- By Dr. Sthabir Dasgupta
'Politics and Economics of Breast Cancer' is an extremely thought provoking and interesting piece by Dr. Sthabir Dasgupta. Dr. Dasgupta is senior oncologist from the City of Joy - Calcutta, he has been practicing oncology in private capacity and is also attached with Barasat Cancer Hospital. Dr. Dasgupta is also a key advisor to www.cancerfundamentaltruth.com. "Political Economy of (Breast) Cancer" was published as a monograph by IASS, we produce here some excerpts.
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.
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!
84. Dr. John Goodman. Health Care Rationing: Government-Created Problems and Market Solutions. PowerPoint Presentation. August 29, 1999 - September 1, 1999.
85. The Leading Edge. Genetic testing - are we ready? The Lancet Oncology, Volume 2, Number 6, 01 June 2001.
86. As Above.
87. Yaneer Bar-Yam. New England Complex Systems Institute. Dynamics of Complex Systems. Beyond the gene centred view of evolution. http://necsi.org/html/book.html
88. Williamson R, Kessling AM. The problem of polygenic disease. Ciba Found Symp 1990;149, 63-70; discussion 70-80.
89. Marilynn Larkin. Breast self examination does more harm than good, says Task Force. The Lancet, Volume 357, No 9274, 30 June 2001.
90. N. Baxter with the Canadian Task Force on Preventive Health Care. Preventive health care, 2001 update: Should women be routinely taught breast self-examination to screen for breast cancer? CMAJ; 164(13): 2001 1837-46.
91. David Plotkin, M.D. Good news and Bad news about Breast cancer. The Atlantic Monthly;; Volume 277, No. 6; June 1996, pages 53-82.
92. I Mittra, K N Naresh. Oncology: Unexpected failures . . . and successes. The Lancet. Volume 350, Supplement 3, 20 December 1997.
93. Breast Cancer Brouhaha: Mammograms Oversold. by Andrea Ravinett Martin. October, 2000. http://www.breastcancerfund.org/ disease_ brouhaha.htm
94. Gotzsche, Peter C. and Olsen, Ole. Is screening for breast cancer with mammography justifiable? The Lancet, Vol. 355, January 8, 2000, pp. 129- 34.
95. de Koning, Harry J. Assessment of nationwide cancer-screening programmes. The Lancet, Vol. 355, January 8, 2000, pp. 80-81 (commentary).
96. Mammography: A risky procedure?. International Health News Database. http://pinc.com/healthnews/mammography.html
97. Mittra, I. Breast screening: the case for physical examination without mammography. The Lancet, Vol. 343, February 5, 1994, pp. 342-44
98. Wright, Charles J. and Mueller, C. Barber. Screening mammography and public health policy: the need for perspective. The Lancet, Vol. 346, July 1, 1995, pp. 29-32.
99. Glasziou, Paul P., et al. Mammographic screening trials for women aged under 50. The Medical Journal of Australia, Vol. 162, June 19, 1995, pp. 625-29
100. Interview. Emil J Freireich: a pioneer of modern oncology . Interviewed by Sue Silve. The Lancet Oncology, Volume 2, Number 8, 01 August 2001.
101. As Above
102. Alan S Coates. Breast Cancer: delays, dilemmas, and delusions. The Lancet. Volume 353, Number 9159, 03 April 1999.
103. National Health and Medical Research Council. Clinical practice guidelines for the management of early breast cancer. Sydney: Australian Government Publishing Service, 1995: 1191.
104. Rethinking on Cancer Research: "Blue-skying the future". Draft procès-verbal of the December 1-3, 2000 meeting, held at the Newton Institute, Cambridge
105. David Plotkin, M.D. Good news and Bad news about Breast cancer. The Atlantic Monthly Company. All rights reserved. The Atlantic Monthly;; Volume 277, No. 6; June 1996 pages 53-82.
106. News. Breast cancer researcher accused of serious scientific misconduct. BMJ;320: 2000 (12 February). 398.
107. (a) Friedberg M et al. Evaluation of conflict of interest in economic analyses of new drugs used in oncology. JAMA, 1999;282:1453-1457. (b) Eichenwald K, Kolata G. When physicians double as entrepreneurs. New York Times, November 30, 1999, p. 1.