Genetic testing for management of breast cancer

Genetic testing for breast cancer can help to estimate the chance of developing the condition, and can help to alter and personalise breast cancer treatment for the patient concerned.

Leading oncoplastic breast surgeon in Greater Manchester and Wilmslow, Mr Sumohan Chatterjee speaks to Top Doctors all about genetic testing in breast cancer management. He goes into expert detail about its role, the benefits and drawbacks and what factors should be considered when deciding to offer testing to a patient with breast cancer.

What is the role of genetic testing in the management of breast cancer?

The role of genetic testing of breast cancer has expanded quite significantly in the last few years. In the past, when anyone had breast cancer, there was a very narrow group of patients who used to have genetic testing. However, now the rules have been expanded because the accuracy of the genetic testing has improved, the cost has gone down and there are a lot of implications for patients who are genetically positive with the BRCA gene mutation or even a huge area of other tests, like CHEK2, another gene abnormality which has impact on the cancer treatment itself, but also to the rest of the family. 

Let's be clear, only five or even ten per cent of breast cancer cases have a genetic fault which drive the cancer. This means that the majority of breast cancers at the moment are what's called sporadic, so it just happens; there's no genetic link. There's no gene fault which had driven the patient to have cancer. 

What are the genetic mutations that can be identified through breast cancer genetic testing and how do these impact treatment decisions?

What is the implication of the gene testing positive? Let's talk about the common ones, which are BRCA-1 and BRCA-2, which are the two dominant and common genes which cause breast cancer. What it means that, not only the fact that patients have breast cancer now, but the chances of having breast cancer in the other breast in the future is very high. It also means that their ovaries are at risk, so, a management strategy to screen and protect the ovaries needs to be done as well.

It also means what treatment is available for the cancer. From the surgery point of view, if anyone has the BRCA gene mutation, even if the lump can be removed with a lumpectomy, a wide local excision, this doesn't protect the patient adequately from future cancers within the same breast. Also, there's a significantly high risk of cancer on the other breast so the strategy for these patients is that they should undergo the removal of the breast, not only on the side they have the cancer but also on the healthy side. This is what we call a risk-reducing mastectomy. Most times this can be combined with reconstruction.

The second implication of gene-faulty cancers is that there are new chemotherapy agents which have now been approved for use. There's a new medication called Olaparib and its now part of our treatment strategy where we use these medications to treat cancers which have a gene mutation. 

In what situations might a healthcare provider consider ordering genetic testing for a patient with a diagnosis of breast cancer?

What are the rules of testing for breast cancer defects? Again, not everyone is suitable for it. The rules now are; if anyone gets breast cancer under the age of 40, unless it's what we call a grade 1 cancer, everybody under the age of 40 is eligible for breast cancer gene testing.

Next, we come to if someone has had cancers on both sides. We can test them if the bilateral cancer has occurred below the age of 50. Both cancers have to be below the age of 50. 

The third, is what we call triple negative cancers, which means all the three receptors; oestrogen, progesterone or both, they are negative. So, anyone who has a triple negative cancer under the age of 60 should have gene tests. There are other ones, as well, for example if there's family history and a person in the family with a man having breast cancer in the family, someone in the family with breast and ovarian-type of cancer, usually first degree or just about second-degree relatives. First degree means daughter, mum or sister.

Whether they've had triple negative cancers, there's a way of working this out. We can either use computer-based models or we can use what's called the Manchester Scoring System for family history. That sometimes pulls in others patients who aren't into those three categories that we talked about before. Nowadays, it's been streamlined. So, the cancer surgeon who gives you the diagnosis will identify whether you fall into any of these categories. If you do, then the next step is to educate the patient about the testing process, about what the implications if it comes back as positive.

There are very good teaching videos which are available, and information booklets, which have been created nationally and regionally. The patient is offered the test and then spends time watching these teaching videos, spends time with the breast care nurses understanding what needs to be done. If they agree, it's a simple blood test like any blood test as if you were having your haemoglobin checked. The blood sample is taken; it's sent off to the regional lab - and the results come back. The problem we have at the moment is a bit of lag between doing the test and getting the results back. It can take anywhere up between eight to twelve weeks.   

If the patient is going for chemotherapy first, this isn't a problem because by the time the chemotherapy finishes, or even half way through if the test comes back as positive, they can add the extra chemotherapy agents to the treatment plan. The surgery, if they need bilateral, mastectomy or reconstruction, that can be planned. There's a bit of luxury of time where these things can happen. The more difficult situation is when the patient needs surgery upfront. Usually in those cases, what we do is tell the patient: 'Just have the lumpectomy, have the results back and then we'll wait for this result. And if you need more surgery, we'll do it a later date.

What factors should be considered when deciding whether to offer genetic testing to a patient with breast cancer?

