Barcelona Statement document
This statement has been prepared by the scientific committee of
the 3rd European breast cancer conference that was held in Barcelona from 19 to
23 March 2002. This follows an open debate by the participants of the
conference at a plenary session on Saturday 23 March. The agenda for this
discussion had been set by the scientific committee following private
discussions where we recognised that there was a pan-European concern about the
future of clinical and translational research for cancer in general and breast
cancer in particular.
2. Breast cancer in europe
Breast cancer is the commonest malignancy amongst women in Europe
and the commonest cause of death amongst women in their middle years. Although
in some parts of Europe, with increasing tobacco consumption carcinoma of the
lung is beginning to catch up or even overtake breast cancer as a cause of
Currently, there are 321,000 new cases of breast cancer diagnosed in Europe
each year and this is associated with 124,000 deaths. The trends in
age-specific mortality across Europe demonstrate remarkable patterns .
These were discussed in detail at a special session set aside to consider the
matter. The data were presented by Professor Sir Richard Peto, following which
there were three separate talks attempting to explain the trends in mortality
according to socio-economic and lifestyle changes, the stage of diagnosis and
improvements in treatment.
Across most of Europe, there has been a steep increase in age-specific
mortality from breast cancer from the early post-war years until the mid-1980s.
This almost certainly can be accounted for by increasing prosperity as the
steepness of the rise was determined by the baseline socio-economic deprivation
in the late 1940s and early 1950s. In addition, lifestyle changes whereby
professional women have been postponing the age of first pregnancy could also
account for some of the rise in incidence and mortality from the 1960s onwards.
Mortality rates started to plateau in the mid-1980s and in many countries
throughout Europe there has been a significant fall in age-specific mortality
between 1987 and the year 2000. The steepest fall, amounting to approximately
30% has been witnessed in the UK .
Explanations for this fall in mortality are complex. It is difficult, if not
impossible to explain any of this fall to socio-economic or lifestyle trends.
Some could be attributed to early diagnosis as a result of the screening
programmes which began to be introduced in the late 1980s and early 1990s, but
they would not be expected to deliver their full potential before the late
1990s. Nevertheless, the breast cancer awareness programmes linked to
mammographic screening may have encouraged many women to present with their
disease at a clinically less advanced stage.
That aside there was a consensus that something like two thirds of the
reduction in breast cancer mortality since the late 1980s can be attributed to
improvements in treatment. It can be no coincidence that the first world
overview of adjuvant systemic therapy was presented to the scientific community
in 1985  and treatments such as tamoxifen for
post-menopausal women and cytotoxic chemotherapy for pre-menopausal women were
rapidly introduced at that stage, which explains why the fall in mortality has
been witnessed across all age groups, not just the post-menopausal women who
are involved in the screening programmes.
Following the 1985 world overview, there have been an increasing number of
multi-centre randomised controlled trials for the treatment of early breast
cancer involving collaborative groups throughout Europe with results that
continue to demonstrate modest, but incremental, improvements. If implemented
these newer modalities of therapy should contribute to a continuing downward
trend in mortality throughout Europe.
There are many exciting new agents and therapeutic strategies that are awaiting
formal evaluation by means of the randomised controlled trial. Yet this very
mechanism, which has proven the benefits of treatment in the past and
contributed to at least two thirds of the fall in mortality over the last 15
years, is under threat by well meaning, but misguided, bureaucratic challenges.
3. The protection of the individual patient from abuse is
the first priority
There has been a long and tragic history of abuse of human
subjects in the name of medical science. This dates back to the Nazi war
criminals and the Nuremberg trials. That so-called medical research was nothing
other than torture and the "science" was so seriously flawed that even out of
all this human suffering, nothing of worth can be retrieved .
To make sure that these tragedies will never happen again, we have had a number
of ethical guidelines pre-eminent amongst which is the Declaration of Helsinki
of the World Health Organization.
Added to that, we must not forget the thalidomide tragedy, resulting from the
inadequate testing of a drug with appalling consequences to new-born babies.
Then again it is essential to protect patient's confidentiality, which might be
at risk by the exchange of notes and clinical details necessary for the conduct
of clinical trials and, finally, there have been some well-publicised examples
of scientific fraud, misleading the public and causing untold harm. The most
high profile of these was the fraudulent trial of high dose chemotherapy in
South Africa  .
These unquestioned abuses of human subjects have to be defended against, but
there is always the danger that the entirely appropriate and well meaning
structures, guidelines and ethical directives might have unintentional
consequences in the future.
