Norman Swan: Hello, and welcome to this week's Health Report with me,

Norman Swan. Today, a radical rethink about asthma treatment and who should
get what. Painkillers to prevent cancer, which one is best? Painkillers to treat
pain, which is the least useless? And the Australian Institute of Health and
Welfare has released the latest statistics on cancer in Australia. Breast cancer is
still at the top, bowel cancer next, followed by prostate and melanoma. And
counterintuitively, while cancer incidence is rising, when you do have cancer you
are less likely to die from it. And hidden in this are some important messages for
us all with no cause for complacency. Here to talk about them and also follow up
on a story that we had on last week's Health Report on breast density and the
risk of breast cancer is the chief executive of the Cancer Council of Australia,
Sanchia Aranda. Welcome to the Health Report, Sanchia.

Sanchia Aranda: Hi Norman, how are you?

Norman Swan: All right. Let's start with breast density which can increase the
risk of breast cancer by 400%, it may explain about one in three breast cancers
in premenopausal women. Last week we had research on which talked about this
and showed it might be related to inflammation. But what we discovered as part
of that is that the only state in Australia to actually tell women they have dense
breasts and be aware of this problem is Breast Screen in Western Australia. And
the national policy of Breast Screen Australia is actually not to even record
whether a woman has high breast density. What's going on, Sanchia?

Sanchia Aranda: Part of the challenge for the breast screen program is that
breast density is actually on a continuum. It includes bright areas within the
breast and white areas. It looks as if the white area relates to the masking of
diagnosis. So it increases the risk that a woman's breast cancer would not be
detected with mammographic screening, whereas the bright area looks like it's
the indicator of increased risk. And so part of getting cancer…so part of the
challenge for the breast screen program is that we currently don't have the
algorithms to actually make those distinctions, and we don't have the capability of
them knowing what it is that you're telling a woman. So just telling someone
they've got dense breasts is not very helpful, there is no guidance for what you
would then do in terms of management. And we desperately need the research
that will back up the kinds of information we have about density now.
Norman Swan: So you're in a state of ignorance. In other words, what you're
saying is that if a woman's got dense breasts, you don't know what to
recommend, you should have ultrasound, you should have MRI, you should have
more frequent examinations, so we just won't do anything.

Sanchia Aranda: Well, there's a lot of things that are actually happening. John
Hopper in Victoria has done some fantastic work looking at how you use digital
mammography to be able to separate out the very bright areas that look as if
they are associated with the increased the risk of getting cancer. There are other
groups that are looking at how you collaborate really to understand what you
should do for diagnosis. And part of the challenge for us in Australia is that the
breast screen program has to be about…it's a one-size-fits-all approach, and this
is going to take much more tailored advice to women. We know that this very
bright area of breast density is probably more important for this very small subset
of women than even something like a BRCA1 mutation. So we want to be able to
develop breast risk algorithms that can be applied to individual women, the
embedding of that within the breast screen program will be very complicated
because it is a population-based program. And so we would like to see
researchers come together and embed the work in the breast screen program,
and for funders to actually see that as a priority.

Norman Swan: Well, it is a priority, isn't it? You compare it to the gene that
causes 10 times the risk of breast cancer, but breast density can increase the
risk six times, so it's not that far off the breast gene.

Sanchia Aranda: Because you think about breast density on a continuum, it's
the very one end of it which is this increased areas of brightness. So it's not a
huge volume of women, so it's very similar that breast screen, because it's one-
size-fits-all, doesn't lend itself to doing this at a population level. We are going to
have to look at how you do risk stratification and model that. And of course from
a government perspective you can imagine the anxiety, that if you have a
different screening interval, say for very low risk women versus very high risk
women, and one of those women gets an interval cancer, if you haven't done the
work appropriately then you can cause more problems than you thought you
were going to fix.
Norman Swan: Just before we get on to the cancer statistics, isn't it a bit
patronising to women thinking that they are better off without this information?

