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

Norman Swan. Today, are there facts that women should simply not know about
their breasts? Potentially important research into mice breasts which could open
up new avenues for breast cancer prevention. Performance enhancing drugs and
the heart and the implications for athletes and anti-doping agencies. Just when
you thought it was safe to go out, a new and potentially deadly brand of a
meningitis germ is emerging. And a Melbourne specialist whose anger over the
actions of the Trump administration this weekend has made him resign from six
learned scientific journals in the United States. He is Associate Professor Stuart
Marshall, a senior research fellow in anaesthesia at Monash University, and we
should note that these are his personal views, not those of the university or any
hospital he's at. Welcome to the Health Report, Stuart.

Stuart Marshall: Thank you very much.

Norman Swan: So these journals, what were you doing at these journals that
allowed you to resign from them?

Stuart Marshall: Well, in my academic world I'm invited to review papers, and I
do that in my own free time. I review for many journals. I often get two or three
requests to look at papers, and of course we review those before they are
accepted in the journal, and they go into publication.

Norman Swan: So you are resigning from that?

Stuart Marshall: Yes, exactly.

Norman Swan: What was your argument to the journals?

Stuart Marshall: It was initially just symbolic in that a few colleagues and I had
already said that we were going to boycott the US conferences, and I had the
idea of withdrawing my pro bono labour essentially, and just put that out on
Twitter as a letter that I was going to send to these journals to share with
colleagues and decide whether or not they thought that that was a good idea and
whether or not they wanted to do the same.

Norman Swan: And have you had a response from the journals?

Stuart Marshall: Not as yet, not a real response.

Norman Swan: Because it's before they have got to work on a Monday morning
so far.

Stuart Marshall: That's right. One journal sent an automated link to reset my
password, but that was about it.

Norman Swan: So you've done this, and why have you done it? What was it that
annoyed you over the weekend that turned into enough fury to do this?

Stuart Marshall: I suppose we've got to try and find something that we can do
each personally and take responsibility for. And this really is just a small thing,
I'm just retracting my labour…

Norman Swan: Because of? Which part of the Trump…?

Stuart Marshall: Well, because of the immigration policies, because my

colleagues in certain countries and potentially of Muslim religion wouldn't be able
to go to the same conferences, wouldn't be able to participate in science the
same way as I can, as a white middle-class male in Australia.

Norman Swan: I'm just guessing now, but my guess would be that the editorial
groups at the journals and that you resign from would not be hard-core Trump
voters, and therefore you are kind of damaging people who are probably on your
side.

Stuart Marshall: Sure, the risk is that obviously science is under threat at the
moment in the US and it further isolates the US at a time when rejection is really
on the increase. But also these journals are generally owned by societies or
associations that have given an enormous amount of money to these political
parties, including the ruling party now in the US. So I think you've really got to put
your money where your mouth is, if you like, and say I'm not going to support
them with my labour.

Norman Swan: And does this damage your career in any way because you can't
put these journals on your curriculum vitae?

Stuart Marshall: Potentially. The US is really the world's powerhouse of medical

psychology and human factors research, which is where I am based…
Norman Swan: So it's about safety and quality in healthcare, how people behave
in the healthcare system.

Stuart Marshall: That's right. And obviously distancing myself from these
communities might well harm my career. But I think there are more important
things at stake here. That's my opinion.

Norman Swan: There's been a huge debate over academic boycotts, particularly
over Israel, and saying, look, why should you isolate…for example, in the case of
Israel, Israeli researchers who are not necessarily in tune with the Netanyahu
government for the sake of this and actually damage the international flow of
information. Where do you sit with that debate? Not necessarily with Israel but is
that you're actually damaging a greater good, which is the scientific enterprise.

Stuart Marshall: And that's the risk, but there are other journals that are
available, and there are other reviewers that are available within the US. My
action may not be taken by all of my colleagues, there may well be people in
Australia and around the world who want to continue contributing in this way.

Norman Swan: And what do you hope happens? Do you think this is going to be
a movement that spreads amongst medical researchers outside the United
States?

