people across Australia have been grappling with COVID-19, the Kerr sisters from New South Wales have been coming to terms with an unfolding genetic story that has implications for their entire family.

‘It’s been like a freight train through our family,’ says one of the sisters, Jane Kerr. ‘It’s affected six out of seven sisters and our mum – one after the other: test, result, test, result.’

Jane is referring to her family finding out they are carriers of a gene fault that significantly increases their risk of breast cancer by between five and nine times higher than average. But it’s not the relatively well-known BRCA1 and BRCA2 genes. It is a gene called PALB2, which research has shown is just as important in breast cancer risk as the BRCA genes.

‘Our family has a lot of women, some of whom have a history of breast cancer, so we were aware of the BRCA gene testing. My sister Cathy and myself, who have both had a diagnosis of breast cancer, were both tested for BRCA in 2017,’ says Fiona. ‘It wasn’t until my sister Cathy was preparing for her recent breast cancer treatment that we learnt there was another gene linked to an increase in breast cancer risk.’

Cathy has been diagnosed with breast cancer twice now – the first time was in 2012. When she was diagnosed again this year, her original sample that she provided for BRCA testing was retested for PALB2.

The test confirmed she had the gene fault. Since they learnt about PALB2, the family has faced it together. In the two months since Cathy’s test results, six sisters and their mum have been identified as carriers of the gene mutation.

The family wants to share their story to help raise awareness of the PALB2 gene.

‘We were completely blindsided by this and just want to make sure other families out there know about this gene so they can make informed decisions about their breast cancer risk, like we have,’ says Jane.

Fiona recalls her specialist explaining how a genetic fault comes to be.

‘She said to think about it like a spelling mistake in the gene,’ Fiona says.

If one gene has the spelling mistake, it is then replicated in every cell that contains that gene and can also be passed on to the next generation. For the Kerr family, this means 20 children and young adults (15 girls and five boys, ranging in age from 4 to 28 years) can also be impacted by this gene. They can choose to be tested or monitored once they are over the age of 18. There is generally a 50/50 chance of inheriting PALB2, although the odds have proved much higher with the sisters.

It’s been a lot for the family to come to terms with.

The Kerr sisters and their mum are making individual choices about their breast cancer risk. Two sisters, Cathy and Fiona, have had bilateral mastectomies and DIEP flap reconstructions since July. Jane, Meg and Eileen are booked in for risk-reducing surgeries but know these may be delayed because of the impact of COVID-19 on elective surgery cancellations.

Liz and their mum, whose name is also Eileen, have the fault in their PALB2 gene and are currently also considering risk-reducing surgery. Mary is the only sister who is not a carrier of the faulty gene.

The experiences of two sisters who have had surgery are mixed and depended on whether they had private health insurance or went through the public system. Cathy, with an active breast cancer, was booked through the public system for surgery. She found it traumatic when her surgery was cancelled twice because of COVID-19 pressure. She had to find $50,000 to self-fund the surgery in a private hospital with only days notice after the public hospital’s final cancellation. Fiona, on the other hand, went privately and had her surgery as planned, but she is out of pocket $20,000 despite having had a previous breast cancer diagnosis and full health insurance.

The impact of the genetic testing continues to be felt throughout the family.

‘Our immediate family has been affected by breast cancer since 2012 when Cathy was first diagnosed,’ says Jane. ‘There is a lot of suffering that would have been avoided if we had known about PALB2 earlier. We want to make sure other families don’t have to go through what we have.’

PALB2 and other inherited gene mutations

Many people would be aware of the BRCA1 and BRCA2 gene mutations, which for women increase the risk of developing breast and ovarian cancer, and for men increase the risk of prostate cancer as well as breast cancer. These genes and their link to cancer recently reached the mainstream when the actor Angelina Jolie revealed that she carried an inherited BRCA1 mutation and had chosen to have preventative surgery to reduce her risk of developing breast and ovarian cancer.

Researchers around the world have now discovered other inherited gene mutations that increase a person’s risk of developing breast cancer. These include TP53, PTEN, CHEK2 and PALB2. In the future it is likely even more genes that may increase an individual’s risk of breast and other cancers will be identified.

Inherited gene mutations are passed down through families and can be passed on by either the mother or the father. Affected families often have several members across generations who have had breast, ovarian or prostate cancer.

While these genes are very important, most women who develop breast cancer do not have a strong family history and only five to ten per cent of all breast cancers are the result of an inherited gene mutation.

When these genes are working properly, they help to protect against cancer. When there is a fault, they can increase the risk of cancer.

Everyone has two copies of the PALB2 genes (one from their mother and one from their father). Under normal conditions PALB2 helps to protect against breast, ovarian and pancreatic cancer. When one of the copies is not working properly, this is known as having a faulty PALB2 gene, or a PALB2 mutation.

Women who have a faulty PALB2 gene have about a 55 per cent chance of developing breast cancer and about a 5 per cent chance of developing ovarian cancer over their lifetime. They can also pass the gene onto their children, with each child having a 50 per cent chance of inheriting the faulty gene. BRCA1 and BRCA 2 work in a very similar way, but women with a faulty BRCA1 or BRCA2 gene have about a 70 per cent chance of developing breast cancer.

All states and territories in Australia have family cancer clinics offering specialist genetic services to individuals and families concerned about cancers in their families. Genetic counsellors and specialists provide advice and care to such families. To find a family cancer clinic near you, you can telephone the Cancer Council on 13 11 20 or go to cancer.org.au and use the search function.

Issue 89
Spring 2021