lecture-9原文

1、Listening: Lecture 9Lecture9 A new tool to find breast tumorsThere are two groups of women when it comes to screening mammographywomen in whom mammography works very well and has saved thousands of lives and women in whom it doesnt work well at all. Do you know which group youre in? If you dont, you

2、re not alone. Because the breast has become a very political organ. The truth has become lost in all the rhetoric coming from the press, politicians, radiologists and medical imaging companies. I will do my best this morning to tell you what I think is the truth. But first, my disclosures: I am not

3、a breast cancer survivor. Im not a radiologist. I dont have any patents, and Ive never received any money from a medical imaging company, and I am not seeking your vote. (Laughter) What I am is a doctor of internal medicine who became passionately interested in this topic about 10 years ago when a p

4、atient asked me a question. She came to see me after discovering a breast lump. Her sister had been diagnosed with breast cancer in her 40s. She and I were both very pregnant at that time, and my heart just ached for her, imagining how afraid she must be. Fortunately, her lump proved to be benign. B

5、ut she asked me a question: How confident was I that I would find a tumor early on her mammogram if she developed one? So I studied her mammogram, and I reviewed the radiology literature, and I was shocked to discover that, in her case, our chances of finding a tumor early on the mammogram were less

6、 than the toss of a coin. You may recall a year ago when a firestorm erupted after the United States Preventive Services Task Force reviewed the worlds mammography screening literature and issued a guideline recommending against screening mammograms in women in their 40s. Now everybody rushed to cri

7、ticize the Task Force, even though most of them werent in anyway familiar with the mammography studies. It took the Senate just 17 days to ban the use of the guidelines in determining insurance coverage. Radiologists were outraged by the guidelines. The pre-eminent mammographer in the United States

8、issued the following quote to The Washington Post. The radiologists were, in turn, criticized for protecting their own financial self-interest. But in my view, the radiologists are heroes. Theres a shortage of radiologists qualified to read mammograms, and thats because mammograms are one of the mos

9、t complex of all radiology studies to interpret, and because radiologists are sued more often over missed breast cancer than any other cause. But that very fact is telling.Where there is this much legal smoke, there is likely to be some fire. The factor most responsible for that fire is breast densi

10、ty. Breast density refers to the relative amount of fatpictured here in yellowversus connective and epithelial tissuespictured in pink. And that proportion is primarily genetically determined. Two-thirds of women in their 40s have dense breast tissue, which is why mammography doesnt work as well in

11、them. And although breast density generally declines with age, up to a third of women retain dense breast tissue for years after menopause. So how do you know if your breasts are dense? Well, you need to read the details of your mammography report. Radiologists classify breast density into four cate

12、gories based on the appearance of the tissue on a mammogram. If the breast is less than 25 percent dense, thats called fatty-replaced. The next category is scattered fibroglandular densities, followed by heterogeneously dense and extremely dense. And breasts that fall into these two categories are c

13、onsidered dense. The problem with breast density is that its truly the wolf in sheeps clothing. Both tumors and dense breast tissue appear white on a mammogram, and the X-ray often cant distinguish between the two. So its easy to see this tumor in the upper part of this fatty breast. But imagine how

14、 difficult it would be to find that tumor in this dense breast. Thats why mammograms find over 80 percent of tumors in fatty breasts, but as few as 40 percent in extremely dense breasts. Now its bad enough that breast density makes it hard to find a cancer, but it turns out that its also a powerful

15、predictor of your risk for breast cancer. Its a stronger risk factor than having a mother or a sister with breast cancer. At the time my patient posed this question to me, breast density was an obscure topic in the radiology literature, and very few women having mammograms, or the physicians orderin

16、g them, knew about this. But what else could I offer her? Mammograms have been around since the 1960s, and its changed very little. Thereve been surprisingly few innovations, until digital mammography was approved in 2000. Digital mammography is still an X-ray of the breast, but the images can be st

17、ored and manipulated digitally, just like we can with a digital camera. The U.S. has invested four billion dollars converting to digital mammography equipment, and what have we gained from that investment? In a study funded by over 25 million taxpayer dollars, digital mammography was found to be no

18、better over all than traditional mammography, and in fact, it was worse in older women. But it was better in one group, and that was women under 50 who were pre-menopausal and had dense breasts, and in those women, digital mammography found twice as many cancers, but it still only found 60 percent.

