Breast screening

Criteria for an effective screening programme

The disease screened for must be an important problem.
The natural history of the disease should be well understood with a recognisable early stage.
A specific and sensitive test for the early detection of the disease must be available.
There should be good evidence that the screening test can result in reduced mortality and morbidity in the targeted population.
The test must be acceptable producing a high participation rate.
There should be suitable facilities for diagnosis and treatment of detected abnormalities.
There should be appropriate treatment options.
The benefits of screening should outweigh any adverse effects.
The benefit must be of an acceptable financial cost.
The results of the implementation require audit to ensure they meet the above criteria.

Sensitivity and specificity

A screening test can give a positive or negative result
Does not imply that the patient has or does not have the disease
The test results can be:
- True positive (TP) = A positive test result in the presence of the disease
- True negative (TN) = A negative test result in the absence of the disease
- False positive (FP) = A positive test result in the absence of the disease
- False negative (FN) = A negative test result in the presence of the disease
Sensitivity = the ability of the test to identify the disease in those who have it
- Equals TP / (TP + FN)
Specificity = the ability of the test to exclude the disease in the absence of the disease
- Equals TN / (TN + FP)

Ductal carcinoma in-situ

DCIS is non-invasive breast carcinoma
Malignant cells remain within the basement membrane
True DCIS does not cause lymph node metastases
Not all cases progress to invasive cancer
Usually asymptomatic
Was rarely identified prior to the establishment of breast screening
Usually presents as malignant microcalcification on screening mammography
Often multifocal disease process
Management depends on:
- Extent of lesion
- Nuclear grade

Is breast cancer screening worthwhile ?

An important problem
- Single leading cause of cancer death in women
- Lifetime incidence is approximately 1:12
The natural history - many unanswered questions
- Does ductal carcinoma in-situ (DCIS) always proceed to invasive cancer ?
- At what stage does invasive cancer cease to be localised to the breast?
- At what interval does screening need to be repeated?
A suitable test
- Single view mammography is 90% sensitive and 95-99% specific
- Breast examination adds nothing to value of mammographic screening
Screening is effective
- Primary aim of screening is the reduction of breast cancer mortality -proven
- Best evidence comes from randomised control trials
Avoid screening biases:
- Selection Bias - patients select themselves into one group by attending
- Lead Time Bias - Early detection appears to improve survival by increasing time form diagnosis to death yet mortality is unchanged. The patient is simply aware that she has the disease for longer
- Length Bias - Slower growing better prognosis tumours are more likely to be detected by screening
An acceptable test
- If screening test is acceptable the compliance will be increased and mortality reduced
- Compliance of >70% will impact on mortality
- Compliance decreases with age
Facilities for diagnosis and treatment
- Need facilities for radiology, clinical assessment, cytology, surgery, pathology etc.
- Appropriate treatment options
- Treatment must impact on natural course of disease
- Must have tolerable and minimal side effects
Adverse effects and cost-benefit analysis
- Resources required
- Exposure of women to ionising radiation
- False positive results with unnecessary biopsies
- Unnecessary treatment of lesions that may never have caused problems

History of breast screening

Health Insurance Plan of New York (HIP) Study

Began in 1963,
Randomised control trial of 60,000 women
67% accepted invitation for two view mammography and clinical examination
Followed up with yearly mammography and examination
Controls received routine medical care
Mammography alone detected 30% of breast cancers
Clinical examination detected a further 45%
At 10 years mortality from cancer detected in first 5 years was reduced by 30%
Largest effect in women > 50 years

Breast Cancer Detection Demonstration Project (BCDDP)

Began in 1973
Designed to test conduct of screening rather than efficacy of screening
280,000 women between 35 & 74 years enrolled
5 yearly mammography and clinical examination
No control group. Compared with HIP data
Screening effective for women > 40 years
Effect particularly good for cancers detected by screening only

Swedish two county trial

Began in 1977
Randomised control trial of mass screening
135,000 women between 40 & 74 years
Two area compared. Kopparberg and Ostergotland
Single mediolateral oblique view mammography
High compliance rates - 89% at prevalence round and 83% at incidence round
13% of control group underwent mammography as part of normal medical care
By 1984 31% reduction in breast cancer mortality was seen in screened group
Effect greatest in women >50 years

