In most people cancer occurs by chance. Sometimes cancer occurs because of a genetic alteration. Genes are pieces of the DNA code that we inherit from our parents. We each have two copies of every gene – one copy is inherited from our mother and one from our father. Working genes usually protect us from getting a cancer. An alteration results in an increased risk of breast cancer, and other cancers.
What are PARP Inhibitors
Parp inhibitors are a type of targeted (biological) therapy. The most widely used PARP inhibitor is currently Olaparib (Lynparza).
Other PARP inhibitors include, Talazoparib (Talzenna), Rucaparib (Rubraca), Veliparib and Niraparib.
Who may be offered PARP inhibitors
and how they work
PARP inhibitors may be used in the treatment of breast cancer that is hormone receptor positive, HER2 negative with an altered BRCA gene; OR triple negative with an altered BRCA gene.
Targeted (biological) therapies block the growth and spread of cancer. PARP stands for poly-ADP ribose polymerase. It’s a protein that helps cells repair themselves if they become damaged. PARP inhibitors stop the PARP from repairing themselves.
Two inherited altered genes that increase the risk of breast cancer developing are called BRCA1 and BRCA2. Cancer cells with faulty BRCA genes are less able to repair themselves if they become damaged. PARP inhibitors can also help block the cancer cells from repairing themselves and cause them to become too damaged to survive.
Please speak to your oncologist about further treatment with PARP inhibitors, or you can find information on
www.breastcancernow.org
High risk Gene Alterations (30-80% lifetime risk)
BRCA 1, BRCA 2, PALB2
A small percentage of people (approx. 1 in 400) carry mutated BRCA1 or BRCA2 genes. People with these altered genes are more likely to develop certain cancers, including breast cancer. The carrier of these altered genes can also pass this altered gene to his or her children.
When you have already developed a breast cancer, there is an increased risk to your unaffected breast also.
Why am I being offered this test?
You are being offered a test to look for genetic alterations that may have been the cause of your cancer diagnosis.
What are the benefits to me?
Knowing whether or not you carry a gene alteration gives your cancer team more information about your cancer. This can help decisions about the treatments they recommend for you, for example which medications or surgery would be most suitable. It will also give you better information about your risk of developing cancer in the future.
What are the possible results of genetic testing and what implications do these results have for me and my family?
Testing can reveal one of three results –
- No gene alterations are found – This is the most likely outcome, as most women with cancer do not have an alteration in these genes. This means that it is very unlikely that your cancer is caused by an alteration in any of these genes. This would be quite reassuring for you and other relatives as it would indicate that your cancer was less likely to be due to hereditary factors that would put them at high risk of cancer. However there may be other genes that increase the risk of breast/ovarian cancer that we have not yet identified so your relatives may still be at a higher risk than the general population and may qualify for extra screening. No predictive testing will be available for other relatives unaffected with cancer. Very occasionally alterations in other genes can be involved in causing breast or ovarian cancer. If your cancer team think other genetic factors might be involved in your cancer then you may be offered a referral to the genetics clinic to evaluate this.
- A cancer causing gene alteration is found – This confirms that an inherited tendency to cancer is present in the family. Women with breast/ovarian cancer who carry this alteration will have a higher chance of developing a new breast cancer and also a risk of ovarian cancer. Your cancer team will use this information to inform the options they offer you in terms of treatment and on-going management. Other members of the family can have a predictive genetic test to see if they have inherited the same gene alteration.
- A ‘Variant of Unknown Significance (VUS) is found – Very occasionally (<1%) we find a gene change, known as a variant. This gene change of unknown significance may be entirely harmless. This result means the family may still have an increased risk of breast/ovarian cancer due to the family history. You will be offered a referral to the genetics team to discuss this further.
Do I have to have the test?
No, having this test is optional. Your decision will not affect the standard of care you receive from your treating team. Some women decide that they do not want testing for any altered genes so near to their diagnosis of cancer but may choose to be tested at a later date when their treatment is complete.
What if I am undecided if I want to have the test?
You could ask to be referred urgently to the regional genetics team who would be happy to explore further with you some of the pros and cons of testing in your particular situation.
What will happen next if I say yes?
If you decide to have the test, you will be asked to sign a record of discussion form. A blood sample will be required for the test.
How will I receive the results of the test?
The breast family history team will give you the result. They will discuss these results with you along with management options. You may also be referred to the genetics service to discuss the wider family implications. If a negative test is found we will calculate your risk of a primary new breast cancer using the CanRisk assessment tool. This will include advice about future mammographic screening as well as confirming the risk for other family members.