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Breast cancer 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 1st , 2nd, 3rd 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.

 

 
 

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