Stuart Marshall: Yes, initially it was just really a small thing that I thought I could
do, just sharing an idea with colleagues, and I now realise it really could have
quite a big effect, that it may well pressurise these societies and associations to
act not only to remove their funding from the organisations…sorry, the funding of
political parties, but also put some pressure on the US government to do
something differently in terms of immigration policy.

Norman Swan: Fascinating. Thanks very much for joining us Stuart.

Stuart Marshall: Pleasure, thank you very much.

Norman Swan: And if you want to join the conversation about this one, go on to
my Twitter handle @NormanSwan, or go on to Radio National's @RadioNational
and express your views. Associate Professor Stuart Marshall is a senior research
fellow in anaesthesia at Monash University in Melbourne.
And you're listening to the Health Report here on RN, ABC News Radio and CBC
radio across Canada.

The Western Australian government has announced that it will fund immunisation
for 15 to 19-year-olds against an emerging meningitis germ called
meningococcus W, or Men W. They've done this because of the rise of numbers
in WA, albeit still small. But Men W is potentially nasty and is in epidemic
proportions in South America where the death rate is claimed to be as high as
28%. And paradoxically Men W may not show itself as meningitis. We'll come to
that in a moment. Someone who studies such infections is Professor Jodie
McVernon who is director of epidemiology at the Doherty Institute for Infection
and Immunity in Melbourne. Welcome to the Health Report.

Jodie McVernon: Thanks Norman.

Norman Swan: So what are the numbers of Men W in Australia, because it is

happening in Victoria as well, isn't it.

Jodie McVernon: Yes, well we certainly have seen an increase in the proportion
of meningococcal cases that are Men W in Australia over the last couple of
years, which is really the basis of the concern in WA at the present time. That
said, we need to put it in context. So back in 2002 when we had an epidemic of
Men C, which was a very serious form of meningococcus at that time, we had
almost 800 cases a year in Australia of meningococcus overall, and last year
there were only about 260 cases around the country of meningococcus total. So
part of the tricky story here is that meningococcus is the bug that causes
meningitis that we are aware of, but they are not all created equal. So they have
these different names. So we talk about Men C and B and W, these are different
subgroups.

Norman Swan: And we immunise at 12 months against meningococcal C.

Jodie McVernon: That's right, and the meningococcal C program was

introduced because of those very high numbers back in the early 2000s and it's
being incredibly successful at pretty much eliminating Men C from Australia.
What we had after Men C was gone was mainly due to a bug called B, so Men B,
which was a different part of the family, but this rise in Men W has only really
occurred in the last few years. And, as you say, it mirrors what has happened in
South America and also in the UK and Europe where similar trends have been
observed.

Norman Swan: Just describe what happens because most meningococcal

infection can either be a rash, a fever, stiff neck, don't like the light, you're
heading for meningitis or septicaemia, but Men W can present as something I
haven't seen since I was a newly graduated doctor which is epiglottitis, which is
where you get a blocked throat infection which can be life threatening, you can
get arthritis. It's not necessarily meningitis that meningococcal W causes.

Jodie McVernon: Yes, there has been this description of atypical presentation,
some people coming in with more of a gastro type illness. So it's something that
practitioners need to be vigilant for. It's also mostly affected in Australia so far an
older age group than classic meningococcal disease, which usually peaks in
young infants and teenage years. And the early cases in Australia were also
mainly in people in their 50s and 60s. So there are a few things about that are a
little bit different, and that's something that obviously is being watched very
closely nationally.

Norman Swan: And do we know why it's emerging? Is it just that it spread from
South America somehow, a bit like other infections go global?