Sanchia Aranda: I certainly wouldn't advocate for that. The problem is we are
not at the moment understanding what information we should be given. So when
the radiologist is now…in WA they are giving back density information, but
there's no indication on that whether this is largely the white areas or the bright
areas, so there's no training of radiologists in how to do that at a broader
measurement. They use a thing called Cumulus, but in fact that's just a broad
measure of breast density. And we don't actually know in WA what people are
doing with that. And there's research going on there at the moment looking at
what are the women making of this information and what are their GPs making of
it because it's coming as static information, not with support for how they would
then advise that woman about what's the best approach to manage their breast
cancer risk.

Norman Swan: Let's move on to cancer stats which came out just before the
weekend, Saturday was World Cancer Day. What are the main messages here
from this?

Sanchia Aranda: So from a Cancer Council perspective, three out of the five top
cancers in women and four of the top five in men are preventable cancers or
cancers that can be diagnosed early in the case of bowel cancer. And so this
reinforces the need for us as a community to take charge of our health, stop
smoking, eat an appropriate diet, limit our alcohol intake, but also importantly to
participate in the national screening programs. 36% of Australians participate in
the bowel screening program. It's one of our top five cancers in both sexes, it's
also one of the top causes of death. We know that 78% of people rescreen if they
get involved in the program in the beginning. So a public awareness campaign
around the importance of bowel screening is urgently needed.

Norman Swan: Why is it so low?

Sanchia Aranda: It's probably two factors. One is that when you get that kit in
the mail there's a yuk factor in it. But also what the community tell us and some
work that has been undertaken in New South Wales is they don't understand
really the importance of bowel cancer in our community. They hear lots about
prostate cancer, they hear lots about breast cancer, lots about ovarian cancer,
and many people minimise or have minimal understanding of the risks that they
have for bowel cancer.

Norman Swan: So they don't realise how horrible a rectal cancer can be.

Sanchia Aranda: Absolutely not.

Norman Swan: And there was some evidence and some federal government
research that GPs are not necessarily giving the right advice, they don't
necessarily believe that the test is worthwhile.

Sanchia Aranda: Certainly from a GP perspective we know that a number of

GPs really say to people you are much better off to have a colonoscopy, and yet
the immunohistochemical test that is used in the bowel screen program is
incredibly sensitive and very accurately able to pick up the early bleeding from
polyps. And so it is about a preventive strategy. We've already got a lot of
problems with colonoscopies wait times and other things in this country. So
participating in the bowel screen program is still the best thing to do.

Norman Swan: And yet here's this cancer report and there's nothing on
treatment, there's nothing on the variations in care. And you and I both know that
your cancer outcome, once you've got cancer, is highly dependent on which
surgeon or cancer specialist you are sent to and, more importantly, which team,
and we know almost nothing about what's happening in the private sector, and
yet a lot of all this happens in the private sector. Isn't this something we should
be getting pretty angry about?

Sanchia Aranda: It's certainly big on our advocacy agenda for the coming period
from the Cancer Council. We must start collecting stage treatment and
recurrence if we are going to really understand who is missing out in this country.
Some work that has been done on New South Wales data shows that the gap
between the haves and the have-nots in terms of cancer outcomes is widening.
We can't understand that until we can understand variations in treatment and
care. So this kind of routinely collected data must be embedded in our system.
We have to be able to share data across states and federal jurisdictions. And
while there has been positive movement from the Australian government in that
regard, we aren't getting enough of that data actually being analysed and
informing how we deliver services.

Norman Swan: Sanchia, thank you very much for joining us.

Sanchia Aranda: My pleasure Norman, thank you.

Norman Swan: Sanchia Arandas is chief executive of Cancer Council Australia.

And you're listening to the Health Report here on RN, ABC News Radio, and
CBC Radio across Canada.

Staying with cancer prevention, it is known that some drugs may reduce the risk
of certain cancers, it's called chemoprevention, and the evidence is strongest in
bowel or colorectal cancer. A research group at the University of California, San
Diego, has brought all the available studies together to see which medication
might be best. Siddarth Singh is in the division of gastroenterology at the
University of California, San Diego.

