Saving Women's Lives Strategies for Improving Breast Cancer Detection and Diagnosis: A Breast Cancer Research Foundation and Institute of Medicine Symposium (2005) / Chapter Skim
Currently Skimming:
Plenary Session
Plenary Session
Pages 6-67
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 6... ...
and National Research Council's (NRC's) National Cancer Policy Board on breast cancer research for several years, and in particular has been an important supporter of this project and co-sponsor of this symposium.
|
From page 7... ...
In 1993, I led a delegation of Estee Lauder executives and editors from Self magazine to Washington, D.C., and we raised a window shade on which had been pinned 250,000 names. Through coverage of this event in the national press and television and our visit to Hillary Clinton at the White House, we drew attention to the fact that the federal government needed desperately to give more funds for breast cancer research.
|
From page 8... ...
The committee focused on identifying which approaches are likely to save the most lives in the near term. This includes technology in the broadest sense -- from specific tools such as digital mammography, MRI, biomarkers, and proteomics to how these tools and strategies can be most efficiently deployed in clinical practice.
|
From page 9... ...
In the afternoon, there will be two concurrent group discussions, ending with a plenary wrap-up discussion. The Pros and Cons of Screening Mammography: What Women Need to Know -- An Overview of the Report's Findings on Mammography Laura Esserman, M.D., M.B.A., Director, Carol Franc Buck Breast Care Center and Professor of Surgery and Radiology University of California, San Francisco The first thing that women need to know is that mammography is early detection, not prevention.
|
From page 10... ...
There really is no other technology that has been shown to systematically find tumors at an earlier stage, and 12 countries have implemented systematic screening programs. Participants in the global mammography summit in June 2002 reviewed the available evidence and unanimously decided that there was no reason to change screening programs.
|
From page 11... ...
MRI certainly is useful when we know someone is at extremely high risk for developing breast cancer. For women with genetic susceptibility, some of whom are known to have an 80 percent lifetime risk of developing breast cancer, MRI, even though expensive, has been shown to be much more sensitive than screenfilm mammography, particularly because those being screened are young women with dense breast tissue in whom underlying breast tumors are more likely to occur (Kriege et al., 2004)
|
From page 12... ...
perhaps than in countries where they have more focused screening programs. The organization of care clearly affects the quality of screening.
|
From page 13... ...
Where there are focused, organized screening programs, the fraction of positive operative breast biopsies can be 80 to 90 percent (UK) or 85 to 95 percent (Sweden)
|
From page 14... ...
. For example, new data from the Women's Health Initiative, shown in Figure 2.4, indicate that some populations, such as African American women, have different types of breast cancer, so that, although the frequency may be lower, more aggressive, poorly differentiated plus estrogen receptor negative tumors are much more frequent.
|
From page 15... ...
Significantly increased FIGURE 2.4 African American women have significantly more aggressive, poorly differentiated, estrogen receptor (ER) negative breast cancer.
|
From page 16... ...
FIGURE 2.6 Poverty is the greatest barrier to mammography screening.
|
From page 17... ...
Mammography is most beneficial in women ages 50 -70 Most likely to have the cancers with growth rates where screening is most beneficial Breast cancer risk is not Risk of breast cancer increases with age, well understood and that but frequency of mammography tapers . 13.5 million women over 65 screened affects breast cancer care 7.2 million women over 65 not screened 2001 Census Bureau/ACS data Late age: · Other competing risks of death make breast cancer less important Cost effectiveness 3 -5x higher in women 50 -70 than 40-50 Younger women · Risk of having cancer lower · Sensitivity of mammography lower · Recall and biopsy rate higher · Higher risk of tumors with higher growth fraction (node + at diagnosis)
|
From page 18... ...
But there is enormous variation in the odds of having cancer in this category -- from 3 to 75 percent. It might be an in situ pre-cancer, or it might be an invasive cancer, and it might often lead to biopsy and contribute to the false positive rate and create quite a bit of alarm.
|
From page 19... ...
New technologies such as digital mammography create opportunities for change such as the addition of technologies like computerized decision aids which can reduce the difference between the average mammographer and the expert mammographer. We recommend considering adoption in the United States of elements of successful breast cancer screening programs from other countries, including centralized expert interpretation, regionalization of programs, outcomes analysis, and benchmarking.
|
From page 20... ...
