Early Detection and Mammogram?
The
recent developments in the genetic-testing techniques indicate that the
identification of 'presymptomatic' breast cancers might be possible,
although in terms of economics, there is no evidence that this kind of
screening care, will be feasible. Most techniques of screening care however,
do not save money; they cost money. But they do save lives. Breast cancer
screening, cervical cancer screening and colorectal cancer screening with
molecular techniques will be really costly; and the cost
will escalate exponentially (84) if we move to screen say, three-yearly,
then two-yearly, and then yearly. But
we would also possibly save lives. If we catch cancer in its early stages,
we will prevent a lot of expensive treatment later on, thereby saving money
in the other manner also. The problem is, in order to find the one person
who has cancer, we have to screen several thousand people who do not. That
is why the aggregate costs will be so high relative to the benefits. Apart
from that, as we have already pointed out, the identification of
gene-related marker is one thing, and inevitability of the disease is
another. To complicate matters further,(85)
some genotypes may increase the risk of one cancer but decrease risk of
another.
There are other adverse psychological consequences of presymptomatic
genetic testing also. Someone with a positive result may respond
fatalistically, while someone with a negative result may develop a false
sense of security.(86) Even if
we eulogise the importance to the genetic component, we still do not understand(87) the mechanism of changes occurring there
inside the DNA. It is, of course, expected that one day we shall understand
the underlying mechanism, but till date it is not clear whether
understanding a problem will really teach us how to control it. We
understand sunspots, but there is no question of controlling them. Most
diseases, like coronary heart disease, cancer, diabetes, arthritis and
mental illness have genetic components, but multifactorial diseases
have both genetic and environmental components which contribute in different
proportions (88) in a given patient or family. Thus, in effect the whole
purpose of molecular screening will remain largely either an academic, or a
commercial exercise. Thus any assumption that gene studies in cancer will
virtually eliminate the disease is a false assumption.
What
can we do about early detection, clinically? Most of the time and almost by instinct, we advocate Breast
self-examination [BSE]. Despite all our insistence for breast
self-examination over the past 30 years, we see from our experience that
most women do not do it and the vast majority doesn't do it properly. Even
if they do it properly, is it true that they are helping themselves? A
recent report from the Canadian Task Force on Preventive Health Care,
however, says that BSE should not be taught routinely to women aged 40 to 69
years and there is little
evidence (89) to
suggest it is a useful screening tool at other ages. In other ways, it has
simply increased the rate of biopsies in normal breasts. Unnecessary
anxiety, followed by unnecessary investigations and eventually unnecessary
surgery are all destined to produce a commercially viable project, but that
is the reason why report says that it is proven
(90) that BSE is rather harmful.
Can
we depend on Mammography? let us look at the science of oncology at the
elementary level. One divides into two. That is the basic law of nature, as
that of the cells. One cancer cell divides into two, then four, then eight
and so on and so forth. We call it doubling, and the time taken for one
doubling is called doubling time. A tumor is a sum of cancer cells plus the
normal cells. The cancer cells are descendants of one cell that had
transformed and then doubled for several times. Therefore, the number of
cancer cells can be described by the equation 2n [n = number of
doublings]. If we ignore the normal cells, then 1 cc tumor consists of 1
billion cells, e.g., 230, approximately. On an average, a breast
cancer cell takes 100 days for one doubling [the range being from 25 days to
1000 days]. Therefore, 30 doublings take 8 years approximately [30 x 100
days]. We know that it is theoretically possible for a mammogram to find out
a breast tumor at 1 cc which in effect, means we are already late by 8 years
before we could detect a so-called early breast cancer! If now the tumor is
left untreated and the doublings continue, then by another 10 doublings
[total 40 doublings] the volume of the tumor will be 1000 cc [1000 cc = 1012
cells = 240]. This volume of a breast tumor is lethal.
Thus, when we are to treat breast cancer diagnosed at mammography at the
earliest stage, we are to deal with only 25% of the total life history of
the disease. However, this is only a linear measurement, and one must be
aware that there are many realistic limitations also. In clinical practice,
when we find a breast tumor on palpation, it is about 3 cm in diameter,
containing about 45 billion cells. It has therefore, completed 35 doublings. If this
tumour is still localised
in the breast only, we call it early disease. What difference does it
make if we insist on diagnosing a tumour after its 30th doubling, instead of
35th doubling [e.g., mammography Vs palpation]? The available data suggest
that there is no evidence (91)
to prove that a breast cancer starts spreading only during the last 5
doublings [from 30 to 35]. Therefore, although, mammography has its
utilities as any other investigation, it is illogical to assume that our
newfound ability to observe breast tumors between the thirtieth and
thirty-fifth doublings means that it is a great achievement in terms of
prognosis. Why do we insist on mammography then? It is simply because it is
there! It seems that the proponents of mammography continue
to ride roughshod over scientific evidence, driven by emotional, commercial,
and political compulsions.(92)
And thus mammogram is oversold,(93)
and screening for breast cancer with mammography according to a number
of studies(94, 95)
is unjustified because mortality from breast cancer is not reduced in this
way. Some researchers (96)
even have gone to the extent to say that it is a risky procedure, in that
the compressive force used in order to obtain useable mammograms may be
enough to dislocate and spread any existing cancer cells.
