Mammogram for women over 40: Debate continues

[News]

A report this Wednesday showed that routine screenings for breast cancer called mammograms cut the breast cancer death rate by 26 percent for women in their 40s. The results have been received in a mixed way by experts.

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Dr. Peter C. Gotzsche of the Nordic Cochrane Center in Copenhagen, a nonprofit group that reviews health care research, has said in response to the just released study out of Sweden is that the investigators counted the number of women who received a diagnosis of breast cancer and also died of it. They did not compare the broader breast cancer death rates in the counties.

He said it is an important distinction because screening finds many cancers that do not need to be treated or found early. With more harmless cancers being found in the screened group, it will look like the chance of surviving breast cancer is greater in that group. “The analysis is flawed,” he said.

And Donald Berry, a statistician at MD Anderson Cancer Center, responded that the overdiagnosis problem was a serious one. "We are finding cancers that would never be found if we didn't look," he was quoted for the media. "Small wonder people think screening is great - some of the cancers it finds were not lethal in the first place."

It seems like the new Swedish study (not a randomized trial) would be far from convincing and probably wouldn't meet the USPSTF test for high-grade evidence. The authors made no adjustment for any risk factors.

The absolute risk revealed was quite small, about two-tenths of one percent. There were a total of 1,824 breast cancer deaths in the entire cohort, or roughly one of every 550 women. According to the authors of the study, 1,250 women in their 40's would have to be routinely given mammograms to prevent one breast cancer death.

As a result, a much larger proportion of those women would get false cancer signals, leading to unnecessary biopsies and other treatments. It was even suggested by the American Society of Clinical Oncology (ASCO) that women under 50 discuss with their doctors their own situation and the risks and benefits before going forward with routine mammograms.

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In a book written by Dr. H. Gilbert - Should I Be Tested for Cancer? - professor at the Dartmouth Medical School and co-director of the V.A. Outcomes Group in the Department of Veterans Affairs in White River Junction, Vt., admits that many doctors understand that early detection is a double-edged sword.

In fact, most learn about these problems in medical school. But once they are out of school all the forces are lined up to encourage them to test: whether it is making screening a measure of health-care quality (where the doctor who screens 100 percent is best), fear of legal liability from failure to diagnose (ever heard of a doctor sued for diagnosing cancer unnecessarily?) or financial pressure (it's quicker to order a test than to talk about why it might not be in your best interest).

For some common cancers, it is not clear that early detection and treatment actually prolong patients' lives. Early detection may just mean patients spend a longer time knowing they have cancer, and yet die at the same time they would have died anyway if the tumor had been diagnosed later. A decision to forgo cancer screening can be a reasonable option (Arch Intern Med. 2008;168(21):2300, 2302-2303, 2311-2316).

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Effectiveness of population-based service screening with mammography for ages 40 to 49 years

Authors

Barbro Numan Hellquist, Stephen W. Duffy, Shahin Abdsaleh, Lena Björneld, Pál Bordás, László Tabár, Bedrich Viták, Sophia Zackrisson, Lennarth Nyström, Håkan Jonsson

Abstract

BACKGROUND:

The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted.

METHODS:

Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow‐up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated.

RESULTS:

There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person‐years) and 1238 breast cancer deaths in the control group (8.8 million person‐years). The average follow‐up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% CI, 0.66‐0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.62‐0.80).

CONCLUSIONS:

In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality.

journal Cancer 2010 10.1002/cncr.25650

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Effect of Screening Mammography on Breast-Cancer Mortality in Norway

Mette Kalager, M.D., Marvin Zelen, Ph.D., Frøydis Langmark, M.D., and Hans-Olov Adami, M.D., Ph.D.

N Engl J Med 2010; 363:1203-1210September 23, 2010

Background

A challenge in quantifying the effect of screening mammography on breast-cancer mortality is to provide valid comparison groups. The use of historical control subjects does not take into account chronologic trends associated with advances in breast-cancer awareness and treatment.

Methods

The Norwegian breast-cancer screening program was started in 1996 and expanded geographically during the subsequent 9 years. Women between the ages of 50 and 69 years were offered screening mammography every 2 years. We compared the incidence-based rates of death from breast cancer in four groups: two groups of women who from 1996 through 2005 were living in counties with screening (screening group) or without screening (nonscreening group); and two historical-comparison groups that from 1986 through 1995 mirrored the current groups.

Results

We analyzed data from 40,075 women with breast cancer. The rate of death was reduced by 7.2 deaths per 100,000 person-years in the screening group as compared with the historical screening group (rate ratio, 0.72; 95% confidence interval [CI], 0.63 to 0.81) and by 4.8 deaths per 100,000 person-years in the nonscreening group as compared with the historical nonscreening group (rate ratio, 0.82; 95% CI, 0.71 to 0.93; P<0.001 for both comparisons), for a relative reduction in mortality of 10% in the screening group (P=0.13). Thus, the difference in the reduction in mortality between the current and historical groups that could be attributed to screening alone was 2.4 deaths per 100,000 person-years, or a third of the total reduction of 7.2 deaths.

Conclusions

The availability of screening mammography was associated with a reduction in the rate of death from breast cancer, but the screening itself accounted for only about a third of the total reduction. (Funded by the Cancer Registry of Norway and the Research Council of Norway.)