Siddarth Singh: The most commonly studied medication has been aspirin. The
other medications that have been looked at are calcium, vitamin D, folic acid, the
non-steroidal medications like celecoxib. And all of these medications have been
used in combinations too.

Norman Swan: We should just talk about the people that you are trying to treat
here, because it's not just people off the street, it's people who have already got
polyps or had cancer.

Siddarth Singh: Correct. We wanted to target a relatively higher risk population,

a subset of people who have previously had polyps or colorectal cancer and are
at higher risk for recurrence of those polyps or development of cancer.

Norman Swan: There hasn't been any so-called head-to-head trials where
they've compared these drugs to each other, you then had to go and make some
inferences from studies that had already been done of these drugs individually.

Siddarth Singh: Correct.

Norman Swan: So when you brought together the international evidence from
the available trials, and I think that when you added it all up it was about 12,000
people, what did you find?

Siddarth Singh: We found that the non-steroidal medications such as celecoxib

seemed to perform really well and decrease the risk of high risk polyps by about
63% over the next 3 to 5 years. However, from a safety standpoint these
medications were also associated with a high risk of serious events like
hospitalisation, bleeding risk. So perhaps not applicable to every patient who is at
risk for recurrence of polyps, but may be considered for the highest risk patients.
There needs to be a more nuanced decision of risk and benefit. Contrast what
we found, that low dose aspirin is fairly effective in decreasing the risk of serious
polyps, at the same time it's also a very safe option.

Norman Swan: And what about the others, folic acid, vitamin D and so on, did
they have any effect on preventing?

Siddarth Singh: There was not much that stood out in terms of folic acid by itself
or combined with other strategies. And the same thing for vitamin D. There was
some suggestion that calcium may decrease the risk of all types of polyps, not
necessarily the high risk polyps, but there were also some safety signals which
were a little surprising with calcium. So overall we did not think that calcium
would be a good strategy for the prevention of high risk polyps.

Norman Swan: So did you find what the people who had been looking at calcium
for osteoporosis have found, which is a higher risk of heart attack?

Siddarth Singh: Yes.

Norman Swan: Let's just come back to the non-steroidal anti-inflammatory

drugs. So you talk about celecoxib, which we talked about a couple of weeks ago
on the Health Report, trade name Celebrex. That's one kind of non-steroidal but
the more common ones and the cheaper ones you can get over the counter are
things like ibuprofen or naproxen. Were they just as effective as the newer forms
of anti-inflammatories in preventing colon cancer?

Siddarth Singh: That's a good question. The trials that were included have
basically studied celecoxib and another type of non-steroidal called sulindac.
They haven't necessarily studied the non-specific what they call the COX-1 and
COX-2 inhibitors which is ibuprofen and Naprosyn. I suspect the beneficial
effects are going to be similar, but the safety profile from a bleeding risk
standpoint may be higher with the non-selective.

Norman Swan: So the bottom line is if you've got polyps or you've had bowel
cancer and you want to prevent a recurrence or the polyp progressing to cancer,
then low dose aspirin is just safest option, that's like 75 or 100 milligrams a day.
What about the person who…they may have a bit of a family history of colon
cancer, bowel cancer, and they are thinking, well, why don't I just take low-dose
aspirin every day for cancer. A lot of doctors do that. What's your view on that?

Siddarth Singh: Sure. So there's a lot of accumulating data on aspirin having a

chemopreventive effect, not just against colorectal cancer but other cancers too.

Norman Swan: So Dr Singh, are you taking low-dose aspirin?

Siddarth Singh: I haven't started yet. I'm still in my 30s, but as soon as…I asked
my dad to start taking it. I would also emphasise that colonoscopies for continued
surveillance is important. This strategy does not necessarily replace that part, but
it's probably in combination in the sense somebody who has had high risk polyps
shouldn't just rely on aspirin for prevention which would also continue on
colonoscopies based surveillance.

Norman Swan: Siddarth Singh is in the division of gastroenterology at the

University of California, San Diego. And if you're confused about this
colonoscopy story, this is when you've had cancer or polyps and the colonoscopy
is for follow-up.

