6. Estado de la cuestión
6.4. La animación seriada
Screening8refers to the process of identifying unrecognized disease in apparently healthy individuals [53]. The purpose of mammography screening is to detect breast cancer in a sufficiently early stage to improve its prognosis: compared to a situation without screening, where breast cancer would be detected as a consequence of symptoms, detection of pre-symptomatic cancers at screening will enable treatment in a more frequently curable stage [54]. In 1968, the World Health Organization described 10 principles for screening that would indicate the usefulness of a screening program for a specific disease [53]:
1) The condition sought should be an important health problem
2) There should be an accepted treatment for patients with recognized disease 3) Facilities for diagnosis and treatment should be available
4) There should be a recognizable latent or early symptomatic stage 5) There should be a suitable test or examination
6) The test should be acceptable to the population
7) The natural history of the condition, including development from latent to declared disease, should be adequately understood
8) There should be an agreed policy on whom to treat as patients
9) The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole
10) Case-finding should be a continuing process and not a "once and for all" project
1.2.2 General definitions and concepts
The time between when a cancer is found through screening and the time it would have been found due to symptoms is termed lead time9. The time from when a cancer is detectable through screening and the time it would be detected due to symptoms is termed
8Screening is any examination that aims to detect unrecognized disease in apparently healthy individuals. 9
Lead time is the time between the detection of breast cancer at screening and the time that the tumor
would be detected if screening had not occurred, i.e. the amount of time that the date of diagnosis is advanced by screening.
sojourn time10, which is the maximal lead time for a given tumor. Sojourn time is expected to vary for different tumors, in line with the heterogeneity of breast cancer [54]. The sojourn time is also dependent on how early in the natural history the screening test is able to detect the tumor. In practice, neither sojourn times nor lead times are directly observable, and their distributions are therefore largely unknown. Long sojourn times imply higher chances of being detected at screening [54].
In mammography screening for breast cancer, the mammography examination in itself is not the final step in the diagnostic process. Women that are considered to have an abnormal mammogram are recalled for further investigation, and the diagnosis of cancer requires invasive procedures such as a biopsy. In consequence, the terms defined below do not refer to a single diagnostic test, but rather a sequence of diagnostic tests starting with mammography and proceeding to biopsy if necessary. Women who have an abnormal mammogram and who turn out to have breast cancer are classified as having
true positive tests (‘a’ in the Table 1 below). An abnormal mammogram followed by
normal subsequent tests is termed false positive (‘b’). When breast cancer is present, but is not detected at mammography, the mammography is classified as a false negative mammogram (‘c’). If there is no breast cancer and the mammogram is normal, the mammography examination is termed true negative (‘d’).
10Sojourn time is time from a breast cancer is detectable by the screening test to the time when the cancer
The sensitivity11 of mammography screening refers to the ability of mammography examination to correctly identify women who through subsequent tests turn out to have breast cancer, i.e. the proportion of true positives among the combined number of true positives and false negatives. The specificity12 of mammography screening refers to the ability of mammography examination to correctly identify women without breast cancer, i.e. the proportion of true negatives among the combined number of true negatives and false positives. The predictive value of a positive test13 (PV+) is the probability that a recalled woman will get a breast cancer diagnosis after subsequent tests, i.e. the number of true positives among all (true and false) positives.
The time between two screening examinations is termed the screening interval14. The European guidelines for screening programs defines interval cancers15as cancers that are detected in this time period in women who attended screening and had normal mammograms or normal recall investigations, or in a time period equal to the screening interval for women who have reached the upper age limit for screening [55]. As a group, interval cancers will consist of cancers that were missed at screening (false negatives) and cancers that were not detectable at screening, but reached a symptomatic stage before the next scheduled screening. The latter group will have short sojourn times and more aggressive growth patterns than cancers detected at screening [54].
The first screening round is often termed the prevalence screening16. The term may be used to describe the first screening in a population during screening
implementation, or the first screening for an individual. When screening is implemented, women in the entire screening age range will have a prevalence screening. In a fully
11The sensitivity of a test is the ability of the test to correctly identify those individuals who have the
disease that is being tested for. Sensitivity is calculated as the number of true positive tests divided by the number of true positive and false negative tests and expressed as a proportion or a percentage.
12The specificity of a test is the ability of the test to correctly identify those individuals who do not have the
disease that is being tested for. Specificity is calculated as the number of true negative tests divided by the number of true negative and false positive tests and expressed as a proportion or a percentage.
13The predictive value of a positive test is the probability that an individual with a positive test truly has the
disease that is being tested for.
14
The screening interval is the time between two screening examinations. In the Norwegian Breast Cancer
Screening Program, the screening interval is two years.
15Interval cancers are cancers that are detected during the screening interval in women who attended
screening and had normal mammograms or normal recall investigations, or in a time period equal to the screening interval for women who have reached the upper age limit for screening.
implemented screening program, the prevalence screening will primarily occur in the youngest age groups. The next screening rounds are termed subsequent or incident screening rounds17.
1.2.3 Benefits and harms of mammography screening
The balance between benefits and harms of mammography screening has been debated for decades. Although the potential for side-effects of screening in general were discussed already in 1968 [53], the attention on such aspects in the specific situation of screening for breast cancer with mammography has increased over time [14, 54, 56]. The major harms of screening include overdiagnosis, false positive and false negative mammograms. Overdiagnosis18 of breast cancer in the context of a mammography screening program is defined as a breast cancer that would not be detected during the woman’s lifetime in the absence of the program. One of the major challenges with overdiagnosis is that is it not possible to identify overdiagnosed tumors at an individual level. When a cancer is diagnosed at screening, it is not possible to foresee whether that particular cancer would progress to cause symptoms during the woman’s remaining lifetime or not, since both the exact individual tumor progression and the woman’s remaining lifetime is unknown at the time of diagnosis. As a result, all breast cancers are treated as potentially lethal. For women with tumors that would never be detected without the screening program, this treatment would be unnecessary, and would increase both the human and monetary costs associated with screening. In addition, a cancer diagnosis in itself may have a substantial impact on quality of life, even without considering adverse effects of treatment. A certain amount of overdiagnosis is inevitable in a screening program that succeeds in advancing the time of diagnosis to a preclinical stage.
Women who are recalled for further examination due to abnormal mammograms, but who do not have breast cancer, will be subjected to the various diagnostic procedures without experiencing any personal benefit, in addition to the mental distress associated with the cancer suspicion inherent in an abnormal mammogram. Women with interval cancer may be considered as given a false sense of security by the screening program.
In the context of a publicly financed mammography screening program, the costs of the program must also be considered in light of the balance between benefits and harms. For an individual woman, awareness of both the chance of preventing death from breast cancer and the risk of unnecessary diagnostic procedures and treatment, are important aspects in the decision to attend or not to attend when invited for
mammography screening.
17Incident or subsequent screening refers to all screening rounds or screening examinations after the
prevalence screening.
18
Overdiagnosis due to mammography screening is the detection of breast cancer at screening that would not have caused symptoms during the woman’s lifetime, and thus would not have been detected without screening.