It is our concern that the over-reaction to abuses in the past has erected so
many bureaucratic hurdles as to make the future conduct of legitimate clinical
research exceedingly difficult or prohibitively expensive.
4. Obstacles to progress
Perhaps the most obvious obstacle to progress for randomised
controlled trials in the treatment of breast cancer is the process known as
good clinical practice (GCP). Even the term GCP is sinister in the way it has
hijacked the meaning of words to suit bureaucratic needs. There is nothing
about the process of "good clinical practice" that can be taken as guidelines
for the practice of good clinical medicine. In other words, GCP has Orwellian
overtones suggestive of 1984 where the very meaning of words has been distorted
so as to make rational thinking impossible.
Its intention is to protect patient confidentiality, ensure that all the
ethical imperatives have been adhered to and guarantee that no rare, but
important, adverse side-effects of a new therapy will be overlooked. No one can
argue against these lofty ideals, but the reality in practice is making the
conduct of clinical trials according to GCP principles very difficult for the
academic community and prohibitively expensive, unless interpreted liberally.
We would therefore urge the regulatory authorities to constantly revisit these
issues and accept that at present the process is far from perfect. No one would
wish the "law of unintended consequences" to apply, so that the very control
mechanisms to police clinical research end up in extinguishing the flame of
5. Ethical control
No one would dispute that good ethics and good science must go
hand in hand. The original declaration of Helsinki was noble in its intent, but
subsequent versions have tightened controls and made the informed consent
procedures so threatening both to the patient and the scientist so as to
discourage recruitment of the large numbers of patients which are required for
statistical confidence. No one would deny the ethical principle of autonomy and
the right to self-determination, but societies cannot expect to give
individuals their rights without the individual in return shouldering their
It could be argued, therefore, that if patients in the future demand better
treatments than those in the past there is a moral responsibility to act as
equal partners with the clinical scientists in the quest for the cure for
cancer. There is a price to pay for autonomy if it ignores responsibility and
this can be calculated in terms of unnecessary loss of life from cancer in the
The Ethics Committees themselves that have to interpret and administer the
declaration and codes of conduct governing clinical research cannot be
populated by individuals who are mere tokens. The study of medical ethics is a
scholarly subject. It is not intuitive and those who are granted the privilege
of serving on these committees also have the responsibility to acquaint
themselves with the nature of disease, the principles of the scientific method
and an understanding of the philosophical underpinning of medical ethics.
If these Ethics Committees (institutional review bodies) do not accept their
responsibility to encourage the future of cancer research they can be perceived
as obstacles to progress, carrying equal responsibility for unnecessary loss of
life in the future, as those clinical scientists who have abused the trust of
the public in the past.
6. Translational research
As we are entering the era of "molecular medicine", a high
priority is to understand why some patients benefit from the therapies and some
don't. We now have in our hands new and very powerful tools, such as genomics
and proteomics, that should greatly facilitate this task and lead to greatly
improved treatment individualisation in a not too distant future.
But this dream will never become a reality if translational research is not
"facilitated": in other words, individual tumour profiles must be obtained in
the context of clinical trials, analysed in the laboratory and correlated to
The creation of this essential "link" between clinicians and laboratory
scientists can only happen if (1) patients understand its importance for the
advancement of patient-care, (2) physicians are encouraged -and not discouraged
- to devote extra time and efforts in this direction and (3) governments give
financial support to these initiatives, which will not always be viewed as
serving the interests of the Pharmaceutical Industry and, therefore, are better
financed through an independent channel.
A very constructive proposal from Europa Donna representatives and deserving to
be examined in more detail is to incorporate consent for any sound
translational research, whether carried out today or several years from now, in
the clinical trial consent form, as long as it does not involve germline
The practical implication for this would be a simplified consent procedure,
while the very few patients not willing to have their tumours analysed would be
allowed to express this disagreement in a written document.
7. The way ahead
One of the most heartening aspects of the European breast cancer
conferences starting with the first in Florence and culminating in the third in
Barcelona, has been the emergence of EUROPA DONNA, the European Breast Cancer
Coalition as a force to be reckoned with. Led by their President, Dr Mary
Buchanan, and Vice President, Stella Kyriakides, their representatives have
demonstrated a willingness and enthusiasm to be advocates for clinical trials
as well as advocates for the needs of individual patients. In return for their
support, they make the legitimate plea that the patients themselves should be
seen as equal partners and stakeholders in the fight against breast cancer.