In fact in the UK the force used to squeeze the breast as flat as
possible corresponds to placing twenty 1-kilogram bags of sugar on each
breast. According to these researchers the number of cancer sites can
increase by as much as 80% when tumors are manipulated mechanically in this
way. Dr. I. Mittra of Tata Memorial Hospital in Bombay had estimated
(97) that the cost of mammography was 5-10 times higher than
the cost of physical examination. He has also pointed out that mammography
may cause anxiety in women awaiting their test results and often leads to
unnecessary biopsies and treatments. On the other hand, mammography misses
10-15 per cent of the so-called early breast cancers thus providing a false
sense of security (98).
Women over 40 years of age have long been advised to have an annual
mammogram, while it is seen that only 1
in every 20,000 women (99) screened actually receive a
benefit, it is clear that there is no wisdom in this advice; rather it a
sheer wastage of resources.
There
are other interesting questions also. For example, some researcher
(100) refuse to see breast cancer either a local or a
systemic disease. To them it is not a question of early versus late. Breast
cancer does not necessarily go from 0 to 1to 2 to 3 etc; it may start as 4 or 3
or 2 or 1! Thus, according to these researchers no matter how small the
disease, if it is cancer it has to grow and spread, resulting in an
eventually unchanged statistics of the mortality for breast cancer.
It
appears thus, that there is in fact no reliable, dependable and acceptable
way either for screening, or for early detection of breast cancer. The only
possibility of prevention rests at the public level, therefore. However,
there are scientists who refuse to believe it either. Dr Emil J Freireich, a
pioneer of modern oncology says that Cancer
treatment is always better than prevention.....public health strategies
won't work, prevention strategies that affect individual strategies will
never work. We will always have cancer; it is one of the greatest challenges
to the human intellect.(101)
So, we have been told that we should intensify our search for
more effective treatment. Let us now see our prospect at that level.
Treatment??
Our
contemporary practice is to start treating a breast tumor as soon as we find
it by whatever means. We treat it with surgery and chemotherapy almost
always, in their various techniques and forms; and by radiotherapy and
hormone therapy most of the time. Almost always we tend to impress upon the
patient that this is urgent to start treatment. The medical community raises
many hue and cries as soon as a case of breast cancer is diagnosed in an
advanced state. Sometimes the patients are accused of their ignorance and
callousness and at other times the attending clinicians are castigated. This
is done despite the fact that whether delay in diagnosis at any level really
influences the prognosis adversely is still an extremely debatable
issue (102). This is, of course, not to indicate that any
such delay is desirable, for earlier diagnosis certainly reduces morbidity
and saves money; but at the same time this has to be propagated that breast
cancer is not a medical
emergency (103). Almost always our surgeons come out of the
operating theatre to say that they have 'got it all', meaning, of course,
that they have eliminated the primary tumor. And elimination of the primary tumor
marks the beginning of a prolonged treatment most of the time. At the end of
the day, the women having 'bad' type of breast cancer that we call
'invasive', always remains at 16 times higher risk of dying prematurely than
women without breast cancer. Post operative therapies are important
advances, in that they buy time; and we go on treating most of these
patients with larger and larger doses of anticancer drugs with the hope that
the tumour will die (just)
before the patient does (104). In 1935, 26.2 out of every
100,000 women died of breast cancer. In 1992, the latest year for which
figures are available, the adjusted rate of mortality was 26.2 women per
100,000--the same as in 1935(105),
despite our latest chemotherapy activism. It is true that the journey
through conventional chemotherapy followed by aggressive chemotherapy,
followed by high-dose chemotherapy and marrow transplantation, followed by
even targeted therapy have all resulted in gradually improved response rate
in breast cancer. It is also true that they have excellent role to boost the
quality of life for some time, may be even in terms of years; but the
outcome in terms of mortality remains unchanged, and thus the resultant
benefit remains inconclusive
(106). Response rate alone is a poor parameter in order to
assess therapeutic benefit. For instance, according to conventional teaching
[Cecil's TextBook of Medicine, Ed 18, 1988] the overall response rate in
advanced breast cancer is 75%, whereas the disease-free survival is rare.
The overall survival after having an advanced breast cancer has not improved
during the last 30 years. Even if we take 'response to treatment' as a
useful advancement, we shall have to quantify it; for instance, how long a
particular response is going to sustain. In terms of weeks, or months, or
years, or decades? The novel pharmacological approaches that have developed
during the nineties are already immensely expensive; newer approaches are
going to be more. But do the percentages of response after using these drugs
make their use worthwhile? And moreover, does the period of response balance
the cost involved (107(a)
& (b))? The
answer to both the questions is unfortunately: NO!
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