Over the last couple of years we've followed research at the George Institute in
Sydney about the effectiveness of common painkillers in back pain. Paracetamol
bombed out, as pretty much did codeine. Now they've looked at the same non-
steroidal anti-inflammatories that Dr Singh was just talking about in relation to
cancer prevention. So what did they find? Were they much chop in back pain?
Here to tell us is Associate Professor Manuela Ferreira. Welcome to the Health
Report.

Manuela Ferreira: Thank you.

Norman Swan: What did you do in this study?

Manuela Ferreira: So in the study we actually reviewed about 35 trials

conducted all over the world, and including over 6,000 patients with spinal pain.
And we are interested in actually assessing or identifying the magnitude of the
benefit as well as the risk of adverse events associated with these drugs.

Norman Swan: And when you say spinal pain, just describe what was
happening to these people on average?

Manuela Ferreira: So basically the common back pain, as well as neck pain and
sciatica.

Norman Swan: That's where the pain goes down your leg.

Manuela Ferreira: That's right, that's when the pain goes down your leg.

Norman Swan: And these were randomised trials, so they were against placebo.

Manuela Ferreira: So all of these trials were randomised trials, and yes, so one
group received the drug, the anti-inflammatory, and the other group received the
placebo or sugar pill.

Norman Swan: So what did you find?

Manuela Ferreira: So what we found was actually…there is some benefit. So

anti-inflammatories, they do offer some benefit compared to placebo, but it's a
small benefit. So on average it's less than 10% what you would get if you just
took a sugar pill.

Norman Swan: So 10% above a sugar pill?

Manuela Ferreira: Above a sugar pill, exactly, less than 10%.

Norman Swan: So would you notice it if you didn't know what you are taking,
would you notice that 10% difference?

Manuela Ferreira: It's a good question. Arguably patients wouldn't really think
that this is noticeable or worthwhile.
Norman Swan: What sort of percentage uplift would you need to notice it's
worthwhile? Because you've done some studies on this.

Manuela Ferreira: We have, yes exactly. So patients believe that they need to
be at least 25% better or above placebo to consider the risks of side effects
associated with anti-inflammatories worthwhile.

Norman Swan: And there are risks of gastrointestinal haemorrhage and things
like that. So after all these years of research, paracetamol, not much good, in fact
I don't think it was any good. Opioids, codeine-like drugs, a bit like the anti-
inflammatories, you got some effect but probably not enough to make a
difference, and where you have constipation or risk of addiction. And here you've
done the same thing with non-steroidals. As a sufferer of back pain, like many
people in Australia, I'm getting a bit depressed now Manuela. Tell me something
that I can do, and why painkillers aren't helping.

Manuela Ferreira: Well, there are many reasons why painkillers wouldn't help.
So, for example, let's look at anti-inflammatories. So the role of an anti-
inflammatory is to reduce inflammation. So one reason could be that they are not
reducing inflammation enough to actually result in a reduction in pain and
improvement in function. Or it could be that inflammation is not the main cause of
back pain. It could also be, like you were saying, that patients don't perceive that
as being worthwhile overall. So, for example, anti-inflammatories and opioids can
give some quick relief. But along the way overall that relief is not really perceived
as being an improvement or don't lead them to recover from their condition.

Norman Swan: So have we misconceived what back pain is?

Manuela Ferreira: It's a good question. We have noticed in research that the
approaches, the treatments that have a broader view, so for example the healthy
lifestyle interventions, reducing your weight, healthy diet, being physically active,
all those approaches, they actually have a better or a greater benefit in the
management of back pain. So yes, maybe we have been looking at…

Norman Swan: Just forgive me a moment of scepticism; what's a healthy diet

got to do with my back?
Manuela Ferreira: Well, healthy diet has a lot to do with your stress, has a lot to
do with maintaining your healthy weight. And that has a lot to do with your back.

