Understanding genetic predisposition to cancer

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Published: 17 Oct 2011
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Dr Ellen Warner – Odette Cancer Center, Toronto, Canada

Medical oncologist Dr Ellen Warner talks to ecancer Managing Editor Prof Gordon McVie about women with genetic mutations predisposing them to breast cancer. In this group there are two types of women, those who have not yet developed a cancer and those who have. The main risk for women without cancer, both who have not yet developed it and who are in remission, is whether or not they will develop a new cancer, especially if they are under the age of 40.

The two options for preventative treatment are either monitoring the individuals or to remove both breasts. The medical consensus strongly encourages the removal of both breasts; however, there are ways to monitor patients effectively through MRI screening.

Patients will decide preventative treatment by evaluating the objective risks, for example the likelihood of another cancer because of their age and the effectiveness of each option. Psychological factors also have a great effect. Dr Warner discusses the importance of informing patients on all of their options and allowing them to fully understand their choices for the next course of action.

Hereditary Breast and Ovarian Cancers Meeting 2011, New York, USA

Understanding genetic predisposition to cancer

Dr Ellen Warner – Odette Cancer Center, Toronto, Canada

Professor Ellen Warner from Toronto, thank you very much indeed for your lecture today and for giving us a résumé, five minutes, on what you were talking about. You were talking about women with mutations and there are two groups of women, obviously those who have not yet got a cancer and there are those who have got a cancer and you were discussing how you manage not only those as individuals but their families and those around about them. Let’s take the easier one, the patients who have had a cancer, is that easier? How are you going to manage them after the cancer?

Well I’m a medical oncologist so obviously I have to treat the cancer but let’s assume we’re done with that, then we have to look at other issues. So one of the big issues in these women is what’s the risk of another cancer, either in the same breast if they’ve had breast conservation or in the opposite breast the risk is even higher short-term. They have two choices, they can have the breasts removed or they can opt for surveillance. There are people that feel very strongly that these women should be told, ‘You must remove both breasts because the risk of getting cancer in the opposite breast is very high,’ particularly if they’ve had the first cancer at a young age, like less than forty. Personally I think it’s something that should be discussed, but it’s not an absolute and there are lots of women who opt to keep their breasts and take their chances and minimise their risk in other ways other than removing the breast, such as having their ovaries removed as soon as they’ve had their children out; such as perhaps taking tamoxifen or an aromatase inhibitor or going on a clinical trial and taking their chances. Of course the most important thing is surveillance with MRI because that will find any breast cancer that occurs at a very early stage in the vast majority of cases.

97% I think you quoted.

Yes, we were well over 90% and if you look at our more recent data it’s more up in the 97%. You have to have really good MRI though and you can see, even if you look at the different groups, not all MRIs are created equal and you need a centre with a lot of experience.

And we had another talk about MRI minus contrast as something for the future.

Yes, which is great because the contrast is expensive and you can’t give it to people with renal failure and so forth.

So the two major options, that is surveillance with the problems that that entails and the costs, psychological and financial obviously, and removal of the breast tissue on both sides. In your experience in Toronto, what are the factors that matter for the patients who are making up their minds? What decides things for them? I know that you discuss things at great length.

One thing is just the objective risk which isn’t the same for everyone. Like I mentioned before, the younger they are when they get their first cancer, the more likely they are to get another cancer at some point during their life. Are they able to have their ovaries out or are they still 28 years old and haven’t had their family and are not able to do that? Is it BRCA1 or 2? In BRCA2 we think that chemoprevention may be more effective with drugs like tamoxifen and so forth. So those are the objective things, but I think psychological factors are at least as important and things like where is the woman in her life: is she single, is she married, does she have a supportive partner, has she had her children or not had her children? There are also factors like their personalities, is this a very, very anxious lady? And different types of anxiety are prominent in different women. In some women the breast cancer is overwhelming, you can imagine a woman whose sister, or particularly if it’s a younger sister, is dying of metastatic disease, these women are hysterical about the thought of breast cancer, they just don’t want to deal with it ever themselves. There are issues like how much does the woman in her head believe she’s going to get cancer. There are women who, despite the statistics, they are convinced they’re going to get breast cancer next week, they just know about it. And there are other women who say, ‘I’m lucky, I don’t get it. I’m healthy, I work out, I don’t smoke, I don’t drink, I eat organic vegetables and I’m never going to get breast cancer. I don’t care about your stupid graphs.’

It’s quite a challenge, however, to present that information in a way that each individual patient understands, given that they come from different educational backgrounds, they may come from an ethnic minority, they may have a language problem, an understanding problem. We’re particularly interested in patient empowerment research in Milan and looking at articles with patient empowerment in the title, over 150 of them, all but five were just information provision. Information provision is not enough, am I right?

Right, well you can give people the information but if they don’t understand it for multiple reasons or don’t take it in for some reason, it’s useless. So we have a lot of immigrant ladies, for a lot of them English isn’t their first language, and it’s really important, first of all, just the basic comprehension, either get an interpreter, ideally someone with medical knowledge, ideally someone from the family with medical knowledge who understands how to communicate with that particular individual. But that doesn’t always happen. You also have to get a feel for the woman, like what is her background, how intelligent, how educated is she? How much is she open to this information? How much is she able to receive without just turning off? The more you get to know your patient the better you’re going to really be able to help them.

Are there tools around that can help with this, or would you welcome developing this sort of tool? Not everybody is a big expert like you.

No, I don’t pretend to be a big expert. I know a lot of people who have worked on various information aids, decision aids and so forth of various sorts – the woman goes through an exercise and looks at her values. I’ve worked with some of these things, I think they cater to a limited number of people but my bias is that the kind of people who do best with these things probably don’t need them.

Good, thank you. And then we were going to talk very quickly about the women who are found to have a BRCA1 mutation as part of a family screen. Somebody in the family has got a breast cancer, an ovarian cancer, they get the mutation detected and then you go looking in the family. How do you handle those women?

Pretty similar to the other ones except their risk of getting breast cancer isn’t quite as high statistically. And they also don’t have the biases of the other women of having been through cancer before. They also don’t have the benefit of having a chemotherapy or tamoxifen, which is different. So again very much going through the risks and going through the woman’s individual biases and personality things and where she is. But what’s really important is to keep periodically exploring these things with the woman, it’s not a one-time conversation and things change. The woman might think screening is wonderful at a certain point and then finally she says, ‘You know what? I’ve had it, I don’t want to do this anymore.’ And that may be from something random like her best friend was just diagnosed with breast cancer and she says, ‘Well she didn’t have a family history, I have a mutation. Oh my God, I got to do this.’

More research needed in this area?

Absolutely, and some of the stuff we heard from Professor Lynch was fabulous. The idea of being able to refine out the risk better, rather than say it’s 50-50 over your lifetime, to be able to say, ‘You’ve got these extra genes that make you at much higher risk than someone else.’ That would be fantastic because then we could also take the lower risk women and they wouldn’t have to worry as much.

Ellen, thank you very much indeed.