Editorials

Breast cancer screening in women aged under 50

Although there is a reasonably strong consensus that screening for breast cancer saves lives among women aged 50-69, debate is fierce about the effect in women aged 40-49. The debate is particularly strong in North America. The American Cancer Society, American Medical Association, and American College of Radiology recommend that screening should begin at age 40, while the United States Preventive Services Task Force, American College of Physicians, and Canadian Task Force on the Periodic Health Examination recommend starting at age 50. In 1993 the United States National Cancer Institute stepped back from its recommendation to begin at age 40 after reviewing the most up to date data from the seven randomised trials conducted in Edinburgh, Sweden, the United States, and Canada. The report of the institute's international workshop concluded: "For (women aged 40-49 years) it is clear that in the first five to seven years after study entry, there is no reduction in mortality from breast cancer that can be attributed to screening. There is an uncertain, and if present, marginal reduction in mortality at about 10-12 years. Only one study (Health Insurance Plan) provides information on long term effects beyond 12 years, and more information is needed."¹

In January, with four more years of follow up from these trials available, the National Institutes of Health convened a consensus development conference on breast cancer screening in women aged 40-49. After reviewing the literature and hearing presentations from 32 experts, the independent panel concluded that "at the present time, the available data do not warrant a single recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography. Given both the importance and complexity of the issues involved in assessing the evidence, a woman should have access to the best possible information in an understandable and usable form."²

The dilemma for women in their 40s is that randomised trials of breast cancer screening have, on the one hand, found slower and smaller benefits and, on the other, found more frequent adverse effects than in older women. A meta-analysis found that, whereas mortality from breast cancer decreased among older women by about a third within seven years of study entry, mortality in screened and control groups among younger women was almost identical throughout the first seven years.³ Recently, a repeat meta-analysis, with 10-15 years of follow up data, found a 15% reduction in mortality among younger women invited for screening (ratio=0.85, 95% confidence interval 0.71 to 1.01).⁴

Why the slow and small benefit? At the consensus conference, Tabar presented data suggesting that some cancers in younger women spread faster and argued that younger women must be screened yearly for optimal effect. Others have pointed out that all trial analyses are done according to age at entry, not age at diagnosis.⁵ Because the incidence of breast cancer increases with age and because women age during a trial, it has been suggested that some of the delayed benefit of screening is due to cancers detected through screening when women reach their 50s and menopause. Three trials reviewed at the conference found that about a third of cancers among women in their 40s were detected after the women turned 50. The NHS breast screening programme now under way in Britain⁶ avoids this "age-creep" problem by entering women at ages 40 and 41 and screening for five years, thus ensuring that all cancers are detected during the 40s.

Important adverse effects reviewed at the conference included false negative and false positive mammograms and possible overdiagnosis because of ductal carcinoma in situ. All these problems were more frequent in younger women: screening misses up to a quarter of cancers in younger women (compared with a tenth in older women), and the false positive rate is higher in younger women, leading to more benign biopsies, increased costs,⁷ and greater anxiety.⁸ The percentage of mammograms read as abnormal (and the resultant percentage of false positive mammograms) varies by country. In the United States, about 11% of mammograms are read as abnormal,⁹ compared with fewer than 5% in the Edinburgh and Swedish trials.¹ Proponents of screening suggest that technical improvements in mammography should mitigate the problems of false negative and false positive results. Again, the ongoing British trial will help determine if this is so.

Ductal carcinoma in situ is a more difficult problem because it is not clear how often it progresses to invasive cancer. In one study ductal carcinoma in situ accounted for 43% of cancers detected by mammography in women in their 40s.¹⁰ It may be that detection of ductal carcinoma in situ has led to overdiagnosis and is at least partly responsible for the increased incidence of breast cancer.¹¹

There are few places in the developed world where a large scale trial could still be carried out to sort out these questions about breast cancer screening. As time goes on and questions remain about the usefulness of screening women in their 40s for breast cancer, the wisdom of the organisers of the British trial becomes increasingly apparent.

Suzanne Fletcher, Professor ^a

^a Department of Ambulatory Care and Prevention, Harvard Medical School, Boston, MA 02215, USA

1. Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 1993;85:1644-56. [Abstract/Free Full Text]
2. Draft NIH Consensus Statement. Breast cancer screening for women ages 40-49. http://odp.od.nih.gov/consensus/statements/cdc/103/103_stmt.html.
3. Elwood JM, Cox B, Richardson AK. The effectiveness of breast cancer screening by mammography in younger women. Online Journal of Current Clinical Trials 1993.
4. Report of the Organizing Committee and Collaborators, Falun Meeting, Falun, Sweden 21 and 22 March, 1996. Breast cancer screening with mammography in women aged 40-49 years. Int J Cancer 1996;68:693-9.
5. Kerlikowske K, Grady D, Rubin SM, Sandrock C, Ernster VL. Efficacy of screening mammography. A meta-analysis. JAMA 1995;273:149-54. [Abstract]
6. Moss SM, Michel M, Patnick J, Johns L, Blanks R, Chamberlain J. Results from the NHS breast screening programme 1990-1993. J Med Screen 1995;4:186-90.
7. Lidbrink E, Elfving J, Frisell J, Jonsson E. Neglected aspects of false-positive findings of mammography in breast cancer screening: analysis of false-positive cases from the Stockholm trial. BMJ 1996;312:273-6. [Abstract/Free Full Text]
8. Lerman C, Tock B, Rimer B, Boyce A, Jepson C, Engstrom PF. Psychological and behavioral implications of abnormal mammograms. Ann Intern Med 1991;114:657-61.
9. Brown ML, Houn F, Sickles EA, Kessler L. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR 1995;165:1373-7.
10. Kerlikowske K, Grady D, Barclay J, Sickles EA, Eaton A, Ernster V. Positive predictive value of screening mammography by age and family history of breast cancer. JAMA 1993;270:2444-50.
11. Ernster VL, Barclay J, Kerlikowske K, Grady D, Henderson C. Incidence of and treatment for ductal carcinoma in situ of the breast. JAMA 1996;275:913-8. [Abstract]