19、So digital mammography has been a giant leap forward for manufacturers of digital mammography equipment, but its been a very small step forward for womankind. What about ultrasound? Ultrasound generates more biopsies that are unnecessary relative to other technologies, so its not widely used. And MR

20、I is exquisitely sensitive for finding tumors, but its also very expensive. If we think about disruptive technology, we see an almost ubiquitous pattern of the technology getting smaller and less expensive. Think about iPods compared to stereos. But its the exact opposite in health care. The machine

21、s get ever bigger and ever more expensive. Screening the average young woman with an MRI is kind of like driving to the grocery store in a Hummer. Its just way too much equipment. One MRI scan costs 10 times what a digital mammogram costs. And sooner or later, were going to have to accept the fact t

22、hat health care innovation cant always come at a much higher price. Malcolm Gladwell wrote an article in the New Yorker on innovation, and he made the case that scientific discoveries are rarely the product of one individuals genius. Rather, big ideas canbe orchestrated, if you can simply gather peo

23、ple with different perspectives in a room and get them to talk about things that they dont ordinarily talk about. Its like the essence of TED. He quotes one innovator who says, “The only time a physician and a physicist get together is when the physicist gets sick.” (Laughter) This makes no sense, b

24、ecause physicians have all kinds of problems that they dont realize have solutions. And physicists have all kinds of solutions for things that they dont realize are problems. Now, take a look at this cartoon that accompanied Gladwells article, and tell me if you see something disturbing about this d

25、epiction of innovative thinkers. (Laughter) So if you will allow me a little creative license, I will tell you the story of the serendipitous collision of my patients problem with a physicists solution. Shortly after her visit, I was introduced to a nuclear physicist at Mayo named Michael OConner, w

26、ho was a specialist in cardiac imaging, something I had nothing to do with. And he happened to tell me about a conference hed just returned from in Israel, where they were talking about a new type of gamma detector. Now gamma imaging has been around for a long time to image the heart, and it had eve

27、n been tried to image the breast. But the problem was that the gamma detectors were these huge, bulky tubes, and they were filled with these scintillating crystals, and you just couldnt get them close enough around the breast to find small tumors. But the potential advantage was that gamma rays, unl

28、ike X-rays, are not influenced by breast density. But this technology could not find tumors when theyre small, and finding a small tumor is critical for survival. If you can find a tumor when its less than a centimeter, survival exceeds 90 percent, but drops off rapidly as tumor size increases. But

29、Michael told me about a new type of gamma detector that hed seen, and this is it. Its made not of a bulky tube, but of a thin layer of a semiconductor material that serves as the gamma detector. And I started talking to him about this problem with breast density, and we realized that we might be abl

30、e to get this detector close enough around the breast to actually find small tumors. So after putting together a grid of these cubes with tape(Laughter)Michael hacked off the X-ray plate of a mammography machine that was about to be thrown out, and we attached the new detector, and we decided to cal

31、l this machine Molecular Breast Imaging, or MBI. This is an image from our first patient. And you can see, using the old gamma technology, that it just looked like noise. But using our new detector, we could begin to see the outline of a tumor. So here we were, a nuclear physicist, an internist, soo

32、n joined by Carrie Hruska, a biomedical engineer, and two radiologists, and we were trying to take on the entrenched world of mammography with a machine that was held together by duct tape. To say that we faced high doses of skepticism in those early years is just a huge understatement, but we were

33、so convinced that we might be able to make this work that we chipped away with incremental modifications to this system. This is our current detector. And you can see that it looks a lot different. The duct tape is gone, and we added a second detector on top of the breast, which has further improved

34、 our tumor detection. So how does this work? The patient receives an injection of a radio tracer thats taken up by rapidly proliferating tumor cells, but not by normal cells, and this is the key difference from mammography. Mammography relies on differences in the appearance of the tumor from the ba

