What's Best for the Breast?

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH

Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips is a consultant for Cephalon, and serves on the speakers for Resmed and Respironics.

Synopsis: In a very large Norwegian study, use 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 in death rate.

Source: Kalager M, et al. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med 2010;363:1203-1210.

This paper is largely the product of an analysis of the Cancer Registry of Norway, which conducts a breast cancer screening program. As part of this program, all women in the country between the ages of 50 and 69 years have been offered screening mammography every 2 years since 2005. In addition, the breast cancer program required the establishment of multidisciplinary breast cancer management teams and breast units in all of the 19 counties in Norway; these teams consist of radiologists, radiologic technologists, pathologists, surgeons, oncologists, and nurses who manage the care of all breast cancer patients. Overall, about three-fourths of the women who were invited chose to participate in the program. The screening mammograms included two views, which were independently read by two radiologists.

For purposes of this analysis, the authors defined four groups of women with breast cancer: two current groups (diagnosed between 1995 and 2005), some of whom had undergone screening (screening group) and some who had not (nonscreening group), and two historical-comparison groups (diagnosed between 1986 through 1995), before screening was offered.

Based on the timing of implementation of the screening program in each county, the authors grouped the 19 counties into six regions; each county within a given region entered the program at approximately the same time. Death rates were calculated separately for each region. First, the authors compared women in the nonscreening groups with their historical counterparts to determine changes in mortality that most likely resulted from improved treatment and earlier clinical diagnosis. Then they compared women in the screening group with their historical counterparts to determine the change in mortality after implementation of the screening program. In this second comparison, the difference in the rate of death between the two groups was attributed both to the screening program and to improved treatment, so the reduction in mortality that was related to the screening program was the difference between the rate ratio for death among women in the screening group as compared with their historical counterparts and the rate ratio for death among women in the nonscreening group as compared with their historical counterparts.

The investigators estimated rates of death from breast cancer in the four study groups according to the age at diagnosis (20-49 years, 50-69 years, and 70-84 years).

A total of 40,075 women were first diagnosed with breast cancer between 1986 and 2005. During the follow-up period, 4791 of these women (12%) died from breast cancer. Of the women who died, 423 (9%) had received the diagnosis after the introduction of the screening program. The average time of follow-up (from diagnosis) was 2.2 years, with a maximum of 8.9 years. Among women between the ages of 50 and 69 years (the age group that was offered mammography), 6967 received a diagnosis of breast cancer between 1986 and 1995, as compared with 12,056 who received the diagnosis between 1996 and 2005. In the latter group, for women between the ages of 50 and 69 years in the screening group, the rate of death was 18.1 per 100,000 person-years, as compared with 25.3 per 100,000 person-years among their historical counterparts, for a difference of 7.2 deaths per 100,000 person-years (a relative reduction of 28%).

Among women in the nonscreening group, the rate of death was 21.2 per 100,000 person-years, as compared with 26.0 per 100,000 person-years among their historical counterparts, for a difference of 4.8 deaths per 100,000 person-years, a relative reduction of 18%.

When the authors factored in the reduction in mortality among women in the nonscreening group, as compared with their historical counterparts, the relative reduction among women in the screening group was 10%. The authors concluded that since the differences between the current groups and historical groups were 7.2 deaths per 100,000 person-years in the screening group and 4.8 deaths per 100,000 person-years in the nonscreening group, only the overall between-group difference — 2.4 deaths per 100,000 person-years could be attributed to the screening program alone, representing a third of the total estimated reduction in mortality (2.4 of 7.2).

Among women between the ages of 50 and 69 years in the screening group, those with stage I tumors had a relative reduction in mortality of 16% compared to historical counterparts; among women in the nonscreening group, the corresponding reduction was 13%. Among women with stage II tumors, those in the screening group had a marked 29% reduction in mortality compared to their historical counterparts; among women in the nonscreening group, the reduction was 7%. Among women with stage III or IV tumors, the improvement in prognosis was similar with and without the screening program.

Among women who were not eligible for screening because they were younger than 50 years of age or older than 69 years of age, there was also a significant reduction in the rate of death from breast cancer compared to historical counterparts; the authors attributed this reduction to multidisciplinary breast-cancer management teams. Among women younger than the age of 50 years, there was a nonsignificant relative increase in mortality of 4% (P = 1.00) after the introduction of the screening program. Among women who were 70 years of age or older, the relative reduction in mortality of 8% (P = 0.09) could be attributed to the establishment of multidisciplinary teams in the screening program.

The authors concluded, "...the take-home message is that breast-cancer screening was associated with an absolute reduction of 10 percentage points in the rate of death from breast cancer. However, the screening program accounted for only one third of the total reduction in mortality ... For women between the ages of 50 and 69 years, it was impossible to determine whether the reduction in mortality resulted from earlier diagnoses associated with screening mammography or from the management of treatment by an interdisciplinary team. To our surprise, the reduction in breast-cancer mortality among women between the ages of 70 and 84 years was largely the same as that in the screening group."

Commentary

First of all, the good news is that breast cancer mortality is most definitely falling. The issue here is whether or not mammography screening contributes significantly enough to improved survival to justify the cost, stress, radiation exposure, and false-positives. An analysis in the United States of breast cancer death from 1975 through 2000 concluded that only about half the observed reduction in mortality resulted from mammography; the rest was attributed to better management of the disease after diagnosis.1 This current report, indicating that the contribution to reduced death from breast cancer from mammography is only about a third of the total overall reduction, adds considerably to the ongoing debate about screening in general, and breast cancer screening in particular. It confirms that the benefit from screening, compared to post-diagnosis care, is small.

Another issue with regard to screening relates to which age groups are most likely to benefit from mammography. About a decade ago, the World Health Organization recommended screening mammography for women between the ages of 50 and 68 years, based on data suggesting a 25% reduction in death rates from breast cancer with this approach.2,3 Indeed, based on that recommendation, the approach in Norway (the source of the current paper) has been to offer mammography only to those in that age group. Not so in the United States where mammography has been advocated and offered to women older than age 40. However, nearly a year ago, the U.S. Preventive Services Task Force (USPSTF) recommended against routine screening mammography in women aged 40-49 years, and recommended biennial (rather than annual) screening mammography for women between the ages of 50 and 74 years.4 It also concluded that evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older.

Now, after years spent trying to get women to undergo mammograms, clinicians have found themselves backpedalling in the wake of this USPSTF recommendation. The current report from Norway seems to indicate the benefits of screening, even in the 50- to 69-year-old group, may be slim.

So, what should we tell our patients? Perhaps the most important message here is that we cannot afford to be dogmatic about breast cancer screening (or anything else, for that matter). This is clearly not yet a black and white issue. The possible benefits of screening need to be carefully balanced against the very real negatives, including cost, angst, radiation exposure, and unnecessary follow-up testing due to false-positives.

References

1. Berry DA, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 2005;353:1784-1792.

2. Miller AB, et al. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ 1992;147:1477-1488.

3. Nystrom L, et al. Breast cancer screening with mammography: Overview of Swedish randomised trials. Lancet 1993;341:973-978.

4. U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009; 151:716-726, W-236.