Norman Swan: Physiotherapists have developed some…the evidence based

around physiotherapy, chiropractic, it's kind of there. Manipulation might help in
the acute but it doesn't help in the long term. But there has been a recent thing
about core muscle strengthening. Is there any physio that actually helps here?

Manuela Ferreira: There is actually exercise based or physical activity-based

interventions that do help. So exercises strengthening your core, or sometimes
even going for a walk. So all of that has been shown to effectively reduce your
back pain.

Norman Swan: As opposed to just lying down to it.

Manuela Ferreira: Exactly.

Norman Swan: And you're also about to tell me you need more research to find
out really what's going on.

Manuela Ferreira: We do…

Norman Swan: Of course.

Manuela Ferreira: Yes, we do.

Norman Swan: And you're back pain sufferer yourself.

Manuela Ferreira: I am a back pain sufferer myself, yes.

Norman Swan: So physiotherapist heal thyself.

Manuela Ferreira: You know, when I'm in crisis what I personally do, I go for a
short walk, a light walk, and for me it does the trick.

Norman Swan: But people get into sort of bad posture, you've got to really
correct that too, because that can make you worse.
Manuela Ferreira: Yes, so one piece of advice is actually to stay away from
prolonged standing, prolonged sitting, and stay away from activities or positions
that actually aggravate your symptoms.

Norman Swan: Manuela, thank you very much for joining us.

Manuela Ferreira: You're very welcome, thank you for having me.

Norman Swan: Associate Professor Manuela Ferreira who is at the George

Institute in Sydney.

Let's stay with international research coming out of Australia because an

international study led by Australians has found that asthma medication normally
reserved for more severe asthma could benefit children and adults at what used
to be thought of as at the mild end. Professor Helen Reddel of the Woolcock
Institute led the study and she is with us now. Welcome to the Health Report,
Helen.

Helen Reddel: Thank you.

Norman Swan: So just explain the thinking behind this study and what the
before state was, in other words what the policy was for asthma care before you
did this study?

Helen Reddel: This study actually originated out of investigating the evidence
behind guidelines about which patient should receive a preventer inhaler, an anti-
inflammatory inhaler for asthma. We found that over the last 20 years it has been
consistently recommended that you don't need one until you have symptoms
around about more than, say, two or three days a week. We went looking for the
evidence for that and didn't find any in the published literature.

Norman Swan: You're kidding!

Helen Reddel: Yes…

Norman Swan: So this received wisdom is based on nothing?

Helen Reddel: Well, look, I think it links with the concept of asthma that was
around when the guidelines were first written, that asthma was perceived as a
condition of narrowing of the airways that was readily relieved by a short acting
blue puffer such as Ventolin. Since then it has been very well established that
asthma is generally characterised by inflammation, but it seemed as if no one
had actually gone back and looked at the implications at that for who should get
treatment.

Norman Swan: So you've been involved in these large study called START. You
better tell us about that before you…

Helen Reddel: Yes, so we were particularly interested in mild asthma because

that was where the evidence gap was. And after quite a bit of investigation we
found this particular study…

Norman Swan: And just to…because people might get a bit lost…so the policy
for mild asthma, we are talking about both children and adults here, is that if
you're only going to get wheezing once a week or something like that then the
blue puffer is fine, just take it before you go out on a cold day or before you have
exercise. But if you're starting to use it a lot then you might need a preventer, that
was sort of the advice.

Helen Reddel: That's right, yes. So we looked for studies that had recruited
people who had mild symptoms, infrequent symptoms like that, and found this
large study that had been published in 2003 in over 7,000 patients with mild
asthma, children and adults, in which they had been randomised to receive either
a very low dose of a preventer inhaler or a placebo. What we looked at was
whether the frequency of the patient's symptoms at baseline predicted whether
they responded to the preventer inhaler. So we were testing the basis for this
previous assumption about who should get them.

Norman Swan: And this required a reanalysis of the data.

Helen Reddel: That's right, yes.

