Women’s cancers: Can you change your risk?

Penny Webb: 
Hi, Clare. Thank you.

Clare Blake: 
First of all, what is ovarian cancer?

Penny Webb: 
So ovarian cancer, as the name sounds, is a cancer that appears to originate from the ovaries. But we now know that many of the cancers may not actually start in the ovaries. They might start in the fallopian tubes, which are the tubes that lead from the ovaries to the uterus, and they might spread from there to the ovary. But for all intents and purposes it’s the same cancer, and mostly it’s called ovarian cancer.

Clare Blake:
And the stats for Australian women as they are now?

Penny Webb:
So currently about 1300 women are diagnosed with ovarian cancer every year in Australia, and about a 1000 women will die from the disease. So overall it’s about the 11^th most common cancer in Australia. Although the numbers compared to other cancers are relatively low – so for example, there are about 20 000 women diagnosed with breast cancer every year, that’s many more – we know that survival from ovarian cancer is much worse than for something like breast cancer. So for ovarian cancer, only about four or five out of every 10 women diagnosed with ovarian cancer will still be alive five years later compared to about nine out of 10 of every women diagnosed with breast cancer.

Clare Blake:
And how do they compare worldwide?

Penny Webb:
Interestingly in Australia and also in New Zealand, the rates here are a bit lower than a lot of other high-income countries, so countries like in Europe and North America. The opposite is true for Africa and Asia, where the rates tend in most cases to be much lower than they are here.

Clare Blake:
Do we know of any factors that would increase the risk of ovarian, uterine or breast cancers?

Penny Webb:
So the first thing to say is that all of these cancers have a genetic component. So for example, a small proportion of women will have a mutation in one of the, what are called the BRCA genes… And these women have a much higher risk of developing both ovarian and breast cancer. There’s also another group of genes that increase a woman’s risk of getting uterine cancer and also bowel cancer. So these women do have a very high risk of getting these cancers, but it’s important to mention that the mutations are quite rare, so they don’t affect most women in the population.

Clare Blake:
For ovarian and uterine cancer, we know that pregnancy, breastfeeding, those things have an influence?

Penny Webb:
Yes, we’ve known for a while that things like pregnancy, so the more children a woman has, the lower her risk of getting both ovarian and uterine cancer. The same seems to be true for breastfeeding. So if a woman breastfeeds her children her risk is lower, and also taking the oral contraceptive pill seems to have a very big effect. And I think the important thing to note for these things as well is that while a woman may have her children in her 20s, 30s, perhaps 40s now. She’ll take the pill in again, her 20s and 30s. Doing this protects her against getting ovarian and uterine cancer for many decades after that, well into her 60s and 70s. The tricky thing is that although having children also seems to reduce a woman’s risk of getting breast cancer, it seems that taking the oral contraceptive pill may slightly increase the risk of breast cancer just while a woman’s taking it.

Clare Blake:
Not after?

Penny Webb:
It seems that once she stops taking it, then the risk returns to normal pretty quickly.

Clare Blake:
Penny, where does hormone replacement therapy fit? Because there’s been a lot of discussion about that.

Penny Webb:
So that’s a really interesting question. We’ve known for many years, decades that taking ooestrogen on its own can increase a woman’s risk of developing uterine cancer. And for that reason, a doctor normally wouldn’t prescribe oestrogen to a woman who still has her uterus, so if she hasn’t had a hysterectomy. But we also know that if you put a progestin with the oestrogen and she takes combined oestrogen plus progestin hormone replacement therapy, that doesn’t increase her risk of uterine cancer, and it may actually reduce it a bit. And it seems that the same is true for ovarian cancer, that taking this combined hormone replacement therapy or HRT might reduce a woman’s risk of developing ovarian cancer. Unfortunately, it seems the opposite is true for breast cancer.

Clare Blake: 
Of course.

Penny Webb:
Whereas taking oestrogen on its own seems to be fine, taking the combination oestrogen plus progestin seems to increase a woman’s risk of developing breast cancer. There’ve been some, couple of big trials that have shown this, but it’s important to remember that these trials were done in women who were mostly older and they took the hormones for quite a long time. So it’s not necessarily the same situation as a woman who perhaps has menopausal symptoms and is faced with the question of whether or not she should take HRT. And in that situation I think it’s up to a woman to talk to her GP. Because all women are different, she needs to have a conversation about what is best for her.