Jodie McVernon: So as I said before, meningococci aren't all created equal,

there's a whole family of organisms that make up this group of bugs. And we talk
about them as A, B, C and W, but that's kind of like saying I drive a red car or a
green car or a blue car. I alluded to the fact that the Men W strain that we are
seeing in all of these countries at the moment is actually a lot more like the Men
C strain that emerged in Europe first in the late '90s and then did come to
Australia and caused quite high numbers of cases here and lead to a vaccine
program. It's like saying is a red or a blue Ferrari more alike than a red Ferrari
and a blue Honda Civic. So the actual underlying core genes and things of the
bugs mean that they behave differently, and the particular family, we call it clonal
complex 11, it's just a name, of this Men W clone that is currently being seen in
Australia seems to be a type of meningococcus that's better at being spread
between people possibly but also more likely than some other types to cause
serious infections.
Norman Swan: Has immunisation caused the problem, in a sense? In other
words, that there is an ecological niche, if you like, for meningococcal infection.
You get rid of C because of immunisation, then B emerges, then C and W and Y,
because there's just an empty space for it to inhabit, a bit like sparrows…you
know what I'm saying.

Jodie McVernon: Look, it's a very relevant question but there's no evidence that
that is actually what's happening here. Overall, meningococcal disease in
Australia was decreasing after serogroup C vaccine was introduced, and that's
because even the B disease has also been slowly declining over time, for
reasons we don't understand.

Norman Swan: Even though that's not part of the national immunisation
schedule.

Jodie McVernon: That's right, so we got rid of C and even B is sort of going
down, but we know from looking at this organism and how it behaves in human
populations over time, that it does do this fluctuating thing over time. It's a moving
target. So a new variant might emerge in a population, it spreads a little bit better,
it has a bit of an advantage over another type. And so it will gradually rise to
dominance in the population. So in America for example in the last decade they
had an increase in serogroup Y meningococcus, for reasons that aren't entirely
clear. That hasn't spread to other countries. In New Zealand in recent history
there was an outbreak of a serious clone of a Men B strain that didn't make it
across to us. So we see these shifts in the bug, it's part of the way it behaves and
the strains shift around over time, and so this is why we just need to be really
vigilant in monitoring what it's doing in order to see what the appropriate
responses are.

Norman Swan: And speaking of appropriate responses, the UK has funded a W

vaccine, hasn't it?

Jodie McVernon: It has. So the UK had already introduced a second dose of

Men C vaccine for teenagers, and when they started to see emergence of this
Men W strain, which spread very rapidly across the whole UK, they were able to
just slot in a vaccine that covers against A, C, W and Y into the spot that they
had for a vaccine there. So parts of South America saw this first and introduced a
childhood vaccine, the UK followed closely after and decided to introduce a
teenage vaccine.

Norman Swan: And WA is doing it in the teenage years, and given it happens in
older people, is that the right time to immunise?

Jodie McVernon: The rationale for doing that, and the UK was very clear about
why they chose to do what they did, is that the peak age at which people carry
meningococci is in the teenage years. And when I say that, most…maybe one in
five teenagers are walking around with a meningococcal bug up their noses and
they are perfectly healthy and fine, and the actual chance of the bug causing
serious disease is very, very small. So we know from studies conducted
overseas that the peak age at which people tend to have this bug up the nose is
in the teenage years. And looking at meningococcal generally, as I said, there is
a peak in under-fives and another peak in the teenage years which people have
related to this very high rate of picking it up. And so for that reason in the UK
program has targeted teenagers, and WA has followed suit in trying to reduce the
people who are spreading the bug around potentially.

Norman Swan: And very briefly, if you're not going to introduce immunisation,
what's the best way of preventing meningitis outbreaks?

Jodie McVernon: I think, you know, 'should we come out of the house' is
probably not a sensible statement to make. This is still a very, very rare disease.
And the main measure for practitioners and for people to be aware of is being
vigilant to a high onset of fever. Meningococcus classically causes a typical rash
and it's a rash that doesn't blanch when you press on the skin. So there's a
famous test called the glass test; if you press on the skin with a glass and you
can still see the spots, that's a rash to go and get checked out very quickly. So
early vigilance and diagnosis is the thing, but other than that, there is no specific
prevention, and at the moment, as you noted, the number of cases generally
across the country are still small, although clearly have had a very dramatic
impact on the individuals and families affected.

