Following are brief summaries of the major randomized trials of breast cancer screening. They represent study designs in which a large group of women was randomly assigned to a group that either would or would not receive an invitation to be screened for breast cancer. As can be seen, the first of these studies was initiated in the early 1960s, and for some, follow-up still continues.
Each followed a somewhat different protocol, and the outcome in each has been influenced by a number of factors that have important implications for the interpretation of study results. These factors include the study methodology, the clinical protocol, participation rates in the study group (compliance), screening rates in the control group (contamination), and the number of screening rounds before an invitation was extended to the control group. Other factors that likely influenced end results include the quality of the screening process, thresholds for diagnosis, and follow-up mechanisms for women with an abnormality. For these factors, we have few insights into individual trials.
It is also the case that, with the exception of the randomized trials conducted in Canada (NBSS-I and -II), which, as noted in the description of the Canadian trials below, have been controversial, none was specifically designed to evaluate the efficacy of breast cancer screening in age-specific subgroups (e.g., women aged 40 to 49). The availability of data in each of the trials has provided the opportunity for retrospective analysis of screening efficacy by age; however, limitations in statistical power and questions regarding the appropriateness of applying the same screening protocol to pre- and postmenopausal women have been the focus of debate over whether health policy could reliably be informed by the existing data.
Health Insurance Plan of New York Randomized Clinical Trial
The HIP study was initiated in December 1963. It was the first randomized, controlled trial to evaluate the efficacy of breast cancer screening with CBE and mammography. Approximately 62,000 women aged 40 to 64 were randomly assigned to two groups: The study group would be offered annual CBE and two-view mammography (craniocaudal and mediolateral views) for 4 years, and the control group would receive usual care.
After 10 years from entry into the study, approximately 30% fewer breast cancer deaths occurred in the study group compared with the control group. At 18 years of follow-up, there were 23% fewer deaths. Mammography and CBE contributed independently to breast cancer detection, with 33% of cases detected by mammography alone, 45% with CBE alone, and 22% with combined modalities.
Swedish Two-County Study
The largest randomized trial of breast cancer screening is the Swedish Two-County study, so-called because women were randomized into study and control groups within two counties in Sweden, Kopparberg and Ostergotland. The trial consisted of approximately 133,000 women aged 40 to 74 years, with approximately 77,000 women invited to the screening.
The screening intervals differed by age, with women aged 40 to 49 invited every 24 months and women aged 50 and older invited every 33 months. The screening examination included only single-view mammography (mediolateral oblique view) and did not include CBE. After 8, 11, and 14 years of follow-up, approximately 30% fewer breast cancer deaths occurred in the study group invited to the screening compared with the control group.