Clare Blake:
If it’s unmanageable, then the benefits might outweigh the risks?

Penny Webb:
Yes. If a woman has really bad menopausal symptoms, then for her the benefits may greatly outweigh the risk of a possible slight increase in breast cancer risk.

Clare Blake:
We know being as healthy as possible, for example, obesity is a really important risk factor isn’t it Penny?

Penny Webb: 
So obesity is very important for uterine cancer. Again, we’ve known for many years that if a woman is obese, she has a much higher risk of developing uterine cancer. And a lot of women who develop that type of cancer are overweight or obese. It’s probably also important for the other cancers. So obesity seems to increase a woman’s risk of getting breast cancer after she’s gone through the menopause, and also to a lesser extent it will increase her risk of getting ovarian cancer. But the big link really is between obesity and uterine cancer.

Clare Blake:
What do you know about women that are more physically active?

Penny Webb:
So physical activity is good. It’s the opposite of obesity in many ways. There’s fairly good evidence now that women who are more physically active probably have a lower risk of developing endometrial cancer, probably a lower risk of breast cancer and possibly also for ovarian cancer too.

Clare Blake:
So why does ovarian cancer have poorer outcomes than the common cancers like breast cancer, for example?

Penny Webb:
Probably the main reason why the outcomes for ovarian cancer are not so good is that a high proportion of women, that their cancer is not diagnosed until it’s an at an advanced stage. So it’s already spread to other parts of the body. And that just makes it much harder to treat. So for most women we know that they will have a good response to their treatment initially, but that ultimately the cancer will come back. At that point, it can be much harder to treat.

Clare Blake:
Its locational really, isn’t it? It’s hard to find them.

Penny Webb: 
So that’s certainly one of the reasons why cancers are diagnosed late I think. Firstly, as you say, they’re inside the body. So it’s much easier to detect a lump in the breast or to do a pap smear or the new HPV DNA test for cervical cancer than it is to look at the ovaries. And the other thing is that there are no very obvious symptoms that are associated with ovarian cancer and some don’t seem to have any real symptoms at all until they’re quite advanced. So they don’t immediately suggest that a woman might have cancer. The problem then for a GP or a doctor, if a woman has these very vague symptoms – that might be things like abdominal swelling or pain, possibly changed bowel habits – because ovarian cancer is quite rare, it’s much more likely that the symptoms are for something else and not ovarian cancer. And that just makes it very hard for doctors to know which of the small number of women are who might have ovarian cancer.

Clare Blake:
So does that lead into a little bit why we don’t have a screening process for ovarian cancer for women?

Penny Webb:
So I think there are a number of reasons why we don’t have a screening test for ovarian cancer and unfortunately I suspect it’s unlikely we will have one in the near future. So one of the reasons is that we just don’t have a good enough way of detecting ovarian cancer at the moment. So doctors will do ultrasound tests and they can spot a tumor on the ovaries, but it’s not always obvious whether it’s a cancer or a benign tumor. And we also know that some cancers just don’t show up well on an ultrasound. So a negative ultrasound doesn’t necessarily mean there’s nothing there. There’s also a blood marker called CA 125. But again, this can be high for a lot of reasons that have nothing to do with cancer. And again, it can be low or can be normal in women who do have cancer. So both of these things can be helpful for diagnosis when a woman is suspected of having possible ovarian cancer, but they’re not things that we can use for screening at the population level yet. There have been some big trials where they’ve tried doing this, but the results from them certainly haven’t proven as yet that it’s beneficial to use these to screen women for ovarian cancer.

Clare Blake: 
Well, there’s really only one way to be certain if a woman has ovarian cancer and that’s pretty intrusive, isn’t it?

Penny Webb:
Yes. I think that’s another issue. If a woman does have an indication that she might have ovarian cancer, the only way to really be sure is through some sort of surgery. And although obviously surgeons are very good at surgery now, there’s always some risk when you’re doing an invasive procedure like that. So to have a population screening test for ovarian cancer, we have to have a test that’s really, really good before we can consider using it. If a test is 99 per cent accurate, which sounds pretty good, it still means that one in 100 times it won’t be right. If we start screening a 100 000 women, that becomes 1000 in a 100 000. So if these women all have a positive test that suggests they might have ovarian cancer, the next step potentially is to do some sort of surgery to check that. And we can end up with a situation where we might find some women who do have ovarian cancer, and that could be very good for them, but we might end up doing harm to a lot more women who didn’t actually have ovarian cancer.

