Era of Hope 2011 Plenary Sessions

Session Title: Morning Session – The State of Science

Title of Presentation: The Cost of Treatment: A Physician’s Perspective

Mark Pegram, MD, University of Miami: It is a pleasure to introduce Sylvia from NYU and is Chairman and Professor in the Department of Radiation Oncology at the NYU School of Medicine where she also directs the Clinical Research and Co-Leader of the Breast Cancer Research Program at the Cancer Institute there and we’re happy to have her give her thoughts on current costs of treatment and survivors’ experience.

Silvia C. Formenti, MD, New York University School of Medicine: Thank you; so I’ll—thank you very much. I will give a much more general introduction and I think Pat deserves the last word. So you know to talk about the cost of treatment is—in 20 minutes, in 15 minutes is quite a challenge, so I’ll try to give a little bit of my two cents about it. So I’ll try to tell you about the dollar costs of breast cancer in the United States and you know just stress again what we’ve got for the money, try to allude a little bit to the collateral damage, so and again I’ll go back to what is very close to my shop which is Radiotherapy for Breast Cancer and what it’s done. And then I’ll try to adventure a little bit on the—on the challenge of the global implications and what we can do right or wrong globally.

So approximately $16.5 billion is spent each year in the United States on breast cancer diagnosis and treatment. Then you have to add the lost productivity due to breast cancer for an additional $12.1 billion. And then approximately—it’s very difficult to measure exactly how much, but approximately $2.5 billion for breast cancer-specific peer-reviewed research and there are a lot of other initiatives that fund research, but the most documented ones is approximately that amount.

And the conclusion is that it is the most costly form of disease in the United States due to its high incidence. That’s the way industry is looking at it, but it’s also clearly due to the fact that we haven't cured it yet. So what does this amount of money every year really buy us?

So you know no question, you know mortality is going down; slow and gradually it’s going down and I just want to stress this is divided—the curves are reported by age groups. I just again want to stress what John had alluded before that this is going down, but it’s going down more in white women and not so much in black women. And then there is even an issue on different age groups whether it’s going down sufficiently, for instance in the older women.

And if we look at really just the way to like a rule of thumb to memorize what’s going on is that over the past 10 years we got a 1% decrease in breast cancer mortality. Already you have seen this slide and probably we can discuss what is really a third to half or whatever, but one half from screening and one half from treatment; so as—as John has alluded to this is a long way to go if we really want to eradicate the disease.

So if—even defining the cost standpoints which we spoke about money but you know it seems to me that there is a persistent loss of life to breast cancer and I know it’s obvious that it’s a cost—breast cancer mortality but just I want to stress that each of the single patient who dies of breast cancer has endured the cost of treatment and clearly without the advantage of surviving the disease. So that to me is the biggest cost. And then you know there are issues, you know whether doctors you know often make mistakes, so even things we have done that may have increased the incidence and I’ll talk for a minute about it.

There is a loss of the quality of life because of the disease and—and/or the treatment and of course you know there are costs in terms of other causes of mortality after breast cancer and then the gigantic iceberg over-diagnosis and over-treatment.

So this is you know a bunch of curves that are very suggestive for, you know, and misleading information, the medical community had adopted that in fact hormone replacement therapy was a good idea. And as you can see you know the—if you look at this is the pool data from 9 SEER Registry from nine different States in the United States, you can see from you know in terms of the change of a time when women less than 50 years of age, not much of a change, but a modification in terms of increase maybe eventually, a bit of increase after menopause when most likely women were using a hormone replacement therapy. And this is a provocative paper that alluded to the fact that in fact the—there is a correlation between fewer prescriptions for hormone replacement therapy after the evidence was presented that it was in fact detrimental and the decrease in ER positive tumors but not much of a difference in ER negative tumors.

So sometimes we can interfere with incidents because this was really a heterogenic increase of incidents by the prescription of hormone replacement therapy. We certainly have made a big difference in quality of life and I certainly do not underestimate this impact. You know this is—it was a very common outcome after surgery in the 70s and over the years has evolved in optimum medical result that is much more than just cosmetics. It’s integrity of body image and—and you know and much better outcome. And this was obtained with the inclusion of radiotherapy in breast preservation.

