Family Practice Vol. 17, No. 3, 272-275
© Oxford University Press 2000
Selections from Current Literature |
Mammography screening for breast cancer in women under 50 years
Department of Family Medicine, Health Sciences Center L-4, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Sussman HR. Mammography screening for breast cancer in women under 50 years. Family Practice 2000; 17: 272–275.
This instalment of ‘Selections from current literature’ tackles an issue that is both important and controversial: mammography screening for breast cancer in women under 50 years old. The articles reviewed were chosen as the most up-to-date evidence available. As such, the information contained herein may enable the family physician to apply population-based epidemiology to an individual setting. Thus, the doctor and patient may make informed decisions about this highly personal, vitally important topic.
Antman K, Shea S. Screening mammography under age 50. J Am Med Assoc 1999; 281: 1470–1472.
In this article, the authors chronicle the history of breast cancer screening recommendations. Upon completion of the first six randomized mammography trials in 1989, the American Cancer Society, the National Cancer Institute (NCI) and various other organizations issued joint recommendations for women aged 40–75 years. Subsequent analysis, however, demonstrated negligible benefit in the 40- to 49-year-old subgroup. This was in striking contrast to patients 50 years and older, for whom an overall 25–30% reduction in breast cancer mortality was observed. In 1992, Canadian investigators reported no significant benefit for mammography in women aged 50–59 years and a statistically insignificant excess of breast cancer mortality in the mammography group in women aged 40–49 years. Contributing to the confusion was the fact that the design, sampling and results of the Canadian studies have been considered flawed by several experts. The NCI reconsidered in 1993. Based on the collective data available, the NCI came out against screening mammography prior to age 50 years. In 1997, new evidence showed a genuine improvement in mortality rates for women aged 40–49 years. The new data also refuted the hypothesis that this benefit was attributable to length–time bias. Recent meta-analysis of all published studies showed varying results depending on the use of the Canadian data. An insignificant 16% became a statistically significant 24% decreased mortality in women aged 40–49 years when the Canadian data were excluded.
The authors highlight a wide array of opinions from the literature ranging from "don't screen any women" to "screen all beginning at age 40 years", including some of the justifications for the various assertions along this continuum. One of the rationales emphasized was a comparison of women in their forties versus women in their sixties based on the number needed to screen to save one life. Combined data from the randomized trials demonstrate one extended life in 1700 screening mammograms for women 60–69 years old. This contrasts with the 5000 mammograms required in order to extend the life of one 40- to 49-year-old. The authors discuss a study that estimates the rate of false-positive mammograms at 24%. The consequences of these erroneous mammograms included many unnecessary repeat views, ultrasounds and biopsy procedures. However, they point out that attempting to diminish the ratio of negative biopsies by deferring the procedure in cases of intermediate likelihood would probably be deemed unacceptable by patients. In conclusion, the authors offer a ‘reasonable recommendation’ that women might begin screening between ages 45 and 50 years.
Comment
Mammography under age 50 years is controversial for several reasons. The media have played a role and, in turn, the lay public may be confused or may derive opinions that are not supported by hard evidence. Politics of course have entered into it. Fear of litigation and so-called defensive medicine may factor in as well. In addition, there may exist a mentality that no price is too high to ensure one's health. Conflicting guidelines abound depending upon which organization or authority one consults. The US Preventive Services Task Force1 has given an ‘A’ recommendation to screening mammography every 1–2 years, with or without clinical breast examination, for women aged 50–69 years. However, mammography for women aged 40–49 years garners only a ‘C’ recommendation. Similarly, the American Academy of Family Physicians (AAFP)2 suggests that women aged 40–49 years should receive counselling regarding potential risks and benefits of mammography and clinical breast examination. Yet the AAFP considers mammography and clinical breast examination every 1–2 years to be the standard of practice for women aged 50–69 years. The American Cancer Society3 and the American College of Radiology4 recommend that women aged 40 and over should have annual mammograms and clinical breast examinations. The NCI5 encourages women aged 40 years and over to have mammography and clinical breast examination every 1–2 years. The American College of Obstetricians and Gynecologists6 are proponents of mammography every 1–2 years in women aged 40–49 years and annual mammography in women aged 50 and over. Another variation on this theme comes from the American College of Physicians1 who make a positive recommendation for women aged 50–74 years to have a mammography every 2 years, but a negative recommendation for baseline mammograms or mammograms for women under 50 or over 75 years.