Clare Blake: 
It’s easier to screen other cancers where it’s easy to find out whether they do. So if you have a test for cervical cancer, then it’s easy to test if that’s a false positive or not, isn’t it?

Penny Webb: 
Exactly. If that woman has a positive pap smear or HPV DNA test for cervical cancer, it’s relatively easy to check. If a woman has a positive mammogram, then it’s fairly easy to do a biopsy again to check that.

Clare Blake: 
Are the outcomes improving for ovarian cancer, Penny?

Penny Webb: 
Certainly over time, ovarian cancer, women diagnosed with ovarian cancer do better now than they did for example, 25 years ago. So back 25 years ago, the survival rate at five years [after diagnosis] was only about 36 per cent. So that’s only about one in every three women would live for five years. But now we’re up to about 46 per cent, which means that four or five out of every 10 women will survive for more than five years. It’s still not high. We’re obviously hoping it will keep improving over time with new drugs and new treatment.

Clare Blake: 
What would the current treatment be?

Penny Webb:
For almost all women would be surgery to remove the cancer. And then unless the cancer was very small, most women will also have some form of chemotherapy as well. So now they might do the surgery first and then give women chemotherapy after that. But sometimes they’ll give a woman a few cycles of chemotherapy first to try to shrink the cancer a bit. Then they’ll do the surgery to remove it and then give her the rest of the chemotherapy.

Clare Blake:
And there’s some new treatments that may be given after the chemo as well?

Penny Webb:
So the standard treatment usually involves two different drugs that are given either every three weeks or sometimes weekly now for about 15 weeks. But there are some newer treatments that might be given with the chemotherapy, and then for a period afterwards, to try and stop the cancer from coming back. Some of them can be given to all women. Some are designed more for women who have one of the genetic mutations that we talked about.

Clare Blake:
If you know you have ovarian cancer in your family, is there anything you can do then to lower your risk?

Penny Webb:
So certainly if you have family members, particularly close family members, who’ve had ovarian cancer or possibly if they’ve had breast cancer, or if you have a few relatives with breast cancer – as I mentioned earlier, what are called the BRCA genes increase risk of both ovarian and breast cancer. So yes, if you have close family relatives who’ve been affected, particularly if your mother has been affected, or if you have sisters who’ve been affected, if you have more than one relative who’s been affected, or if they were diagnosed when they were quite young, then it’s possible that you might have a genetic mutation or that there’s a gene in your family that increases risk. So in that case, the thing to do would be to go to talk to your GP, to talk to them about it. And they can advise whether or not you should have genetic testing. If you are, or if a woman is found to have a genetic mutation – and as I said, it’s not very common – but the best way obviously then to reduce risk would be to have surgery to remove the ovaries and the fallopian tubes. But obviously that’s not a decision to be taken lightly.

Clare Blake: 
Still on lowering your risk. Are there any particular foods you should either eat or avoid to lower the risk?

Penny Webb:
I think there’s a lot of interest in whether diet affects cancer. There’s been a lot of research into this field, but it’s a really difficult question to answer because our diets are obviously very varied. We don’t eat the same things every day, we don’t eat the same things every year. Certainly up ‘til now there have been a lot of studies looking at diet and ovarian cancer, but none have really identified any individual foods that seem to be particularly important. So I think really the best message is to eat as healthy a diet as possible. It may or may not reduce your risk of getting ovarian cancer, but it will potentially help prevent a lot of other health conditions.

Clare Blake: 
Yes, exactly. Now you launched the OPAL study, O-P-A-L, to answer a noticeable need for patients post-treatment. What were they really asking for?

Penny Webb:
So we started the OPAL study back in 2012, where OPAL stands for Ovarian Cancer Prognosis and Lifestyle. And the main reason for starting this was, we’d done a big study of ovarian cancer a few years earlier. And women who’d taken part in that study were ringing me up and saying that they’d read information on the internet that eating sugar was bad for cancer or eating soy foods was bad for cancer. And they were asking me for advice as to what they should do. And when I started looking into this, I realised that we didn’t really know, there was virtually no real evidence about whether a woman’s lifestyle after she was diagnosed with something like ovarian cancer might affect what happened to her in the future. So it seemed like an obvious gap that we should try to fill with some research to try and generate good evidence as to what might work, rather than women having to rely on random stories on the internet.