We have recommended that research funders help develop tools that facilitate communication regarding breast cancer risk to the public and health care providers, so that we really understand the various risks and benefits, including the risks associated with emerging biomarkers. That means finding ways to teach women about their risks and the benefits of interventions.
|
From page 21... ...
The countermeasures include producing more radiologists, improving their productivity (work harder, physician extenders, computer assisted diagnosis) , initiating tort reform, and adjusting the payment schedule.
|
From page 22... ...
We can no longer respond as a normal market economy; we are limited by that artificial cap. Box 2.2 shows the number of residency positions offered by the radiology matching program, the precipitous decline in the late 1990s, and the gradual slow increase thereafter.
|
From page 23... ...
And finally, board certification is yet another hurdle that is a particular problem for mammography because of Mammography Quality Standards Act (MQSA) regulations.
|
From page 24... ...
For our carrier, the professional component of the fee for screening mammography is $40 and for diagnostic mammography $49. Our mammography group would say that the difference in effort between these two is three to one, not five to four.
|
From page 25... ...
We could use physician extenders. We could take advantage of technology, and we have computer assisted diagnosis systems that might be employed.
|
From page 26... ...
Mammography Services: Implications for Accuracy and Encouragement of Screening. Better Quality Through Better Organized Mammography Robert Smith, Ph.D., Director of Cancer Screening, American Cancer Society What might we achieve, or not achieve, through better organized screening?
|
From page 27... ...
A successful screening program requires participation by a target population and health care providers and adherence to recommendations, especially the screening interval. Screening intervals are established based upon estimates of a detectable preclinical phase, the sojourn time.
|
From page 28... ...
. Thirty percent of breast cancers were not found on mammography, and these were also larger than those found on women who followed screening recommendations.
|
From page 29... ...
SOURCE: Michaelson et al., 2002. As noted earlier, opportunistic, that is, encounter -- not population -- based screening is one of the reasons for poor adherence to mammography screening recommendations.
|
From page 30... ...
A meta-analysis of 108 studies of strategies to increase rates of adult immunization and cancer screening through interventions including reminders, organizational change, feedback, education, financial incentives, legislative change, mass media, and even separate preventive care clinics found that organizational change was most effective in improving rates of preventive care. Among such effective changes were use of separate clinics devoted to prevention, use of a
|
From page 31... ...
In addition, one reasonable strategy for breast cancer, since I think that a centralized system is relatively hopeless at the moment, might be simply to encourage radiology departments to manage the callrecall system. Ultimately, a more organized approach to breast cancer screening would monitor population-based access.
|
From page 32... ...
estimated that, assuming 4,500 exams per 10,000 women per year, there should be approximately 2.2 mammography machines for every 10,000 women in the population if around 90 percent compliance with screening recommendations is the objective. Only five states have a ratio of 2.2 machines per 10,000 women, and 11 states have a ratio of two per 10,000 women, so it seems that the majority of states do not have the capacity to deliver recommended services at the 90 percent adherence rate.
|
From page 33... ...
The positive predictive value, that is, the proportion of women with an abnormal mammogram that actually have breast cancer, is lower in younger women, but these numbers improve as women get older. Across the board, the median tumor size is quite small, and the percent of node-negative tumors approaches 3 out of 4.
|
From page 34... ...
New York State has taken an oversight responsibility for the 292 facilities that participate in their state's Breast and Cervical Cancer Screening Program funded through the CDC National Breast and Cervical Cancer Early Detection Program (Hutton et al., 2004)
|
From page 35... ...
After corrective action, the number of BI-RADS® 4 readings dropped to 4.3 percent; additional imaging to reconcile abnormalities more than doubled; biopsy rates in women after abnormal mammograms declined substantially, and the positive predictive value for biopsies increased. This sensible surveillance strategy can improve the quality of breast imaging in ways that are difficult for voluntary programs or the Mammography Quality Standards Act to achieve, and it also can detect fraud and dangerously low quality.
|
From page 36... ...
First of all, resource issues may take precedence over evidence, both nationally and locally. For example, screening programs in Europe may have elements, such as the recommended 3-year screening interval in the United Kingdom, that are due to resource limitations and are not in keeping with available evidence.
|
From page 37... ...
