Early Detection: pros ad cons of different methodologies: education alone, BE/BSE, mammography

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Early Detection pros ad cons of different
methodologies education alone, BE/BSE,
mammography

• Anthony B. Miller
• Professor Emeritus, Dalla Lana School of Public
  Health, University of Toronto,
• Canada

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The problem

• In LMI countries, breast cancer is usually
  diagnosed at an advanced stage
• The majority of breast cancers are diagnosed in
  women under the age of 50
• Mammography screening is less effective in women
  under age 50, and the technical and personnel
  requirements for population-based mammography
  screening are very substantial.

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Early detection

• Public and professional education
• Professional education
• Breast self examination
• Clinical breast examination
• Mammography
• Adequate facilities for diagnosis

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IARC Working Group, 2002

• Reduction in risk of death from breast cancer by
  mammography screening
• Women aged 4049 12
• Women aged 5069 25

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The UK trial of mammography among women age 39-41

• 160,921 women randomised, 1 2, intervention
  control
• Mammography annually for 7 years in intervention
  arm
• 478 breast cancers diagnosed in intervention arm
  (8 excess), 809 in control

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The UK trial of mammography among women age 39-41

• Ratio of breast cancer deaths at mean follow-up
  of 10.7 years in intervention arm relative to the
  control
• 0.83 (95 CI 0.66-1.04)

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IARC Working Group, 2002

• There is inadequate evidence for the efficacy of
  screening women by clinical breast examination in
  reducing mortality from breast cancer.
• There is inadequate evidence for the efficacy of
  screening women by breast self-examination in
  reducing mortality from breast cancer.

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Canadian National Breast Screening Study (CNBSS)-2

• 39,405 women age 50-59 randomized to
• Annual two-view mammography physical
  examination (CBE) BSE (MP)
• Annual physical examination (CBE) BSE only (PO)
• 5 or 4 screens and 11-16 years follow-up

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Occurrence of Invasive Breast Cancers in CNBSS-2

• MP PO
• Screen detected 267 148
• Interval cancers 50 88
• Incident cancers 305 374
• Total 622 610
• Total in situ 71 16

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CNBSS-2 Deaths from breast cancer, 11-16 years
follow-up

• MP PO
• Women years (103) 216 216
• Breast cancer deaths 107 105
• Rate/10,000 4.95 4.86
• Rate ratio (95 CI) 1.02 (0.78, 1.33)

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Model based analysis of CNBSS 2 (Rijnsberger et
al, 2005)

• Mammography resulted in a 16-36 reduction in
  breast cancer mortality
• The breast examinations resulted in a 20
  reduction in breast cancer mortality, in
  comparison to no screening.

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Costeffectiveness of Screening in India (Okonkwo
et al, 2008)

• Programme Cost, per Yr Life saved
• Biennial CBE 1341
• age 40-60
• Biennial mammography 3468
• Age 40-60

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Explanations for trends

• Timing of recent fall compatible with
  improvements in therapy
• Timing and lack of effect in some countries is
  not compatible with an effect of mammography
  screening
• Lack of fall prior to 1990 suggests that early
  detection is not effective in the absence of
  effective treatment

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WHOs Recommendations

• Evaluate importance of breast cancer
• Evaluate available resources
• Ensure availability of Early diagnosis
• Ensure availability of therapy
• Introduce early detection based upon evidence
• If insufficient evidence-base, introduce
  screening as demonstration project first

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Cairo Breast Screening Trial

• Principal investigator Dr Salwa Boulos
• Statistician Dr Moysen Gadallah
• Senior Surgeon Dr Sherif Neguib
• Oncologist Dr A Youssef
• Pathologist Dr EA Essam
• Consultants A Costa, N Mittra, AB Miller
• Funding The Challenge Fund

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Principal Objectives of the trial

• To determine whether breast examinations
• combined with the teaching of breast
  self-examination (CBEBSE), performed once a
  year by trained health professionals, reduces the
  cumulative incidence of advanced (stage 3 or
  worse) breast cancer.
• 2. To determine whether CBEBSE reduces mortality
  from breast cancer.

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Criteria of Eligibility

• Women age 40-64
• No personal history of breast cancer,
• Resident in the study area,
• Not enrolled in any other breast screening
  program
• Consent has been obtained

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Reasons for starting at age 40

• The incidence of breast cancer is lower in women
  age 35-39 than 40-44
• More women age 35-39 have to be examined to find
  a case of breast cancer than women age 40-44
• The costs will be lower, and the screening tests
  more productive, if we restrict the age range

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Breast cancer incidence rates (per 100,000)

• Age Canada Egypt Casablanca
• 35-39 51.8 63.6 50.3
• 40-44 107.6 96.7 95.1
• 45-49 162.9 144.9 109.1
• 50-54 199.4 171.5 107.2
• 55-59 229.0 181.2 116.8
• 60-64 285.5 144.2 96.7

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Number of women to be examined, to find one case
of breast cancer

• Age Canada Egypt Casablanca
• 35-39 1930 1572 1988
• 40-44 929 1034 1051
• 45-49 614 690 917
• 50-54 502 583 933
• 55-59 437 552 856
• 60-64 350 693 1034

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Recruitment and registration

• Areas were identified with easy access to the
  designated breast diagnosis centre. These
  contained the homes of over 10,000 women, of whom
  about 5,000 were the target age group (40-64).
• Visits were performed by trained social workers
  to these homes in a systematic manner, aided by
  maps.

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Recruitment and registration -2

• All women age 40-64 identified were registered,
  their ID information recorded, and interviewed
  using a breast cancer risk factor questionnaire.
• Health information on breast cancer was provided,
  and they were told where to attend if they have a
  problem with their breasts.

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Randomisation (after Pilot study)

• Group (cluster) - defined by sub-area (social
  worker).
• All women in designated sub-areas were invited to
  attend the designated primary health centre,
  staffed by young female doctors, carefully
  trained in CBEBSE.

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Process for screening

• CBE performed and BSE taught
• Those deemed abnormal referred to the diagnosis
  centre
• At diagnosis centre, women re-examined by study
  surgeon
• Those confirmed abnormal receive mammography, and
  if needed ultrasound and FNA

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Results

• Population compliance at PHC for screening
• Pilot study (initial) 60
• Group A 83
• Area 2 91
• Re-screening 73
• Area 3 83

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Results - 2

• Number found with abnormalities (percent attended
  for diagnosis)
• Pilot study 291 (82)
• Group A 63 (83)
• Area 2 88 (88)
• Rescreening 56 (93)
• Area 3 114 (78)

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Results - 3

• Breast cancer detection CBE screening
• Pilot study 8 per 1,000
• Re-screening 2 per 1,000
• Area 2 6 per 1,000
• Re-screening 3 per 1,000
• Area 3 5 per 1,000

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Preliminary results on staging

• Screen Control
• Stage 1 30 8
• Stage II 43 18
• Stage III 20 44
• Stage IV 7 30
• 5 cases were detected in the prevalence round

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Conclusions

• The approach is feasible, and is being replicated
  in other centres Sanaa, Khartoum, Yazd
• The projects are providing evidence that earlier
  stage at diagnosis can be achieved by CBE
  screening
• Other EMRO countries should consider such
  projects as an alternative to mammography
  screening