We have now reached a very important crossroad in the history of clinical
research for breast cancer which will no doubt be reflected across the whole
spectrum of malignant disease in the not too distant future. The sufferers
themselves recognise that it is in their enlightened self-interest to take part
in clinical trials because patients treated within clinical trials tend to do
better than those treated outside . In addition, the EUROPA
DONNA advocates recognise that as they are beneficiaries of volunteers for
clinical trials in the past, they should contribute to the advancement of
knowledge for the next generation, many of whom might be their own daughters.
It is therefore essential to build on the vision that emerged from the
Barcelona Conference, to set up networks and partnership groups where the
consumer could be involved in the design and the monitoring of the clinical
trial as well as being passive subjects within the clinical trial. EUROPA DONNA
is already advancing well along these lines and has gained further
encouragement from the cooperation and enhanced acceptance at EBCC3.
To achieve this requires an education programme targeted at lay-women,
concerning the nature of science and the nature of malignant disease. Such an
educational programme must target the young as well as the middle-aged.
A similar education programme must also be targeted at future members of ethics
committees and institutional review bodies who will sit in judgment of the
clinical scientists in the future. Last, but not least, the politicians who are
directly or indirectly responsible for the bureaucracy governing drug
development and drug registration must be taught to have a longer vision than
the instant popularity they seek in anticipation of the next election. For a
start, those responsible for "good clinical practice" must revisit this
hydra-headed monster in order to determine how it can be trimmed down in order
to facilitate clinical research, rather than impeding it. We believe that this
can be achieved with absolutely no threat to the patient providing common sense
is allowed to prevail.
In conclusion, this declaration of Barcelona, once more commits
the clinical scientific community within Europe to progress in the search for
the cure for breast cancer. At every step on the way, this quest must ensure
the protection of the individual patient and guarantee that her needs are
predominant, above and beyond the needs of the clinical trial itself. Yet at
the same time, we believe that it is in the enlightened self-interest of the
individual patients to be associated with the clinical trial process and this
is now recognised by the women's advocacy groups themselves.
The way forward, therefore, is to build on the strengths of the past where
Europe has led the world in the discovery of better treatments for carcinoma of
the breast. At the same time, we must recognise the dangers and obstacles to
progress in the future. Many of these obstacles are self-imposed and are the
unintentional consequences of processes introduced to protect the patient from
the abuses that were prevalent in the past.
To achieve this, education has to be the watchword and that is education of the
lay public and the ethics committees as well as education of the next
generation of clinical scientists.
The next watchword is partnership and this partnership must be more than lip
service to an ideal, but a genuine, mutual respect between the clinical
scientist, their patients and the politicians responsible for the bureaucracy
governing the discovery and registration of new therapies. GCP like tax and
death is inevitable in one form or another, but this must not be perceived as
an obstacle to progress and the funding for GCP should not make the cost of the
clinical trial prohibitive. If necessary, it should be funded through tax
revenue from central government rather than being seen as a burden upon the
clinical academic establishment and the cancer charities.
Perhaps part of the solution to many of these problems is contained within the
words of Stella Kyriakides from her EUROPA DONNA plenary lecture on Friday 22
" Life with Breast Cancer has slowly acquired a new meaning - it is slowly
being associated with having a voice, with learning to raise it effectively by
asking the correct questions, by demanding to be given valid and informative
answers, by working hand in hand with all involved, by having hope in new
treatments, by remaining realistic about the seriousness of the disease, by not
forgetting those who lose their lives to it, by looking into the future with
hope. There is no longer "a feeling of despair created by the imagination which
pretends there is a future" as Dubois once said, there actually IS a future. A
future that allows us to enjoy every moment at hand, that allows planning for
millions of moments and thousands of days ahead. I really am not sure that we
are survivors -some of us are patients, some have had the experience- of one
thing I am sure, all of us here today, in this Odyssey, must be and are,
PARTNERS. PARTNERSHIP IS WHAT IS ACTUALLY EMBODIED INTHE ORGANISATION OF THIS
CONFERENCE BY European Organisation for Research and reatment of Cancer
(EORTC), European Society of Mastology (EUSOMA) and EUROPA DONNA. So let us all
work hand in hand, as partners, to make life with breast cancer acquire its
real meaning, achieve its true potential and create a future for every person
faced with this reality."
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http://www.bma.org.uk/ap.nsf June 2002.
"The Statement of Barcelona: The future of breast cancer
research in danger"
M. Baum*, M. Buchanan, J. Baselga, L. Cataliotti, J. Jassem, M.
Piccart European Journal of Cancer, Vol. 38, 2002, Issue 17, 2210-2213
Reproduced with permission from Elsevier Science.