Under- and Overdiagnosis in BreastScreen Norway

Study Overview
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Brief Summary
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This PhD project will describe tumour characteristics and survival associated with of under- and overdiagnosed breast cancers, the rate of overdiagnosis in BreastScreen Norway, and whether women and family doctors are aware of, and knowledgeable about, under- and overdiagnosis in breast cancer screening.

Detailed Description
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Mammographic screening among women aged 50-69 reduces breast cancer mortality but also carries some risk. This PhD project will study under- and overdiagnosis, two risks associated with mammographic screening, in BreastScreen Norway. Underdiagnosis can occur when a tumour is present but not detected as a result of screening, while overdiagnosis can occur when a woman is diagnosed with a slow growing cancer that would not become symptomatic during her lifetime. This project will address the following topics and research questions using observational study methods. Study 1: To determine whether tumour histopathology and survival differentially associated with potentially under- or overdiagnosed interval and screen-detected breast cancers. Do women with potentially underdiagnosed interval cancers have different tumour histopathology and survival than those whose interval cancers showed no signs at the prior screen? Do women with potentially overdiagnosed screen-detected cancer have different tumour histopathology and survival than those whose screen-detected cancer showed no signs at the prior screen? Study 2: To estimate overdiagnosis in the screening program using individual-level data: What was the rate of overdiagnosis for women screened in the program during 1996-2003? How does adjusting for sociodemographic factors affect estimates of overdiagnosis? Study 3: To describe awareness and knowledge about under- and overdiagnosis and breast screening in general: Are women aware of and knowledgeable about under- and overdiagnosis in breast screening? Are family doctors aware of and knowledgeable about breast screening, and under- and overdiagnosis? Are they confident in their ability to relay this information to their patients? Study 1 is a quality improvement study and has approval from Personvernombudet (PVO 2016-4696). Study 2 has research ethics board (REK) approval (REK 2013/795), while REK approval will be sought for Study 3.

Official Title
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Under- and Overdiagnosis in BreastScreen Norway

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Under- or overdiagnosed cancer
* Other: Screening


Participation Criteria
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Eligibility Criteria
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Study 1 Inclusion Criteria: Breast cancer diagnosed within BreastScreen Norway using digital mammography Prior screening images available for review Study 2 Inclusion Criteria: Women born between 1927 and 1934 (inclusive) Legal resident in Norway at any time between 1996 and 2003 (inclusive) Study 3 Inclusion Criteria: Women residing in Norway, aged 50-69 (inclusive) Practising family doctors in Norway, aged 25-75 (inclusive) Provide informed consent

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study 1: Under- and overdiagnosed group<br>Non-proportional stratified sample of women diagnosed with interval or screen-detected breast cancers after participation in BreastScreen Norway. This sample will include under- or overdiagnosed cancers, as well as cancers that were not under- or overdiagnosed. | Other: Under- or overdiagnosed cancer<br>* Diagnosed with a cancer that was visible on prior mammograms<br>|
| Study 2: Rate of overdiagnosis group<br>Women residing in Norway, born between 1927 and 1934 (inclusive). This cohort will include women who have attended screening and who have not attended screening. | Other: Screening<br>* Invited or attended BreastScreen Norway<br>|
| Study 3: Awareness and knowledge group<br>Women aged 50-69, and practising family doctors aged 25-75, currently living in Norway. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Prognostic and predictive histopathologic characteristics | - Histopathological type (Ductal carcinoma in situ, invasive carcinoma of no special type, invasive lobular carcinoma) | At time of diagnosis | 
| Study 1: Prognostic and predictive histopathologic characteristics | - Maximum tumour diameter (mm) | At time of diagnosis | 
| Study 1: Prognostic and predictive histopathologic characteristics | - Tumour grade (1, 2, 3) | At time of diagnosis | 
| Study 1: Prognostic and predictive histopathologic characteristics | - Lymph node involvement (Yes/No) | At time of diagnosis | 
| Study 1: Prognostic and predictive histopathologic characteristics | - Receptor status (Positive/Negative) | At time of diagnosis | 
| Study 1: Prognostic and predictive histopathologic characteristics | - Ki67 expression (0-100%) | At time of diagnosis | 
| Study 2: Crude and adjusted rate of overdiagnosis | - Crude and adjusted measures of overdiagnosis will be presented to show the amount and direction of confounding resulting from sociodemographic factors. | 1996 to 2016 | 
| Study 3: Agreement between awareness and knowledge of overdiagnosis | Agreement between awareness (yes versus no/incomplete) and knowledge (yes versus no/incomplete) of overdiagnosis | One day (Measurements taken once at time of survey completion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Survival | - Overall survival | Date of diagnosis until 31 December 2017 | 
| Study 1: Survival | - Breast cancer specific survival | Date of diagnosis until 31 December 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Screening, Mammography, Overdiagnosis, Womens' perspectives, Harms and benefits, False negative, Quantitative methods, Survival