Norman Swan: Jodie, thank you.

Jodie McVernon: Thank you very much.

Norman Swan: Professor Jodie McVernon is director of epidemiology at the
Doherty Institute in Melbourne.

Women who have dense breast tissue have about 4 to 6 times the risk of
developing breast cancer, and also a risk of having a breast cancer missed.
Research at the University of Adelaide may have found a cause for high breast
density, and one of the lead investigators is in our Adelaide studio, Associate
Professor Wendy Ingman. Welcome Wendy.

Wendy Ingman: Thank you Norman.

Norman Swan: What is breast density?

Wendy Ingman: Breast density is the bright and white on a mammogram. It has
nothing to do with how breasts look or feel, it's really about how they look on the
mammogram, and women have very variable breast density, ranging from mostly
fatty, which appears mostly black, to very extremely dense, which is mostly
white.

Norman Swan: And originally it was thought, well, this could hide a tumour
because the tumour is white on an x-ray too, so you can't see it in amongst all
the whiteness of the density.

Wendy Ingman: Yes, that's exactly right.

Norman Swan: But there's more to it than that because it's now known to be
associated with an increased risk of breast cancer as well, not just missing a
cancer.

Wendy Ingman: Yes, so it is also a risk factor, a very important risk factor for
breast cancer. And it's very difficult in the early days in the 1970s when scientists
first started noticing this association to dissect out the relative contribution of the
hiding effect of breast density and its risk as well. So it actually took 30 years of
research before breast density was established as an important risk factor for
breast cancer.

Norman Swan: So in this study you were trying to get down to the cause of
breast density, what's going on.
Wendy Ingman: So we wanted to understand the biology behind breast density,
what was causing the breast to become dense and what was driving the
increased risk associated with that.

Norman Swan: And there was a clue from women with breast cancer because
there was this little hormone chemical messenger that was switched on and
seems to be driving inflammation around the tissue of the breast cancer.

Wendy Ingman: Yes, it was actually quite a serendipitous discovery. So my

laboratory is interested in understanding the biology of the breast, and in
particular how immune cells function in breast tissue. And so we were interested
in inducing inflammation in the breast at a very low level to see what effect that
would have on breast cancer risk. And what we actually found was that it was
increasing the density of the tissue as well as increasing the risk. And
concurrently with that research we were also working collaboratively with
researchers at the Peter MacCallum Cancer Centre and QUT to try to dissect out
the different types of cells that were present in high dense breast tissue
compared to low dense breast tissue, and we were finding a lot of immune cells
increased in the high dense tissue. So we put those two findings together and
discovered that it appears that chronic low-level inflammation can actually drive
breast density and the associated risk of breast cancer.

Norman Swan: So that's the way the cart and horse seems to work, be hitched,
if you like.

Wendy Ingman: Yes.

Norman Swan: Now, that's in mice. Is there any evidence that that's what
happens in humans?

Wendy Ingman: So at the moment we have an association in humans. It's not a

direct driver-passenger relationship, but we are seeing increases in the particular
inflammatory protein, CCL2, which is what we used to drive the inflammation in
mice. That is elevated in women or in high dense regions in women's breasts.
And we're also seeing other immune cells elevated as well.
Norman Swan: So it's been known for probably centuries that if you have
chronic inflammation and irritation it can increase the risk of cancer. Is it as
simple as that, that it's just chronic irritation of the ducts inside the breast tissue?

Wendy Ingman: Maybe. There are associations with other types of cancer and
inflammation, but this is the first time we've been able to link inflammation with
breast density and breast cancer risk.

Norman Swan: So, all over red rover? Just give women aspirin? Or what? Or
ibuprofen?

Wendy Ingman: No, not quite…

Norman Swan: But there is an association with women who take low dose
aspirin to prevent heart disease, they seem to get less breast cancer, don't they?