Netherlands case control studies

Cases = Deaths from breast cancer after first screening round
Controls = Random sample of age matched women alive at time of case death
Odds ratio for breast cancer deaths calculated
Women self selected into screened and non-screened group
Selection bias possible
Non screened population of Arnhem used to provide control breast cancer rates and to estimate effect of selection bias in Nijmegen population

Nijmegen Project

Began in 1975
Single view mammography every 2 years
23 000 women between 35 & 65 invited for screening
52% reduction in breast cancer mortality in screened group

DOM Project

Began in 1974
Clinical examination and mammography at 12, 18 and 24 months
20,500 women between 50 & 64 years

Conclusions from initial breast screening trials

Every major trail shows that screening reduced risk of death from breast cancer in women > 50 years
Effect begins 5-7 years after screening has commenced
Mortality curves were diverging at time of analysis and likely to increase in significance with time
For women < 50 years no trial has shown a reduction in mortality from screening

National Heath Service Breast Screening Programme

Introduced in 1988 with 95 screening programmes
Followed Forest Report (1986)
All women 50-64 years invited for 3 yearly single view mammography
Upper age limit soon to be extended to 70 years
If abnormality seen on mammogram women are recalled for:
- Clinical examination
- Further imaging - mammography or ultrasound
- Fine needle aspiration cytology or core biopsy
70% of screen detected abnormalities shown to be unimportant following triple assessment

Current controversies in breast screening

Number of mammographic views
- UKCCR multicentre randomised control trial of one and two view mammography
- Two view mammography detects 24% more cancers and leads to recall of 15% fewer women
- Most centres now perform 2 view mammography at first screening
- Two views will soon be performed at all screening rounds
Frequency of screening
- Concern that 3 yearly screening interval too long
- Most European countries screen every 2 years
- Interval cancers = cancers occurring between screening episodes
- Rates in 1^st , 2^nd, 3^rd year after screening 24%, 59% and 79% expected incidence in the absence of screening
- Currently no evidence to suggest that more frequent screening reduces breast cancer mortality
Screening under 50 years of age
- Only 20% breast cancers occur in women less than 50 years
- Meta-analysis of all available trial results suggest non significant reduction in mortality
- Sensitivity of mammography reduced in the young breast

Bibliography

Alexander F E, Anderson T J, Brown H K et al. 14 years of follow-up from the Edinburgh randomised trial of breast screening. Lancet 1999; 355: 1903-1908.

Dixon J M, Ravischer O, Cunningham M et al. Factors affecting outcome of patients with impalpable breast cancer detected by breast screening. Br J Surg 1996; 83: 997-1001.

Gilbert F J. Screening for breast cancer. Br J Hosp Med 1997; 58: 595-598.

Gotzsche P, Olson O. Is screening for breast cancer with mammography justifiable? Lancet 2000; 355: 12-134.

Miller A B, To T, Baines C J, Wall C. The Canadian National Breast Screening Study-1: breast cancer mortality after 11-16 years of follow up. Ann Intern Med 2002; 137: 305-312.

Rickard M T. Current issues in mammographic breast cancer screening. Hosp Med 1999; 60: 325-328.

Smart C R, Hendrick R E, Rutledge J H et al. Benefits of mammography screening in women aged 40-49. Cancer 1995; 75: 1619 –1626.

The Breast Screening Frequency Trial Group. The frequency of breast cancer screening: results from the UKCCR randomised trial. Eur J Cancer 2002; 38: 1458-1464.

Wald N J, Murphy P, Major P et al. UKCCR multicentre randomised controlled trail of one and two view mammography in breast cancer screening. Br Med J 1995; 311: 1189-1194

Woodman C B, Threlfall A G, Boggis C R et al. Is the three year breast screening interval too long? Occurrence of interval cancers in the NHS breast screening programmes north western region. Br Med J 1995; 310: 224-2.

Breast cancer screening