And once again it came with consequences and was—where I alluded before but you know interestingly enough the addition of breast—of radiotherapy to breast cancer treatment had also an impact on increasing survival of the women who were recipients of radiotherapy, so not only look at control; there was evidence of an increase in survival, but—from breast cancer. But when you look at known breast cancer death that was a big price; you practically lost that advantage because you had an increase in mortality. This is the percentage of women who are surviving and the ones who had radiotherapy were less likely to survive as a consequence of known breast cancer. So of course you know the price was an increase in cardiovascular mortality so of course a good idea to spare their heart and we’ve known this for—for many years and it became very evident in 2000.

But it became strikingly evident when Sarah Darby published the long-term review on 300,000 women from US SEER Registry—Registries where she compared the right—everybody got radiation; she compared the women who got the radiation to the right with women who got the radiation to the left breast. And it turns out when you radiate the left breast inevitably in the supine position in the sizable proportion of women you would include in the tangent fields of radiation part of their heart and this is a coronary artery that is very relevant with the profusion of the heart. And what she found was in fact a drastic increase in cardiac mortality. So if you were unlucky enough to have left breast cancer instead of right breast cancer you were more—much more likely that your counterpart with right breast cancer and received the same treatment, just because of the effect of radiation.

As John has pointed out, it took a long—many years and it stays as an increased risk for life. It doesn’t really go away. It took many years to learn about it and it’s a big concern. And to me very important as well is that you know they’ve noticed ipsilateral increased lung cancer death if—for both sides if you were to receive radiotherapy compared to women who did not get radiotherapy, so both very important points because part of the lung is in the field and it’s not just the part that is in the field but approximate part to the field that is really relevant because it’s exposed. So you know very stupid, very banal solution is to flip woman and try to see whether to adjust positionally you can avoid that. And it turns out that your Department of Defense funded us and others in this direction that you know you really can make a difference, so you can avoid and spare—just have the heart outside the field and avoid heart and lung much more swiftly in most patients. And it got even the attention of the New York Times, so it must be science you know of course.

So and here you can see that just—that the same woman when she’s supine she gets a little bit of heart and lung in the field. You put her prone you can avoid both of them. And you have no idea how difficult it is to convince the medical community that you can do it; you just have to turn the woman on the prone position.

But anyway in—in reality is that we have a progress. We have an increase in the—and this is the slide we all often show—it was shared by ASCO; they came to all physicians. I guess it’s a form of success of what we’ve done in breast cancer survival. So no question; more women—19% more are alive at 5 years compared to the 80s or you know the—the late 70s. So it’s definitely important for women who have breast cancer—no question in my mind, so I wouldn’t consider it a small effect. It is a sizable important effect, but really is achieved by treating everybody, so in order to get this you have to treat either adjuvantly, neo-adjuvantly, or occurrence and many of these women do not derive the benefit. So it’s been done. We got to this point where it—an indiscriminate use of treatment and a lot of costs.

So you know and this is particularly striking in my mind when you look at metastatic disease. So when the disease comes back and I really felt this was an important paper to focus on that just came out from Stockler and Tattersall where they try to—this is a group of physicians and epidemiologists and they’re trying to get in the shoes of the patient and trying to think what gets into the mind of a patient with metastatic disease and how as physicians we present options.

And in reality when we show curves whether it’s comparing a new treatment to a conventional treatment for metastatic disease, they’re all very similar to this—these curves, and these authors look at you know unfortunately it’s a very few if you think about how common metastatic diseases—27 trials they could find in the literature between 1999 and 2009 that were all randomized and were given at first line of metastatic disease and had at least 90 patients per arm and outcome survival data that they could measure. And they were able to show that incredible consistency within the trial, so you know you really can interpret these curves trying to give a much more precise sense of you know if I take the toxicity of this drug, so I get this cost, what is my likelihood of having an advantage?

And you know and somehow figure out how to—to present the mean value in [inaudible] scenario that would go from the worst scenario, it didn't really work for me, to being in the middle, lower typical, upper typical, so between a year and 3 years of advantage and the best case—and of course people that do extremely well and we’ll like to remember those and focus on those, but you know throughout this entire process, all these patients here have lost.

Every time we look at these curves we focus on the difference between the curves; we should rather focus on how fast these curves you know drop down and how much is a price of everybody being treated.