Source Information

From the Cancer Registry of Norway, Oslo (M.K., F.L., H.-O.A.); the Departments of Epidemiology (M.K., H.-O.A.) and Biostatistics (M.Z.), Harvard School of Public Health; and the Dana–Farber Cancer Institute and Harvard Medical School (M.Z., H.-O.A.) — all in Boston; and the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (H.-O.A.).

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An email from Dr. Russel Harris, Professor and Director of the Health Care & Prevention Concentration of the University of North Carolina School of Public Health, and former US Preventive Services Task Force member, and a recognized thought leader on issues of prevention and especially of screening tests, to Gary Schwitzer of the HealthNewsReview, giving analysis of the study. Read this carefully. You'll learn a great deal from his analysis.

"First, the authors say that their primary purpose is showing that there is a reduction in breast cancer mortality due to screening for women ages 40-49. It is worthwhile to point out that the US Preventive Services Task Force (USPSTF) agrees that there is a reduction in mortality in this group. Recall that the systematic review by Nelson et al found a relative risk reduction of 16% for this group, with a number needed to screen (NNS) for 10 years (with NNS you always have to give a length of time for the intervention) of about 2,000. The Swedish study found a relative risk reduction of 26%, with a NNS of 1252. The key issue is not whether there is a benefit, but rather how large the benefit is. In addition, this study says nothing about the harms of screening, while the USPSTF spent much time and energy trying to get a handle on the magnitude of the harms. The decision about screening (whether a policy decision or an individual patient decision) should hinge on the balance between the magnitude of benefits and the magnitude of the harms. So, we can discuss the difference in magnitude of benefit between this study and the USPSTF, but this study won't help us at all with the issue of the magnitude of the harms (including the experience of women with false positive results and the effects of overdiagnosis).

Now, to look at the Swedish study, it is also worthwhile to note that these investigators have an obvious point of view from the start. Their previous papers (especially Tabar and Duffy) have all come to the same conclusion - that screening is a good idea. The Swedish data, and the Norwegian data, are rich datasets and should be explored. However, in both cases it might make more sense for the investigators exploring these data to be clearly disinterested investigators who are not out to prove something. This becomes even more important as we get into the analysis required from such a dataset.

The research design of the Swedish study is a non-randomized trial, with primarily ecologic data (i.e., the data comes from large national databases of breast cancer diagnoses and deaths). When contrasting breast cancer mortality in large groups, two critical issues are (1) making sure the groups are comparable in all factors that might determine the outcome (breast cancer mortality). You want the groups, as much as possible, to differ only in that one group receives screening while the other does not. The other critical issue (#2) is that we could outcomes (breast cancer deaths) equally in both groups. If we count deaths unequally, we bias the results either in favor of or against screening.

In terms of the comparability of the groups, there are several problems:

• The areas that screened starting at 40 are better off than counties that started at 50, meaning that there are likely many other factors (such as treatment) that also are different in these groups. In terms of treatment, for example, the study period (1986-2005) witnessed an impressive improvement in breast cancer treatment. If these improvements in treatment occurred more in the study than the control areas, this could easily explain all of the difference between USPSTF and this study's estimates of the relative risk reduction for women 40-49.

• Some areas switched approaches during the study period - sometimes starting at 40 and sometimes at 50 (and one even at 45). This required statistical "adjustments". The best way to do these adjustments are not clear, and some might do them one way while others might do them another. The Norwegian study tried to take treatment into account - imperfectly, I am sure, but they probably got it at least partly right. The problem of how best to do these adjustments is a special problem for investigators who begin with a point of view. It would be very easy to adjust in a way favorable to their point of view and then justify themselves later.

In terms of which breast cancer deaths to count, this also is probematic:

• They (correctly) focused on deaths in the study group of women diagnosed during their 40s, whether they died then or years later. The issue with screening, after all, is whether diagnosis at an earlier time (in this case, during their 40s) ends up with better health outcomes than diagnosis later, after the women or physician finds a breast lump. The problem comes in which breast cancer deaths in the control group should be counted. To be comparable, you really want to count all of the deaths of women who would have been diagnosed had they been screened. But some of these control group women will, in the absence of screening, now be diagnosed in their 50s rather than 40s. But not all women diagnosed with breast cancer in their 50s in the control group would have been diagnosed by screening in their 40s. So which ones should we count and which ones not? In an RCT, one can determine this by waiting for a time after screening stops in both groups and then, when breast cancer cases in the control group "catch up" with cases in the screen group, you have comparability. But in the Swedish type of study design, there is no way to do that. What this means, then, is that further statistical "adjustments" must be done. The Swedish investigators added or subtracted (they don't tell us how they did this) person-years from the denominator of the study group to adjust. But, as noted above, it is very easy to make those adjustments in a way that favors your point of view.

The end result is that it is really difficult to have confidence in the analyses of this group, and the results of this study. There are just too many ways that the adjustments could bias the final result into the desired direction.

So I think this study points out the many problems of this study design, and the potential for bias in the analysis. Again, I would call for an independent group without a preformed point of view to analyze such data. (Something similar happened with prostate cancer screening in the Tyrol study.)"