35、ckground tissue, and weve seen that those differences can be obscured in a dense breast. But MBI exploits the different molecular behavior of tumors, and therefore, its impervious to breast density. After the injection, the patients breast is placed between the detectors. And if youve ever 44 had a

36、mammogramif youre old enough to have had a mammogramyou know what comes next: pain. You may be surprised to know that mammography is the only radiologic study thats regulated by federal law, and the law requires that the equivalent of a 40-pound car battery come down on your breast during this study

37、. But with MBI, we use just light, pain-free compression. (Applause) And the detector then transmits the image to the computer. So heres an example. You can see, on the right, a mammogram showing a faint tumor, the edges of which are blurred by the dense tissue. But the MBI image shows that tumor mu

38、ch more clearly, as well as a second tumor, which profoundly influence that patients surgical options. In this example, although the mammogram found one tumor, we were able to demonstrate three discrete tumorsone is small as three millimeters. Our big break came in 2004. After we had demonstrated th

39、at we could find small tumors, we used these images to submit a grant to the Susan G. Komen Foundation. And we were elated when they took a chance on a team of completely unknown investigators and funded us to study 1,000 women with dense breasts, comparing a screening mammogram to an MBI. Of the tu

40、mors that we found, mammography found only 25 percent of those tumors. MBI found 83 percent. Heres an example from that screening study. The digital mammogram was read as normal and shows lots of dense tissue, but the MBI shows an area of intense uptake, which correlated with a two-centimeter tumor.

41、 In this case, a one-centimeter tumor. And in this case, a 45-year-old medical secretary at Mayo, who had lost her mother to breast cancer when she was very young, wanted to enroll in our study. And her mammogram showed an area of very dense tissue, but her MBI showed an area of worrisome uptake, wh

42、ich we can also see on a color image. And this corresponded to a tumor the size of a golf ball. But fortunately it was removed before it had spread to her lymph nodes. So now that we knew that this technology could find three times more tumors in a dense breast, we had to solve one very important pr

43、oblem. We had to figure out how to lower the radiation dose, and we have spent the last three years making modifications to every aspect of the imaging system to allow this. And Im very happy to report that were now using a dose of radiation that is equivalent to the effective dose from one digital

44、mammogram. And at this low dose, were continuing this screening study, and this image from three weeks ago in a 67-year-old woman shows a normal digital mammogram, but an MBI image showing an uptake that proved to be a large cancer. So this is not just young women that its benefiting. Its also older

45、 women with dense tissue. And were now routinely using one-fifth the radiation dose thats used in any other type of gamma technology. MBI generates four images per breast. MRI generates over a thousand. It takes a radiologist years of specialty training to become expert in differentiating the normal

46、 anatomic detail from the worrisome finding. But I suspect even the non-radiologists in the room can find the tumor on the MBI image. But this is why MBI is so potentially disruptiveits as accurate as MRI, its far less complex to interpret, and its a fraction of the cost. But you can understand why

47、there may be forces in the breast-imaging world who prefer the status quo. After achieving what we felt were remarkable results, our manuscript was rejected by four journals. After the fourth rejection, we requested reconsideration of the manuscript, because we strongly suspected that one of the rev

48、iewers who had rejected it had a financial conflict of interest in a competing technology. Our manuscript was then accepted and will be published later this month in the journal Radiology. (Applause) We still need to complete the screening study using the low dose, and then our findings will need to

49、 be replicated at other institutions, and this could 45 take five or more years. If this technology is widely adopted, I will not benefit financially in any way, and that is very important to me, because it allows me to continue to tell you the truth. But I recognize(Applause)I recognize that the ad

50、option of this technology will depend as much on economic and political forces as it will on the soundness of the science. The MBI unit has now been FDA approved, but its not yet widely available. So until something is available for women with dense breasts, there are things that you should know to

51、protect yourself. First, know your density. Ninety percent of women dont, and 95 percent of women dont know that it increases your breast cancer risk. The State of Connecticut became the first and only state to mandate that women receive notification of their breast density after a mammogram. I was

52、at a conference of 60,000 people in breast-imaging last week in Chicago, and I was stunned that there was a heated debate as to whether we should be telling women what their breast density is. Of course we should. And if you dont know, please ask your doctor or read the details of your mammography report. Seco