1. Early Detection of breast cancer Anthony B. Miller, MD, FRCP Associate Director, Research, Dalla Lana School of Public Health, University of Toronto, Canada

2. The problem  In low and middle income 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.

3. Early detection  Public education  Professional education  Breast self examination  Clinical breast examination  Mammography

4. Two linked broad strategies  Early diagnosis of symptomatic women  Screening of asymptomatic women

5. Prerequisites for both strategies  Adequate facilities for diagnosis  Effective, accessible, affordable, treatment

6. Requirements for effective screening  An informed decision to initiate or re- organize screening in the context of a National Cancer Control Programme  The political will to proceed  Support and funding from the Ministry of Health  An adequate health care infrastructure  Trained and informed managers

7. IARC Working Group, 2002 Reduction in risk of death from breast cancer by mammography screening:  Women aged 40–49: 12%  Women aged 50–69: 25%

8. The UK trial of mammography among women age 39-41  160,921 women randomized, 1: 2, intervention : control  Mammography annually for 7 years in intervention arm  All women enter UK screening program at age 50

9. 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)

10. Review for US Preventive Services Task Force (Nelson et al, 2009) Relative risk of breast cancer death, mammography vs. no screening, for women age 40-49: 0.85 (95% CI 0.75-0.96)

11. 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.

12. Canadian National Breast Screening Study (CNBSS)-2 n 39,405 women age 50-59 randomized to: u Annual two-view mammography + physical examination (CBE) + BSE (MP) u Annual physical examination (CBE) + BSE only (PO) n 5 or 4 screens and 11-16 years follow-up

13. Occurrence of Invasive Breast Cancers in CNBSS-2 MP PO Screen detected267 148 Interval cancers 50 88 Incident cancers305374 Total622610 [Total in situ 71 16]

14. CNBSS-2 Deaths from breast cancer, 11-16 years follow-up MPPO Women years (10 3 )216 216 Breast cancer deaths 107 105 Rate/10,000 4.95 4.86 Rate ratio (95% CI) 1.02 (0.78, 1.33)

15. Model based analysis of CNBSS 2 (Rijnsberger et al, 2005) In comparison to no screening, as in the control group of the Swedish Two-county trial, the breast examinations resulted in a 20% reduction in breast cancer mortality.

17. 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

18. Community program in Sarawak, Malaysia (Devi et al, 2007)  Community nurses trained  BSE taught  CBE offered Breast cancers presenting at late stage (III & IV) u 77% in 1993 u 37% in 1998

19. The Cairo Breast Screening Trial (Boulos et al, 2005) 1.To determine whether breast examinations combined with the teaching of breast self- examination (CBE+BSE), performed by trained health professionals, reduces the cumulative incidence of advanced (stage 3 or worse) breast cancer. 2.To determine whether CBE+BSE reduces mortality from breast cancer.

20. 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

21. 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

22. Breast cancer incidence rates (per 100,000) Age CanadaEgypt Casablanca 35-39 51.8 63.650.3 40-44 107.6 96.795.1 45-49 162.9144.9 109.1 50-54 199.4171.5 107.2 55-59 229.0181.2 116.8 60-64 285.5 144.296.7

23. Number of women to be examined, to find one case of breast cancer Age CanadaEgypt 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

24. Recruitment and registration Areas were identified with easy access to the designated breast diagnosis centre. Visits were performed by trained social workers to every home in a systematic manner, aided by maps. Women age 40-64 were identified and interviewed using a breast cancer risk factor questionnaire. Health information on breast cancer was provided. They were told where to attend if they have a problem with their breasts.

25. Randomisation (after Pilot study) Group (cluster) - defined by sub-area (social worker). All women randomized to screening were invited to attend the designated primary health centre, staffed by young female doctors, carefully trained in CBE+BSE.

26. Process for screening and diagnosis CBE performed and BSE taught at PHC 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

27. Compliance, screened group Number contacted Attended PHC Number abnormal % diagnosed Pilot – Area 1 411660%29182 Randomized year 2 192483%6383 Area 2 226491%88 Re-screening 225473%5693 Area 3 213383%11478

28. Breast Cancer Detection (per 1,000) ScreenControl Pilot8.2- Randomized3.53.1 Area 25.40.5 Re-screening3.20.9 Area 35.13.1

29. Stage of detected cancers StagePilot componentRandomized component All screenedScreenedControl NumberPercentNumberPercentNumberPercent I531930212 II9561137425 III16827744 IV1627319 Total16993010116100

30. The Mumbai Breast Screening Trial (Mittra et al, 2009) ScreeningControl Number of women75,36076,178 Compliance91%, 87%, 88% Diagnosis compliance68%, 71%, 78% Breast cancers detected 32 24 25 Interval cancers 27 1719 39 45 Total: early stage7838 advanced stage4749 Breast cancer deaths2210

31. Conclusions  Mammography screening may not be superior to early diagnosis plus adequate treatment  Alternative approaches to screening are being evaluated in a number of LMIC settings  We are beginning to collect good data on effectiveness  Such research should continue and be expanded