This current thesis is based on information collected by the Finnish National Breast Cancer Screening Programme (FNBCSP). The target population in the sub-studies were women aged 50-69 and invited for screening mammography. Studies I and II used data provided by the Mass Screening Registry (MSR) and the Finnish Cancer Registry (FCR). In addition to these, study III used Central Population Registry (CPR) data and study IV used CPR and Statistics Finland data. (Table 2)
The first sub-study (I) was a cross-sectional study conducted in women who attended screening mammography between 2006 and 2010. Altogether, 1,198,410 screening visits were studied (Table 3). The second study (II) was a historical cohort study conducted in women invited to screening mammography for the first time at ages 50-51 between 1992 and 2004 and who were followed up with until 2012. In total, 2,189,800 visits with and without symptoms were studied.
The matched cohort studies (III and IV) were conducted in women who attended screening mammography between 1992 and 2012. The exposure group (visits in women with breast symptoms at a given screening visit) and reference group (visits in women with no breast symptoms in the screening history before the index visit) were selected independently of the symptom status. Here, the index visit meant any screening visit with any given symptom and a respective asymptomatic visit was selected for every symptomatic visit based on the matching criteria. Altogether, 198,622 visits were analysed in study III and 151,956 visits were analysed in study IV.
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Table 3. Study design, main method and variables by the sub-studies
Study I Study II Study III Study IV
Study design Cross-sectional study Historical cohort study Matched cohort study Matched cohort study Main statistical method Logistic regression Discrete-time hazard regression Cox-proportional hazards
model
Cox-proportional hazards model Main independent
variables
Lump Lump Lump Lump
Retraction Retraction Retraction Retraction
Secretion Nipple discharge Nipple discharge Nipple discharge
Scar Mole
Performance indicators Attendance proportion False-positive test proportion First and subsequent round attendance proportion
First and subsequent round attendance proportion
Recall proportion False-positive referral proportion
Referral proportion True-positive proportion Positive predictive value Duration between symptoms and cancer diagnosis
Positive predictive value Test sensitivity
Sensitivity Episode sensitivity Duration between
symptoms and mortality
Specificity Specificity
Cancer detection rate Negative predictive value
Main outcome variables Screen-detected cancers False-positive tests Screen-detected cancers Screen-detected cancers Tumour characteristics (TNM
classification)
False-positive referrals Interval cancers All cause death
True-positive referrals Deaths due to breast cancer Deaths due to breast cancer
Table 4. Definitions used for the study variables required for the performance indicators
Serial number Variables Definition
1. Test positive Screening visit with primary mammography positive (recalled for further assessment or diagnostics)
2. Test negative Screening visits with negative/normal mammography (i.e. not recalled for further assessment nor diagnostics)
3. False-positive test Screening visit with positive mammography but negative further assessment or histological confirmation (i.e. no breast cancer)
4. False-positive referral Screening visit with positive mammography and referral for biopsy/surgery, but negative histological confirmation (i.e. no breast cancer diagnosed)
5. Episode negative Screening visit with negative mammography (no recall), or positive mammography but negative further assessment or negative histological confirmation
6. True positive Screening visit with positive mammography and screen-detected breast cancer
diagnosed in the same visit
7. Screen-detected cancer Primary breast cancer diagnosed within 6 months following a positive mammography 8. Interval cancer Breast cancer diagnosed in a screened woman before the next screening visit or within
a period equal to a screening interval after: a negative mammography; a positive mammography but negative further assessment (recall negative); positive further assessment but date of diagnosis more than 6 months after screening mammography
9. Subsequent round screen-detected
cancer
A primary breast cancer diagnosed at the subsequent screening visit in a screen negative woman at the index visit
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Table 5. Definitions of the performance and outcome indicators
Serial number Variables Definition
1. Breast cancer detection rate (Study I) The number of cancer cases detected at screen divided by number of screening visits expressed in 1000 or 10000
2. Sensitivity of a symptom (Study I) Number of visits with a symptom with malignant cancers, divided by the total number of visits with breast cancer
3. Positive predictive value (PPV) (Study I) Number of visits with cancer diagnosed in those who had symptoms
4. Test sensitivity (mammography) Number of visits with screen detected cancers divided by the sum of screen-detected cancers plus interval cancers diagnosed after negative test results (detection method) (Hakama, Pokhrel et al. 2015)
5. Episode sensitivity Number of visits with breast cancer detected in the full diagnostic process divided by all cancers detected over a screening round among attenders
6. Positive predictive value of
mammography (PPV)
Number of visits with a positive mammography test and diagnosis of cancer divided by the number of all test positives
7. Negative predictive value of
mammography (NPV)
Number of visits with a negative mammography test and no cancer diagnosed divided by the number of all test negatives
8. Specificity of mammography Number of visits with a negative mammography test and no cancer diagnosed divided by the number of all visits with no cancer diagnosed
9. Breast cancer incidence New breast cancers diagnosedafter the first invitation by the programme divided by the person-years at risk
Incidence of fatal breast cancers (Study III): A subcategory of breast cancer incidence was formed of those breast cancers from which the women died. Follow up closed at the time of cancer incidence
10. Breast cancer mortality Deaths due to breast cancer diagnosed after the first invitation by the programme divided by person-years at risk. Follow up closed at the time of death
11. All-cause mortality Deaths due to any cause, including breast cancer deaths after the first invitation in the programme divided by person-years at risk
The above tables, 4 and 5 illustrates the definition of variables used in the studies. The variables are defined in the context of the mammography programme performance and the output indicators. In study I, we calculated the clinical validity parameters of symptoms within a screening episode whereas, in study II and study III we analyzed the performance measures of mammography in relation to symptoms in a screening round. Thus, the definition of parameters such as sensitivity, PPV, NPV differ between the studies.