|The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up.|
|Tuesday, 03 September 2002 00:00|
"BACKGROUND: The efficacy of breast cancer screening in women age 40 to 49 years remains controversial. OBJECTIVE: To compare breast cancer mortality in 40- to 49-year-old women who received either 1) screening with annual mammography, breast physical examination, and instruction on breast self-examination on 4 or 5 occasions or 2) community care after a single breast physical examination and instruction on breast self-examination. DESIGN: Individually randomized, controlled trial. SETTING: 15 Canadian centers. PARTICIPANTS: 50 430 volunteers age 40 to 49 years, recruited from January 1980 to March 1985, who were not pregnant, had no previous breast cancer diagnosis, and had not had mammography in the preceding 12 months. INTERVENTIONS: Breast physical examination and instruction on breast self-examination preceded random assignment of 25 214 women to receive mammography and annual mammography, breast physical examination, and breast self-examination and 25 216 women to receive usual community care with annual follow-up. MEASUREMENTS: Verified breast cancer incidence and cohort mortality through 31 December 1993 and deaths from breast cancer through 30 June 1996. RESULTS: The 105 breast cancer deaths in the mammography group and 108 breast cancer deaths in the usual care group yielded a cumulative rate ratio, adjusted for mammography done outside the study, of 1.06 (95% CI, 0.80 to 1.40). A total of 592 cases of invasive breast cancer and 71 cases of in situ breast cancer were diagnosed by 31 December 1993 in the mammography group compared with 552 and 29 cases, respectively, in the usual care group. The expected proportions of nonpalpable and small invasive tumors were detected on mammography. CONCLUSION: After 11 to 16 years of follow-up, four or five annual screenings with mammography, breast physical examination, and breast self-examination had not reduced breast cancer mortality compared with usual community care after a single breast physical examination and instruction on breast self-examination. The study data show that true effects of 20% or greater are unlikely."
"The Canadian National Breast Screening Study-1 (CNBSS-1), an individually randomized trial in women 40 to 49 years of age at study entry, evaluated the efficacy of annual mammography, breast physical examination, and instruction on breast self-examination in reducing breast cancer mortality. The 7-year and preliminary 10-year mortality results were previously reported. At 7 years, 38 women in the mammography group and 28 women in the usual care group had died of breast cancer, for a rate ratio of 1.36 (95% CT, 0.84 to 2.21). At 10 years, there were 82 breast cancer deaths in the mammography group and 72 in the usual care group (rate ratio, 1.14 [CI, 0.83 to 1.56]). This article reports CNBSS-1 results after an average 13-year follow-up from study entry."
"In CNBSS-1, combined screening of women age 40 to 49 years with annual mammography and breast physical examination for up to 5 years did not reduce breast cancer mortality compared with women who had a single breast physical examination and subsequent care from Canada's universal health care system. We would not expect this null result to be explained by the instruction of both groups in breast self-examination, although such instruction may benefit younger women."
"CNBSS-1 was planned to evaluate whether breast cancer mortality would decrease by 40% in the mammography group compared with the usual care group after 5 years of follow-up. In the late 1970s, expectations for breast screening efficacy in this age group were high despite early negative findings in the Health Insurance Plan trial. Our null result is consistent with findings from the Östergötland and Stockholm trials. Furthermore, the initial nonsignificant excess in breast cancer mortality in screened women that we previously reported was also observed in the Swedish Two County trial. However, the lower 95% CI for reduction in breast cancer mortality in CNBSS-1 does not include the 18% reduction derived from the most recent meta-analysis of screening trials. Nevertheless, this meta-analysis included trials that only randomly assigned women 45 to 49 years of age, and much of the benefit could be due to the screening of women older than 50 years of age. Thus the true effect of mammography screening of women in their forties is likely to be small."
"... why have trials consistently shown increased breast cancer mortality in screened women 40 to 49 years of age soon after screening begins? This may relate to premenopausal status, tumor status at time of diagnosis, and tumor growth factors."
"Another important issue is whether mammography screening leads to "overdiagnosis" of breast cancer - that is, the detection of a tumor that would not have become clinically detectable in the patient's lifetime. Lobular carcinoma in situ is usually considered a marker of breast cancer risk, and ductal carcinoma in situ should probably be regarded similarly. Overdiagnosis of in situ breast cancer has been documented previously. CNBSS-1 provides evidence that overdiagnosis of nonpalpable invasive breast tumors may also occur. Figure 2 shows that unless the lead time gained by mammography exceeds 10 years, an excess 40 cases of invasive breast cancer detected by mammography persist. This represents 58% of the 69 cases of nonpalpable invasive breast cancer in the mammography group and 70% of the nonpalpable (69 nonpalpable and 42 in situ) tumors in the mammography group. This proportion is greater than the 50% of cases of in situ plus invasive cancer detected by screening in the mammography group that meet the definition of minimal breast cancer (in situ plus invasive tumors < 10 mm in diameter). Detection of minimal breast cancer was a main objective for early breast screening programs and was expected to provide the main benefit of mammography screening. The null results for CNBSS-1 and CNBSS-2 place substantial doubt of such claims. More breast cancers were detected in the mammography group than in the usual care group, but breast cancer mortality did not differ between the groups."
"CNBSS-1 is the only trial designed to assess screening in women 40 to 49 years of age, and its merits were recognized in a recent review. Until the ongoing United Kingdom trial of women recruited at ages 40 to 41 years reaches fruition, it will be uncertain whether women in their forties benefit from mammography. Women younger than 50 years of age should understand that in the setting of physician breast examination, breast self-examination, diagnostic mammography, and effective cancer therapy, the benefits of screening mammography are uncertain. Women must also consider the adverse consequences of false-positive mammograms."