Alexander FE, Anderson TJ, Brown HK et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–1908.
The authors report the results from the Edinburgh randomized trial of breast cancer screening after 14 years of follow-up. The purpose of the study was to compare breast cancer mortality rates between women receiving regular screening and controls. The study authors hypothesized that breast cancer mortality would be lower in the intervention group than in the control group. Women in the intervention group received annual clinical breast examination and two-view mammography every 2 years, whereas control group women received routine medical care alone. Three distinct cohorts were created. Between 1978 and 1981, 44 288 women aged 45–64 years were recruited from 87 general practices in Edinburgh (cohort 1). Subsequently, 10 366 women aged 45–49 years became eligible during the periods 1982–1983 (cohort 2) and 1984–1985 (cohort 3). Participating practices were randomized after stratification by number of physicians in order to balance the number of subjects between the two groups. Patients were analysed in the groups to which they were randomized. There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit. Other cause mortality rates were statistically similar when adjusted for socio-economic status. The study concluded in 1988. Approximately 98% of all women in the trial were followed-up 14 years later. Initially, a mere 13% benefit was demonstrated between the control and intervention groups. However, adjustment for socio-economic status and exclusion of deaths after diagnosis beyond 3 years after the end of the study produced a mortality rate ratio of 0.71 (95% CI 0.53–0.95). In other words, an overall 29% improvement in mortality with screening was shown. It is of note that the difference in breast cancer mortality between intervention and control groups for the youngest women (45–49 years) was 30% in the initial cohort and 25% in all cohorts combined. The authors conclude that their findings confirm the overall advantage of screening for breast cancer as previously reported from Swedish and American studies. The results for younger women suggest benefit from introduction of screening before 50 years of age.
Comment
The sensitivity of mammography is variable, with multiple factors having an influence. Recent advances in technique should enhance sensitivity, which is currently 75% for women aged 50–59 years.7–10 The combination of clinical breast examination and mammogram has 75–88% sensitivity. These rates are 10–15% lower for women aged 40–49 years. Similarly, the specificity is also increasing with improved technique. Specificity has ranged from 83% in Canadian studies11 to 98.5% in the USA.12 Here again, a 10–15% decrease is observed for women in their forties. Interestingly, half as many cancers are detected in women aged 40–49 years compared with 50- to 59-year-olds. Yet 40- to 49-year-olds underwent twice as many diagnostic tests per cancer detected.13 Furthermore, 30% of women screened annually in their forties will have at least one false-positive mammogram.14
UK Trial of Early Detection of Breast Cancer group. 16-Year mortality from breast cancer in the UK Trial of Early Detection of Breast Cancer. Lancet 1999; 353: 1909–1914.
The purpose of this study was to investigate the effects on mortality of screening mammography, clinical breast examination and breast self-examination. Designed in 1979, this study's data have been updated after 16 years of follow-up. More than 98% of the originally identified participants were traced successfully. The Trial of Early Detection of Breast Cancer was not randomized, but rather compared eight distinct regions in the UK. Screening occurred at two of these centres. Breast self-examination was taught at two other centres. Four centres remained without intervention for the purpose of comparison. The initial cohort consisted of 45 607 women screened, 63 373 women educated regarding self-examination and 127 123 controls. Subsequent cohorts contained additional subjects in the 45- to 49-year age range. Overall, 127 487 women represented the younger age group in question. Possibly due to varying socio-economic status, the geographically separate districts demonstrated different underlying breast cancer incidence and mortality rates. In order to adjust for possible confounding, pre-trial standardized mortality ratios were calculated. Analysis by age at entry was done for 5 year age groups. However, because the group of 45- to 46-year-olds formed a large proportion of the women aged 45–49 years, and because it was relevant to questions of the age at which screening should begin, the youngest subgroup was also analysed separately. For screening centres, the overall point estimate of breast cancer mortality reduction (after adjustment for pre-trial mortality) was 0.73 (95% CI 0.63–0.84). This ~27% benefit was borne out similarly when deaths in cases diagnosed within 10 years of entry were included. It is of note that a statistically significant 30% mortality reduction was observed by screening women aged 45–49 years. Furthermore, the reduction attributed to screening was 35% in the youngest subgroup of women aged 45–46 years. No significant difference between the rate ratios for the various age groups or between initial and subsequent cohorts was seen. The authors noted no reduction in breast cancer mortality at the breast self-examination centres. The cumulative mortality rates for screening centres versus controls were seen to begin divergence at about 5–6 years from the start of the investigation. They continued to diverge to year 16. Such divergence was detected earlier for the 45- to 49-year-old group (at years 3–4) than for the 50- to 54-year-old group (year 10). The authors suggest that screening from age 45 years may be at least as effective as starting from 50 years.