Clare Blake:
I imagine if we had answers that would be quite calming for people who’ve been diagnosed?

Penny Webb:
I think it’s important to have answers. If there are things women can do, they clearly need to know that. But if there are things that probably aren’t going to make a difference, then I think it’s important that they know that too. Some women will change their diet. They might start eating a lot of, taking a lot of vitamin supplements or other nutritional supplements. But if that’s not helping, then we might as well tell them or give them that information, and then they can choose whether or not they want to take them.

Clare Blake:
It’s a big study and it’s ongoing, but is there any early findings?

Penny Webb:
So one thing we have found is that physical activity seems to be important. So the women who were more physically active seemed to do better than women who are less active. We’ve also found that smokers seem to do worse. But importantly, the women who stopped smoking around the time that they were diagnosed with their cancer seemed to do a bit better than the women who carried on smoking. So it seems that…

Clare Blake:
It’s not too late.

Penny Webb:
It’s never too late to stop smoking. We’ve also looked at diet. We haven’t found any real evidence yet that the type of diet a woman eats is important, but that’s something we’re still looking at in more detail. We also haven’t seen any evidence that drinking moderate amounts of alcohol makes a difference, but it’s important to stress that most of the women in our study didn’t drink a lot of alcohol. So all we can say is that if you have a small amount, it doesn’t seem to make a difference. We can’t say anything about women who maybe consume more alcohol. But in general, I think certainly being physically active and stopping smoking may well help. We’ve also found that women report very high levels of anxiety, depression, and often insomnia, and also more worryingly that a lot of them don’t appear to be getting any help or support with this. So that’s an area where we really want to look closer and do more to see if perhaps we can predict ahead which women will have these problems and then potentially we can offer them additional support.

Clare Blake:
It’s such a big study. What are the challenges of running a study like this on ovarian cancer?

Penny Webb:
Running any big study is always a challenge. And for something like ovarian cancer, perhaps more so than others, it’s been a real privilege. One of the reasons for this is just the opportunities we’ve had to talk to the amazing women who took part in the study. We approach them and ask them to take part in research at what’s really a very bad time in their lives. And I’m just always amazed that so many of them agree to help, even though they know it probably won’t help them, they do it because they hope it will help other women in the future. It’s important to say, we just couldn’t do research like this without those women, so we’re forever grateful to them. As for challenges, any study of a disease that’s not that common is harder because it took us about three years to recruit all of the women for the study. We then needed to follow them up for at least five years after they were diagnosed. So that makes it a very long study, and we don’t have results for several years after we’ve started. So for something like this funding is always a challenge, getting enough funding to do what was in this case a national study, and to run it over eight to 10 years is challenging. We were lucky we got a five-year grant to start the funding. And then even more lucky that we got a second five-year grant to finish the study. If we hadn’t got the second grant, then [the] study would have ended up being much smaller and shorter than it was.

Clare Blake: 
How did you recruit them?

Penny:

So we worked very closely with the clinicians, particularly the surgeons who treat women with ovarian cancer. We had nurses based in most of the major treatment centres around the country, and they would work with the clinic staff to identify women for the study. The clinic staff would ask the women if they were happy to talk to one of our research nurses, and if they were, then we tell them about the study.

Clare Blake:
I imagine they’d be very grateful for their daughters and granddaughters and all their family that they might be helping. It’s such a big thing to do.

Penny Webb:
It is. And I really hope that we can put out some information that will be useful for women in the future because yes, these women gave us a lot of their time. They talked to us and filled out questionnaires for us over a period of several years. So we obviously want to make the most of all that information they gave us.

Clare Blake: 
What would be your dream outcome for this research?

Penny Webb:
Ultimately I really hope that our study will lead to women having better quality of life and living longer after a diagnosis of ovarian cancer.

Clare Blake: 
Yes. And this podcast is general in nature. So for your own personal advice, your doctor is always the best choice. If you’d like to find out more about Professor Penny Webb’s incredible body of work, or any of our other research, qimrberghofer.edu.au. Thanks again, Penny.

Penny Webb:
Thank you.