0.0 0 5 10 15 20 25 30 35 Time(Year) FIGURE 2.10 Dramatic improvements in survival in breast cancer in populations with high-quality organized screening: cumulative survival of breast cancer patients age 40-69 in Dalarna, Sweden.
|
From page 38... ...
I am not optimistic about that approach, because the current system is inefficient. Do you see as a possibility having freestanding organized screening programs as a way to give some status to radiologists who do mammography, to increase the finances, to increase the efficiency?
|
From page 39... ...
Prior to the program, 90 percent of all breast cancer patients were cared for by general practitioners. Within 7 years of instituting the screening program, 95 percent of all women were treated in organized breast centers.
|
From page 40... ...
In terms of the Gail model, no, the Gail risk model is not out. At a risk models meeting here a few weeks ago, integration of the approach to prevention and screening with understanding underlying risk was discussed as a way to tailor screening strategies.
|
From page 41... ...
We know that the sojourn time for women ages 50 and above is quite long; 3 years is a common estimate. So a 2-year screening interval is something to consider as a way of increasing capacity and access.
|
From page 42... ...
The task is to pick up malignancy. False positives are the currency that you pay to detect subtle malignancy; as you increase false positives, your false negatives decrease.
|
From page 43... ...
In my presentation today, I will discuss the science of risk stratification, breast cancer risk in context, and breast cancer risk perception. I will spend most of my time on the first topic.
|
From page 44... ...
; increased breast density; and strong family history. Box 2.5 lists many of the risk factors that BOX 2.5 Moderate Risk Factors for Breast Cancer Moderate Risk Factors for Breast Cancer with Relative Risks 1.0-3.0 Mother or sister with breast cancer Increased bone density Older age at first birth Older age at menopause Younger age at mearche Benign breast biopsy Alcohol consumption HRT/Contraceptive pills
|
From page 45... ...
. However, the Gail model did not work as well for individual women, and that is what is needed for risk stratification.
|
From page 46... ...
If the figure displayed absolute numbers instead of percentages, the group that did not develop breast cancer would swallow up the group that did. 0.25 0.20 ofsample0.15 0.10 Did not develop breast cancer Proportion Developed breast cancer 0.05 0.00 0 0.025 0.05 0.075 0.1 Estimated 5-year risk FIGURE 2.11 Discrimination of the Gail model.
|
From page 47... ...
In the Gail model, the relative risks were small. Except for age, no factors with very large risks were included.
|
From page 48... ...
It appears the risks that work for breast cancer risk stratification are ones with very large relative risks, or perhaps a combination of factors that add up to a very large relative risk. In summary, risk stratification may be difficult because most risks for breast cancer are small and because many of these risk factors are spread out over the entire population.
|
From page 49... ...
When I was at the University of North Carolina, and it got to be known that I was involved in breast cancer screening and prevention, several college students in their early twenties would come to my practice worried about breast cancer. For the vast majority, I could not find anything that would suggest they were at increased risk.
|
From page 50... ...
In conclusion, the committee made two major recommendations about breast cancer risk. The first was to develop individually tailored risk prediction tools to identify women who would benefit from individualized approaches to breast cancer detection.
|
From page 51... ...
Of course, now we realize that things are a lot more complex, that while there are perhaps only 30,000 genes, those 30,000 genes produce upwards of a million different proteins. I believe we should now develop strategies that allow us comprehensively to identify and characterize all the proteins being produced by breast cancer cells as a more direct way to find those particular proteins that could be promising diagnostic or therapeutic targets.
|
From page 52... ...
An initiative to characterize all proteins expressed on the surface of breast cancer cells would have tremendous benefit through identifying those subsets that are important for diagnosis, molecular imaging, or therapy. There are two or three groups at the present time that are investigating proteins that are secreted by tumor cells.
|
From page 53... ...
that allows profiling thousands of very low abundance proteins and identifying those of high value that may represent markers for different disease states, including breast cancer. The Human Proteome Initiative, with the support of NIH as well as numerous industry groups, is an effort to utilize all of the proteomics technologies to comprehensively quantify and characterize all the proteins in human serum.
|
From page 54... ...