Wendy Ingman: They do, and that is actually quite well established, that long-
term aspirin and some other anti-inflammatory drugs do reduce women's risk of
breast cancer. At the moment that's not a recommended treatment to reduce
women's risk of breast cancer because of the side-effects such as increased risk
of stomach ulcers. But we think with this research we might be able to pinpoint
the women who would most benefit from aspirin or some other anti-inflammatory
through measuring the breast density, and so increase the benefit for those
women that would then overcome those potential risks.

Norman Swan: That's all very well, but my understanding is that the only breast
screening program in the nation to tell people they've got dense breasts is
Western Australia, otherwise it's pretty random. Women by and large are not told
if they have dense breasts.

Wendy Ingman: That's right, yes. So the national position statement for Breast
Screen is that they won't report breast density at this time. They do leave the
door open for potentially reporting this in the future.

Norman Swan: So independent of your findings, which are still early days
because they are in mice, surely a woman has got a right to know, because if
you've got dense breasts you might need extra screening or an MRI scan or
something like that.
Wendy Ingman: Yes, well, it is my belief that women should be told about their
breast density because of the risk in missing a breast cancer on their
mammogram and also because of their increased risk.

Norman Swan: So when you put this to the powers that be, what did they tell
you?

Wendy Ingman: Well, Breast Screen have a position statement which you can
read online. They have some valid reasons for not reporting breast density.
There are certainly reasons that need to be addressed, and I can take you
through them if you like but…

Norman Swan: I think what we'll do is we tried to get somebody on this week but
they were on a plane, we might just follow this up on next week's Health
Report and just find out why in the cool, calm rational way which we always do
on the Health Report.

Wendy Ingman: That sounds like a very sensible approach.

Norman Swan: Wendy, thanks for joining us.

Wendy Ingman: You're welcome.

Norman Swan: Associate Professor Wendy Ingman is at the Queen Elizabeth

Hospital and the University of Adelaide.

Performance enhancing drugs in sport never go away as an issue. Last week

Usain Bolt lost one of his gold medals because of one of the team members in
the 4 x 100 relay came up positive in a reanalysis of samples from the Beijing
Olympics eight years ago. A sports cardiologist and researcher at the Baker
Institute for Heart and Diabetes Research in Melbourne thinks that the current
anti-doping regime isn't focused enough on safety and protecting athletes,
especially when it comes to cardiac side-effects. Andre La Gerche published this
recently in the journal Circulation. Welcome to the Health Report.

Andre La Gerche: Hi Norman, thank you.

Norman Swan: One of the extraordinary things is that…and you are sports
cardiologist, I mean, there is real business for a sports cardiologist because
athletes do get cardiac side-effects independent of drugs.

Andre La Gerche: Yes, they do, and it's becoming an area of increasing interest.
From a public health point of view I think it's very important to stress that exercise
at all levels is extremely beneficial to health. But there is increasing evidence that
there is a little sting in the tail for people doing the highest levels of exercise, and
some types of heart arrhythmias are increased in endurance athletes.

Norman Swan: Such as?

Andre La Gerche: Such as atrial fibrillation, for example, which is the most
common sustained arrhythmias, is 3 to 5 times more common in insurance
athletes.

Norman Swan: So this is where you get a kind of fibrillation, a sort of quivering
of the upper two chambers of the heart, and then you get a very irregular fast
heartbeat, which can lead to heart failure and other problems, and stroke.

Andre La Gerche: Exactly. It's not a cause of sudden death, but it's a very
problematic arrhythmia. More controversially some of the more life-threatening
arrhythmias, there's a lot of discussion as to whether they might be increased,
but they are very uncommon arrhythmias, and I think the jury is still out on these.

Norman Swan: So you reviewed the risks of drugs on top of this that have
potential cardiac side-effects. What worried you when you looked at the
evidence?