So in between you know almost concomitantly to this paper, there was a position paper from ASCO that is an extraordinary kind of powerhouse for oncology where you know they somehow stated a mission to bring you know the way we do oncology in the United States to low and middle income countries. And you know with the risk of harping again—harping again on the same concept, it seems to me that we should be very cautious before going global because you have seen the cost of what—what this country is spending in this moment and what we get for that money and just if we were to apply for instance the rate of mammograms, we do approximately 36,000,000 mammograms per year, and if we’re talking about $3 to $4 billion for a population the size of the United States. And it’s not just the—the cost itself and the strategic choice of proposing that but it’s also an issue that maybe breast cancer worldwide is very different from what we see in the United States.

And, you know this is a global kind of estimate of incidence versus mortality. And one very common way to report this as John has pointed out is really the ratio between mortality versus incidence where we do very well, right. So we have much more incidence and we do very well in terms of mortality compared to Tanzania for instance. But these are numbers—they’re absolute numbers per 100,000 women, age-grouped. So if you look at it in terms of the precise—with all the biases that Tanzania may be—they’re not reported and die of other causes, they have concomitant breast cancer so it extends to other causes, but all these biases. You know maybe the story is a little bit different because when you look at the incredible similarity of the mortality across the world you may ask the question maybe this ratio may not be the best way to look at the picture and maybe we have an effect of delusion about those trivial cancers that John alluded to that in—for instance has inflated our breast cancer problem with the screening of a lot of you know pre-neoplastic and pre-invasive, and now a lot of attention of dysplasia and so on and a lot of procedures.

So a concern about disporting it and last but not least I’m sure you all have—have seen this very interesting report from the experience in Norway where you know they had difference policies of screening with different frequencies of screening and they expect that eventually that if you screen less frequently women eventually—it will catch up in terms of detecting the incidence of tumors and in fact you know it didn't happen. And the least—less frequently screened sub-set maintained a difference in incidence suggesting that at least some of the breast cancer may regress. So that’s complicated the factor even further and of course we don’t know how much is the breast cancer regressing or the carrier being able to handle the breast cancer in a more efficient way and rejecting it.

So if we want to really transfer the little we know and what we have learned I think what is really important is really to look at even the incidence worldwide. And it turns out that the incidence, pre-menopausal is probably pretty much the same worldwide, but then you know in developing countries—for instance here it Thailand, it goes down after menopause which is not exactly the course that it takes in our country. So the—if you want to introduce mammography in those countries where you know we know in pre-menopausal women it doesn’t work that well because the breast is much more dense and more difficult to screen with conventional mammography, it will be even less effective because the problem is mostly in younger women and it peaks earlier.

A good example is Egypt where they have a pretty well-organized tumor registry so this concern of not reporting is somehow avoided and they’ve shown very nicely that in fact the incidence of the disease is earlier compared—this is the median versus the mean incidence, so the women tend to have breast cancer earlier compared to the United States.

So because of that you know you—if you were to talk like mammograms you like to screen many more to detect one cancer, so it would be even less efficient independently from the cost of mammography itself. So what is the cost of doing a diagnosis, even in the United States? So I think this is a very nice work in that the Journal of National Cancer Institute that was published a couple of years ago where you try to look from a 50 year-old American woman what it really does to undergo a benefit of screening. And please notice nobody ever talks to women in the process of consent about harms of screening. We always take for granted that it is only good news. But you know among—you know if you have five women in 1,000 that are not screened, among the women who are not screened you will have five out of 1,000 deaths over 10 years compared to four in a—in 1,000 deaths if you undergo annual screenings with mammography. But the price for that is a higher chance to having at least false positive mammogram that results in a biopsy and is you know calculated to be 50 to 100 more every 1,000 women screened, and unnecessary diagnosis and treatment probably 2 to 10 more over—you know that is over 1,000 screened. So there is a price and—and I think it’s really something to talk about whether this extra life saved is—is really worth it and—and you know of course any life is worth it but without discussing the price. And I think women should consent with the knowledge of this price.

So in my opinion at least at this point the rate of progress is much, much too slow. A large proportion of women diagnosed with breast cancer will not derive their own individual benefit from treatment either because they do not need it or because it does not work for them and may in fact bring them some damage. Understanding breast cancer in developing countries may provide better solution to reduce the human and financial cost of breast cancer in the United States. So I’ll stop here.