We can display all the proteins from cancer cell lines on membranes, or blots, and, using sera from different subjects, explore which of the proteins from a particular cancer are recognized by the immune system, that is, act as antigens and generate antibodies. In one of our studies of breast cancer proteins published three years ago, a particular group of three related proteins, called RS/DJ-1, from a breast cancer cell line, was recognized strongly by sera from four breast cancer patients but not by sera from healthy controls (Le Naour et al., 2001)
|
From page 55... ...
Some patients had both antigen and antibody, some patients had only antibody, and others had only antigen detectable, and counting those that had either an antigen or an antibody, roughly 50 percent of new breast cancer patients had evidence of this particular molecular marker. We are very early on in this process of discovering and then validating markers.
|
From page 56... ...
Sci., Chief Medical Officer and Director, Office of Clinical Standards and Quality, Centers for Medicare and Medicaid Services I am going to give you a framework for thinking about Medicare reimbursement policy for new technologies, focusing on some of the complexity that may not be well known, on some very fundamental statutory and regulatory barriers, and on the legal authority the program has to pay for screening and early detection technology. Medicare reimbursement falls into five components listed in Box 2.6, each about as complex as the whole.
|
From page 57... ...
That is why Medicare can pay for screening mammograms, but it is also why, as I noted earlier, other technologies besides screening mammography for early detection of breast cancer could not be covered without a statutory or regulatory change at the FDA. The actual language from Medicare law, section 1861(jj)
|
From page 58... ...
There is nothing, then, in the Medicare statute or regulations that would prevent inclusion of a much broader range of imaging technologies under the current statutory authority for paying for screening mammography if the FDA changed the definition of a screening mammogram as embedded in FDA regulations defining a radiologic procedure. Otherwise, it would probably require a statutory change to have any new breast cancer screening techniques paid for beyond the standard mammogram.
|
From page 59... ...
It involves a formally defined series of steps for submitting a request for coverage, so that an evidence review can be referred to an outside advisory committee or a formal technology assessment carried out. In reasonable and necessary decisions for diagnostic tests (like diagnostic mammography, for example)
|
From page 60... ...
It is covered for diagnosis not for screening, consistent with the usual rules on benefit categories I discussed earlier, but it is covered as an adjunct to standard staging in loco-regional or distant recurrence and monitoring for response to therapy. It is not covered for evaluating abnormal mammograms or palpable breast masses or for evaluation of axillary lymph nodes to decide on lymph node dissection.
|
From page 61... ...
There are many other unmet needs in society for health care services that should be balanced against additional spending for improvements in breast cancer technology or increases in payment to improve the quality of mammography.
|
From page 62... ...
SMITH: Dr. Fletcher, I thought you addressed the issue of risk stratification very nicely in terms of the Gail model in context and its application to identify a population for study.
|
From page 63... ...
DR. PETITTI, Kaiser Permanente: The promise of the ultra-low breast cancer risk group is demonstrated by the study of Cummings and colleagues showing that at some age there is a serum marker (serum estradiol level)
|
From page 64... ...
There are analogies in other fields of cancer screening; we are now finding that a 55-year-old woman who is human papilloma virus negative might not need a Pap smear every year, and there are analogies from the cardiovascular field, where someone who has a low density lipoprotein of 80 and a high density lipoprotein of 100 probably would not be a candidate for a screening test for early cardiovascular disease. So I think the ultra-low risk group is as important as the high risk group.
|
From page 65... ...
Here we thought women my age were supposed to be on longterm hormone replacement therapy to prevent several important chronic diseases, and all of a sudden not only the WHI but the Heart and Estrogen/Progestin Replacement Study and the Million Women Study are giving the lie to that conclusion. I was on the Board of Scientific Advisors at NCI, and there was concern about the high cost of the WHI.
|
From page 66... ...
We have examples in this report of recommendations that I think should be publicized and acted on. One of them is the notion that breast cancer screening, when applied in other countries in an organized fashion, has clearly been shown to reduce mortality.
|
From page 67... ...
PLENARY SESSION 67 DR. HANASH: The research community is vested in this, so it has to come from a third party, as opposed to we researchers trying to make a plea with the regulatory agency.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.