The breast cancer gene BRCA and IVF
Genetics and breast cancer, what do we need to know?
What is a gene?
A gene is described as the “unit of inheritance”. What it actually refers to is a region of our DNA that codes for a specific protein. In other words, it is a page in our DNA instruction manual.
Our DNA code, made up of genes, arranged in chromosomes, contains the instructions to build our bodies and keep them functioning.
All the inherited traits we have are passed down through our genes. We inherit our genes from our parents and pass some of them down to our children.
We inherit two copies of every gene, one from each parent, passed down through egg and sperm. Since each parent only passes down half of their DNA (containing half of their genes) to each child, any of a parent’s single genes has a 50% chance of being passed down to a child.
What is a BRCA gene?
BRCA is a name derived from the abbreviation “BReast CAncer gene”. Two different genes have been found to influence a person’s chance of developing breast cancer (BRCA1 and BRCA2). We all have copies of both the BRCA1 and BRCA2 genes.
Normal copies of these genes actually do not cause breast cancer. The proteins they code for actually play an important role in preventing breast cancer.
Mutations in the BRCA genes which cause them not to function properly in the body are associated with an increased risk of developing a breast cancer.
The BRCA genes are tumour suppressor genes. Their role is to help repair damaged DNA in our cells. This prevents cells from going rogue and turning into a cancer.
In people with a BRCA gene mutation, when their tumour suppressor gene does not work properly, when during cell divisions other genes becomes broken or damaged, this is not repaired properly. The cell acquires a gene mutation.
How common are BRCA Mutations?
1 in 400 people or 0.25% of our population carry a BRCA1 or BRCA2 mutation. It is more common in people of Ashkenazi Jewish background due to founder mutations that arose and were passed down in ancient communities (1 in 40, 2.5%).
People with a BRCA gene mutation are more likely to develop breast cancer. 5-10% of women diagnosed with breast cancer are found to have a predisposing mutation of the BRCA gene.
How common is breast cancer?
1 in 8 women (12%) will develop a breast cancer before the age of 70 years. It is a common condition and often occurs by chance.
Women (and men) who carry a BRCA gene mutation are much more likely to develop breast cancer before age 70 years than the rest of our population.
BRCA1 mutation risks
We estimate that 55 – 65% of women with the BRCA1 mutation will develop breast cancer before age 70 years.
40 – 60% of women with a BRCA1 mutation will develop ovarian cancer before 85 years.
BRCA2 mutation risks
We estimate that 45% of women with a BRCA2 mutation will develop breast cancer by age 70 years.
15-30% of women with a BRCA2 mutation will develop ovarian cancer before 85 years.
Women with a BRCA mutation who survive and overcome breast cancer are more likely to suffer a cancer relapse/recurrence or a second cancer.
BRCA mutation positive women often develop breast cancers that do not express hormone receptors for estrogen, progesterone or HER2 (triple negative cancers), meaning they are not able to benefit from therapies that target these receptors. With fewer treatment options, “triple negative” breast cancers can be more aggressive and harder to treat.
Men with BRCA gene mutations are at increased risk for a range of cancers, including breast, pancreatic cancer and melanoma (also true for women with BRCA mutations).
I found out I have a BRCA mutation. What can I do?
If you have learned that you have a BRCA mutation, the knowledge is likely to be scary and alarming. However much can be done. Medical, surgical and screening options are available for early breast cancer detection and disease prevention.
If you have been diagnosed, you have likely seen a clinical geneticist who has guided you through testing. Perhaps you or a close relative has been diagnosed with breast or ovarian cancer. The circumstances surrounding diagnosis can be very overwhelming. However, this does not mean you cannot start a family.
If you have been diagnosed with a BRCA mutation and have not yet completed your family – you need to see a fertility specialist for advice.
What can we do in IVF to avoid passing down the BRCA gene?
IVF has come a long way in the last 30 years and it can open doors to using really exciting and sophisticated technology to prevent having a baby with a genetic condition. In the case of BRCA mutations, carriers have 2 copies, one normal, one mutated. We each give only one copy of each gene to each sperm and egg cell that we make. Therefore, when sperm and egg combine to make embryos, in a couple at risk of passing down a BRCA mutation, 50% of embryos will be unaffected.
IVF allows us to take sperm and egg outside of the body to make embryos. We can then biopsy embryos (take a sample of their cells) and test each one for the BRCA gene mutation. We can then choose to only put back embryos that have a normally functioning copy of the BRCA gene to make a baby.
The technique involved is known as monogenic preconception genetic testing (PGT-M). It used to be called PGD (preconception genetic diagnosis).
Pregnancy is achived by placing a normal embryo back into the mothers womb (uterus) where is can implant and grow to make a baby with a normal baseline population lifetime risk of developing a breast or ovarian cancer.
Choosing PGT-M is a popular choice for couples who learn they are at risk of passing down a BRCA gene to their future children. IVF is generally very successful in couples who do not have an underlying disease factor causing infertility and choosing healthy embryos allows families the reassurance that future generations need not be at increased risk of developing cancers.
Written by Dr Raelia Lew
RANZCOG Board Certified CREI Fertility specialist, Gynaecologist and the Director of Women’s Health Melbourne.
Co-host of the Knocked Up Podcast, Co-founder of Ellechemy intimate wellness solutions. Raelia has a PhD in Preconception Health Promotion and Genetic Screening. Raelia is a leading Australian expert in IVF and egg freezing, pioneering a bespoke model of care.