Norman Swan: So just before we go on, I don't want to get too technical here,
and we've had stories on this before on the Health Report, is that it's kind of a no-
go area reanalysing data in a trial, isn't it, because you are trying to find out
something that the trial was designed to discover.
Helen Reddel: That's a good point. In this case the initiative for doing this
analysis came from investigators like myself. I was involved in updating
international asthma guidelines. So it wasn't driven by the company. And we set
down our question in advance and did an analysis plan in advance. So it was
done with the same level of rigour as if that had been the original question.
Obviously that isn't as strong as conducting a study like this from the start, but it
would be hugely expensive and take a very long time to start a process like that
from now.

Norman Swan: So what did you find?

Helen Reddel: What we found was that regardless of how frequent the patients
had symptoms at baseline, whether it was less than once a week or more than
two days a week, they got a similar benefit from this low dose preventer. It halved
their risk of having a severe flare-up that would take them to the emergency
department or in hospital. It reduced the decline in their lung function and it
proved their symptoms, which were already fairly infrequent in that group. So we
found that there was benefit across the board for people with mild asthma.

Norman Swan: And what sort of numbers did you have to…because it's fine to
say that, but somebody at the more severe end is going to get a severe
exacerbation of their asthma more frequently than somebody at the mild end,
aren't they, and therefore they going to get a higher percentage benefit from
taking the preventer. Or have I misread your results?

Helen Reddel: Well, what we found was that the risk was halved, regardless of
what the baseline…

Norman Swan: But if the risk is low, you've halved it from a low risk, it's half a
small number. It makes you wonder. How many children would have to take the
puffer for one asthma event to be prevented?

Helen Reddel: Exactly, and that's where the debate is at the present because
what this would require would be taking a regular preventer every day when you
perhaps only have symptoms, say, once a week or less. So that's the really
interesting thing about this research, it leads us to say is there something better
than this that can be used in the future to give protection but without having to
take a daily preventer inhaler.
Norman Swan: Such as?

Helen Reddel: Well, various options have been tested but the one we are
investigating at the moment in several large studies is to look at a combination
inhaler that gives you quick relief but it also contains an anti-inflammatory
medication. Looking at that…

Norman Swan: They already exist.

Helen Reddel: That's right. They are only approved at the moment for people
who have more persistent asthma symptoms, who need a regular daily inhaler
and who aren't well controlled with just a low dose preventer alone. So they are
there on the market, safety has been well established. What we are testing is a
new way of using these in people with very mild asthma who just use that
combination preventer and reliever…

Norman Swan: Ah, so instead of taking the blue puffer when you get your
wheezing, you would take the combination and in theory get a bit more kick to it
because you've got the preventer as well as the long acting reliever.

Helen Reddel: That's right, and the key thing about this particular medication
that we are testing, which has a combination of budesonide and formoterol in it,
is that we already know from studies in people with more severe asthma that if
you quickly increase the dose based on your symptoms as you start to get
worse, it markedly reduces your risk of having a flare-up. So there is already a
history with this particular medication to suggest that if you get extra anti-
inflammatory treatment when your asthma symptoms are more, that you may get
greater benefit. But this has to be tested, and we've got some large studies
underway looking at that at the moment.

Norman Swan: The research that you've been involved with in Sydney and also
the thunderstorm asthma event in Melbourne has shown that people, even if they
are prescribed these preventers, aren't taking them.

Helen Reddel: Yes, that's right. So, overall in data from the whole of Australia
from the PBS dataset, we see that fewer than 20% of young adults with asthma
take enough of a preventer to be taking it regularly. And overall probably most
people take about 25% of the prescribed dose. That's clearly far from desirable if
this is something that is going to substantially reduce your risk of an adverse
outcome in the future.

Norman Swan: People say that asthma is a different disease in children. Did you
get different results in children from adults in this study?

Helen Reddel: This study included children from the age of six upwards, and we
didn't see a difference by age group in the reanalysis.

Norman Swan: Helen, thanks for joining us.

Helen Reddel: Thank you very much.

Norman Swan: Professor Helen Reddel of the Woolcock Institute.

You've been listening to the Health Report, I'm Norman Swan, I hope you can
join me next week.