Andre La Gerche: Well, it was really stimulated from my research background

being about the arrhythmias in athletes. And at presentations and following up on
my research people would often say, you know, how much of this can be
attributed to drugs? And to steal a line from Julia Gillard, used in a different
context, but I'd often say it doesn't explain everything but it doesn't explain
nothing. The real truth is we just don't know how much of an effect drugs have
had on the cardiac health of athletes because it's very difficult to quantify the
amount of drugs being used by athletes and the type of drugs being used by
athletes.
Norman Swan: And it's not drugs that are necessarily banned.

Andre La Gerche: That's right. My personal anecdotal experience is that a lot of

the discussion about drugs being used are not the classical anabolic steroids and
erythropoietin, which are certainly drugs that probably still are being used. But
the sort of new wave of drugs is often off-label use of drugs, so medications that
are indicated for alternative purposes, maybe stimulants, maybe things that affect
the body's ability to take up oxygen, sometimes analgesic agents…

Norman Swan: Painkillers.

Andre La Gerche: Painkillers. Sildenafil is an example of a medication that is

used for erectile dysfunction.

Norman Swan: Well, the name is Viagra. The anti-doping agency said this is not
a performance enhancing drug and you think it might be. What's going on with
sildenafil?

Andre La Gerche: Well, it's intriguing, I think it highlights the inadequacy of the
idea of whether or not something is performance enhancing because it's a drug
that we had done quite a lot of research on, not in the performance enhancing
space but more on the physiological effects. And there is really quite some
evidence that certainly at altitude, sildenafil and that family of drugs improves
endurance sports performance.

Norman Swan: Just because it's dilates the blood vessels? What happens?

Andre La Gerche: Yes, it dilates the blood vessels particularly in the lungs and
at altitude, during exercise in general but particularly at altitude the body's ability
to push its entire blood volume through the lungs is a bit of a constraining part of
physiology. So by opening that up and making the work easier, then you can
push bigger flows of blood around the body which is critical to sports
performance.

Norman Swan: And if there's an athlete taking notes on the Health Report right
now, is there a risk to this?

Andre La Gerche: That's really the key question because just as there is not
much research done on the efficacy or the effectiveness of various drugs for
sports performance, it's not a field that gets funding or ethics approval, probably
should not, there's very little evidence on the safety of these medications for off-
label use. I have no idea what the safety of sildenafil is in the second week of the
Tour de France, for example, where people are exercising and pushing their
bodies to the absolute extreme. There's very little information on any drug in that
context.

Norman Swan: And you've been asked to look at one drug, the new drug for
heart failure called mecarbil.

Andre La Gerche: Yes, so there has been a lot of stories about athletes taking
this sort of wider class of drugs, inotropes, which help the heart to pump more
vigorously.

Norman Swan: So they are often used in intensive care units, but also
increasingly to get people with heart failure, to get their hearts beating more
strongly.

Andre La Gerche: And at a really basic level I can sort of understand why
people would think this would be good for sport because athletic performance
involves the heart pumping more vigorously. But from a cardiologist point to view
it seems extremely foolish because these are medications that almost all have
pro-arrhythmic or have the propensity to cause serious heart rhythm problems.

Norman Swan: We're almost out of time, so very quickly, if you were in charge of
the world, how would you pivot the anti-doping regime?

Andre La Gerche: So I would try to make the athletic sphere like the rest of the
community. And if you were to serve the community aged 20 to 35, for example,
very few healthy people would be on medications, and the medications they are
on would generally be very simple. And I do not see why it should be different for
athletes, and it would be the safest way for things to be. So instead of having a
banned list and the kind of facade of pretending that we are ahead of the
athletes, I would have a simple and quite small list of medications that are
allowed and everything else would be considered illegal unless there was a
therapeutic use exemption, a clear need for a medication.
Norman Swan: Andre, a fascinating point of view, we'll look forward to the
debate as the next Olympics comes closer. Andre La Gerche, thanks for coming
on the Health Report.

Andre La Gerche: Thank you very much Norman.

Norman Swan: Associate Professor Andre La Gerche is head of sports

cardiology at the Baker Institute for Heart and Diabetes Research in Melbourne.
I'm Norman Swan, this has been the Health Report, and I do look forward to your
company next time.