Comment
There are essentially four criteria for a screening test: (i) the disease being screened for should be common; (ii) the disease should cause significant morbidity; (iii) an accurate and acceptable test should be available (in this context acceptability refers to the cost, convenience and tolerability of the test from the perspective of both the patient and the physician); and (iv) early diagnosis should be beneficial. The burden of suffering from breast cancer is staggering.15 An estimated 175 000 new cases of breast cancer were diagnosed in women in the USA in 1999. Twenty-nine per cent of all diagnosed malignancies in females will have affected the breast. An estimated 43 300 deaths in women in the USA were due to breast cancer in 1999, accounting for 16% of all cancer mortality in women. Overall, breast cancer will rank first among cancers diagnosed and second among cancers causing death in women. The risk of developing breast cancer increases sharply with age.16 For women younger than 39 years, the frequency is 1 in 231. Women aged 40–59 years have a 1 in 25 chance. Sixty- to seventy-nine-year-olds are diagnosed once out of every 15 patients. In total, 1 in every 8 women (12.5%) will develop breast cancer in the span of their lifetime. The age interval in question—from 40 to 49 years—carries a 10 year risk of developing breast cancer of 1.58% (1 in 63).
Summary
The benefit of screening mammography for women older than 50 years is incontrovertible and has been widely accepted for many years. However, the data for women under 50 years have been less clear. A contemporary view of this historical controversy has been depicted, including a chronology of varying recommendations. Discrepancies in various organizations' current guidelines have been highlighted. As family physicians, we turn to the most recent scientific evidence in order to choose the most appropriate course of action. Recent data from important long-term British trials have been reported. In light of these revelations, it now seems apparent that screening mammography can significantly reduce breast cancer mortality for women in their forties.
References
1 US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd edn. Baltimore: Williams & Wilkins, 1996.
2 American Academy of Family Physicians. Age Charts for Periodic Health Examination. Kansas City, MO: American Academy of Family Physicians, 1999.
3 American Cancer Society. Mammography Guidelines for Asymptomatic Women. Atlanta, GA: American Cancer Society, 1997.
4 American College of Radiology. ACR Standards. Reston, VA. American College of Radiology, 1998.
5 National Cancer Institute. Screening Summary for Breast Cancer. Bethesda, MD. National Cancer Institute, 1999
6 American College of Obstetricians and Gynecologists. Primary Care Review for the Obstetrician–Gynecologist: Primary and Preventive Care. Washington, DC: American College of Obstetricians and Gynecologists, 1997.
7
Fletcher SW, Black W, Harris R et al. Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 1993; 85: 1644–1656.
8
Robertson CL. A private breast imaging practice: medical audit of 25,788 screening and 1,077 diagnostic examinations. Radiology 1993; 187: 75–79.
9 Peeters PH, Verbeek AL, Hendricks JH et al. Screening for breast cancer in Nijmegen. Report of 6 screening rounds, 1975–1986. Int J Cancer 1989; 43: 226–230.[ISI][Medline]
10 Tabar L, Faberberg G, Day NE et al. What is the optimum interval between mammographic screening examinations? An analysis based on the latest results of the Swedish two-county breast cancer screening trial. Int J Cancer 1987; 55: 547–551.
11 Miller AB, Baines CJ, To T et al. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. Can Med Assoc J 1992; 147: 1477–1488.[Abstract]
12 Shapiro S, Venet W, Strax P et al. (eds). Periodic Screening for Breast Cancer. Baltimore: Johns Hopkins University Press, 1988.
13 Kerlikowske K, Grady D, Barclay J et al. Positive predictive value of screening mammography by age and family history of breast cancer. J Am Med Assoc 1993; 270: 2444–2450.[Abstract]
14 Harris R. Variation of Benefits and Harms of Breast Cancer Screening With Age. Journal of the NCI Monographs No. 22, 1997.
15 Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. Calif Cancer J Clin 1999: 49: 8–31.
16 Feuer EJ, Wun LM, Boring CC, Flanders WD, Timmel MJ, Tong T. The lifetime risk of developing breast cancer. J Natl Cancer Inst 85: 892–897.
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