There's also a testing part where potentially anybody with breast cancer now can self-test. There are very good quality private tests which are available. One website they are available on, which is very reputable, is called Colour. I know patients who've used them and for these, you don't even need permission from your clinician. Once you get a diagnosis, you can sign up to these websites, pay whatever the fee is (somewhere between £300 to £400 when I Iast looked at it). They send you a swab where you collect saliva from inside your mouth, and you put it back into little package they send you and it goes back, and they analyse it. It isn't a blood test. This gives very reliable results and some patients are choosing to have it done themselves even though they don't fall within the categories specified by the NHS. 

Patients, if they're eligible for it on NHS criteria this is available, this is free. If it isn't available within the criteria and the patient still wants to do it, now this is affordable and available. If you imagine when Angelina Jolie has her gene test done, the average cost was to be somewhere between £3,500 to £4,000. Within a few years and an improvement of technology, it has come down to almost ten per cent of that. 

What are the genetic mutations that can be identified through breast cancer genetic testing and how do these impact treatment decisions?

The common gene mutation which causes breast cancers are BRCA-1 and BRCA-2. However, there are other genes which can cause breast cancer, but what's important to remember is those are the rarer ones and it's possible that those genes cause other cancers more commonly than breast cancer. 

At the moment, what's done on the NHS is what we call a 15-gene panel, and it looks for 15 different gene mutations. BRCA-1 and BRCA-2 are at the top of the list. There are others that are related to the breast, for example there are things called CHEK2 and PALB2. However, there are other genes which are lesser known and less important for breast cancer. What we have to remember is if somebody's going for a private test, there are two levels which are available. The cheaper option is just the BRCA-1 and BRCA-2, but increasingly most companies are offering this whole 15-gene panel.

What are the potential benefits and drawbacks of genetic testing for breast cancer?

The potential benefit for someone who's been diagnosed with breast cancer is enormous. It helps us decide what the appropriate surgery is; does the patient need a local surgery if they're negative, or a more bilateral removal plus reconstruction. So, the operation can change from a lumpectomy on one side where the cancer is, to quite extensive surgery on both sides. This can be life-changing, and also body image issues have to be carefully considered. It also has implications for what treatment is available for chemotherapy purposes. There are certain chemotherapy key agents which have now been shown to be very helpful in reducing future occurrence in patients with BRCA gene mutation. 

Thirdly, this will also implications about the ovaries are looked after. They need screening of the ovary, and they will potentially be offered removal of this ovary in the future after they complete their family for example, or when they feel ready to undergo this operation. This has implications about early menopause if it's done at that stage. It's very important to remember that it's going to change how the body has been looked after in the future. For example, if you have an early menopause then you can have a high risk of osteoporosis. Some of these patients who are hormone negative and are still in their thirties when their ovaries are removed, are very rarely controlled as to where HRT is given so that it doesn't increase the risk of cancer, but it protects their bones and maintains the wellbeing that otherwise menopause would have harmed. 

What factors should be considered when deciding whether to offer genetic testing to a patient with breast cancer?

For the family, it's different. If a family member tests positive, the first-degree relative will have a one in two chance of having the same gene defect. If a family member is positive then the test is offered to other first relatives; sisters, brothers, daughters. They can wish to have that test or wish to have that test at an age they feel they should have it, so we should offer it to teenagers, we should offer to people when they're in a position where something needs to be done. It doesn't mean that if you test positive, we have to test your teenage daughter the next day. It has to be done carefully, using genetic counsellors. At the present moment, there's no implication in getting insurance because this isn't one of those mandatory fields that the insurance company needs to know about when they are considering life insurance or critical care insurance. 

It's also important that it's an extra concern for the family members. For example, 'what is the anxiety level of the sister and the daughter, if you test positive. ' So, all these things have to be carefully considered. It's very important that you have to consider informing your family members that you've tested positive. You can choose not to; it's your decision. You can share it with other people who may be affected by it. Unfortunately, we have seen where the family dynamics are difficult, where a family member thinks that their sister or mother has tested positive but refuses to share that crucial information, there's nothing that we clinicians can help them with. You can understand how this affects the family life, how it affects relationships and therefore it isn't something you should do in a rushed way. You should do it after considering and understanding all these options, and all these training videos and counselling helps you prepare to deal with it if you test positive.

If you test negative, and there's no problem. Most of the time the bar is set on the NHS for you to likely to be negative, so there's still about an 80 per cent chance, even if we offer you the test that you may be negative. It's very important to understand that not everyone we're sending for testing, the majority will come back as negative; that's still not the case. The wider we make the net now; a lower number will test positive. In fact, that's one of the concerns we have; is that if we widen the net further and further, we're going to send people for testing and make them anxious for eight to 12 weeks, thinking they might be positive. That is one of the arguments against widening it. Given the benefits of it, and given the potential to stop cancers happening in the future, it's a worthwhile exercise but a patient can choose not to have the test done. A patient can choose not to share the positive result with the family members as well.    

If you're concerned about family history of breast cancer and require genetic testing, arrange an appointment with Mr Chatterjee via his Top Doctors profile.