Should We Recommend Screening Mammography for Women Aged 40 to 49?
Should We Recommend Screening Mammography for Women Aged 40 to 49?
Esserman and Kerlikowske have done an excellent job in reviewing the factual information on screening mammography for women age 40 to 49 years. Their review builds on some previously published work by Kerlikowske and colleagues, particularly their meta-analysis . This meta-analysis was important, in that it addressed the issue of timing in relation to mammography screening in women 40 to 49 years old, as compared with those 50 to 69 years of age. The combined data of eight randomized trials clearly demonstrated that there was absolutely no benefit of mammography for women age 40 to 49 at 7 to 9 years after the initiation of screening. In contrast, for women age 50 to 69, there was a substantial and statistically significant reduction in breast cancer mortality.
Over the period of 10 to 12 years from the initiation of screening, there was some suggestion of a nonsignificant reduction in mortality for women 40 to 49 years old, but this was nowhere near as great as the persistence of a similar order of benefit at 10 to 12 years as for 7 to 9 years for women age 50 to 69. The meta-analysis therefore demonstrated the continued validity of a conclusion we reached 5 years before; namely, that there is no evidence of benefit from screening women in their 40s, at least in the first 10 years after the initiation of screening .
Delayed Benefit Seems Biologically Implausible
Although several researchers continue to dispute the lack of benefit in the younger age group and suggest that it is not unreasonable for a delayed benefit to occur from screening, they are un able to convince us of the validity of these beliefs, largely because there does not seem to be a biologic reason why there should be a greater delay for seeing benefit from screening in younger compared to older women. In addition, much of the data have accrued from women who commenced screening at age 45 to 49, and a delayed benefit in relation to the initiation of screening at these ages is entirely compatible with the anticipated effect of screening when women reach the age of 50. This point is well considered by Esserman and Kerlikowske, who refer to the important work by De Koning et al  in modeling expected benefits.
Esserman and Kerlikowske point to a possible reason for the nonsignificant excess breast cancer mortality we observed in the earlier stages of the Canadian National Breast Screening Study (CNBSS), suggesting this may have been due to a delay in diagnosis. We have carefully evaluated our data, and find no evidence of such a delay. One of the reasons for this may have been our teaching and subsequent reinforcement of breast self-examination, a procedure which, on its own, now appears to be providing some benefit to both younger and older women .
Women With a Positive Family History
Esserman and Kerlikowske also discuss the lack of information on the benefit of screening mammography among women with a positive family history. I would add additional caution to their remarks. There may be some risk in using screening to attempt to provide support for such women. There is no reason to believe that women with a positive family history, particularly those carrying breast cancer susceptibility genes, would benefit from screening when women at normal risk do not. Indeed, some have expressed concern that there may be detriments from the use of mammography in women at increased risk--a possibility that we will be evaluating over the next few years using the data on family history accumulated in the CNBSS supplemented by additional data collected from the participants or their relatives.
Physical Exams in Women Aged 40 to 49
In debates over this issue, the point is often made that if mammography is not beneficial in women aged 40 to 49, the trials suggest that physical examination is not either. In practice, the trial evidence cannot be used to draw such a conclusion. One of the trials that suggests a delayed benefit, the HIP trial, used good physical examination but 1960s mammography, and only a fraction of the cancers were diagnosed by mammography alone. None of the Swedish trials used physical examination. In the Edinburgh trial, which suggests a benefit from screening in this age group, physical examinations were performed every year and mammography every 2 years, and yet women were only recruited from the age of 45; therefore, this trial cannot fully evaluate the question.
In the CNBSS, physical examination was given to both groups upon recruitment, and women in the control arm were urged to continue to practice breast self-examination and were reminded annually to do so and to see their own doctor for a physical examination. Thus, the level of physical examination screening in the control group of this trial was probably substantially greater than that in normal practice. What we demonstrated in this younger age group, as we did in the older, is that mammography does not produce a mortality benefit, over and above the physical examination and the practice of self breast-examination. However, we cannot address directly the effect of physical examination.
Additional Costs of Screening
As if the lack of benefit of screen-ing mammography is not enough, Esserman and Kerlikowske point to the additional costs from detecting ductal carcinoma in situ in this age group, as well as the additional biopsies. I would only add that not only were we able to show such adverse effects, and thus, excess health-care costs, but also we found no reduction in the rate of mastectomies in the mammography arm .
Thus, at present the appropriate recommendation for women and their physicians is to practice breast self- examination, have an annual physical examination by a physician or other health professional who knows the signs of early breast cancer, and use mammography if indicated by either of these procedures as a diagnostic tool, but not for routine screening.
1. Kerlikowske K, Grady D, Rubin SM et al: Efficacy of screening mammography: A meta-analysis. JAMA 273:149-154, 1995.
2. Miller AB, Chamberlain J, Day NE et al: Report on a workshop of the UICC Project on evaluation of screening for cancer. Int J Cancer 46:761-769, 1990.
3. De Koning HJ, Boer R, Wannerdain PG et al: Interpretation of age-specific mortality reductions from the Swedish breast cancer screening trials. J Natl Cancer Inst 87:1217-1223, 1995.
4. Harvey BJ, Miller AB, Baines CJ, et al: A case-control study of breast self-examination practice nested in the Canadian National Breast Screening Study. Submitted to NEJM.
5. Miller AB: May we agree to disagree, or how do we develop guidelines for breast cancer screening in women? J Natl Cancer Inst 86:1729-1731, 1994.