Early Detection of breast cancer Anthony B. Miller, MD, FRCP Associate Director, Research, Dalla Lana School of Public Health, University of Toronto, Canada 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 populationbased mammography screening are very substantial. Early detection Public education Professional education Breast self examination Clinical breast examination Mammography Two linked broad strategies Early diagnosis of symptomatic women Screening women of asymptomatic Prerequisites for both strategies Adequate facilities for diagnosis Effective, accessible, affordable, treatment Requirements for effective screening An informed decision to initiate or reorganize 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 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% 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 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) 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) 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. 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 Occurrence of Invasive Breast Cancers in CNBSS-2 MP Screen detected 267 Interval cancers 50 Incident cancers 305 Total 622 PO 148 88 374 610 [Total in situ 16] 71 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) 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. Trends in Mortality from Breast Cancer Age standardized rates per 100,000 35 30 UK Denmark Netherlands Canada USA Sweden Finland 25 20 15 10 5 0 1950 1960 1970 1980 Year 1990 2000 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 Community program in Sarawak, Malaysia (Devi et al, 2007) Community BSE nurses trained taught CBE offered Breast cancers presenting at late stage (III & IV) 77% in 1993 37% in 1998 The Cairo Breast Screening Trial (Boulos et al, 2005) 1. To determine whether breast examinations combined with the teaching of breast selfexamination (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. 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 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 Breast cancer incidence rates (per 100,000) Age 35-39 40-44 45-49 50-54 55-59 60-64 Canada 51.8 107.6 162.9 199.4 229.0 285.5 Egypt 63.6 96.7 144.9 171.5 181.2 144.2 Casablanca 50.3 95.1 109.1 107.2 116.8 96.7 Number of women to be examined, to find one case of breast cancer Age 35-39 40-44 45-49 50-54 55-59 60-64 Canada 1930 929 614 502 437 350 Egypt 1572 1034 690 583 552 693 Casablanca 1988 1051 917 933 856 1034 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. 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. 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 Compliance, screened group Number contacted Attended PHC Number abnormal % diagnosed Pilot – Area 1 4116 60% 291 82 Randomized year 2 Area 2 1924 83% 63 83 2264 91% 88 88 Re-screening 2254 73% 56 93 Area 3 2133 83% 114 78 Breast Cancer Detection (per 1,000) Pilot Randomized Area 2 Re-screening Area 3 Screen Control 8.2 - 3.5 3.1 5.4 0.5 3.2 0.9 5.1 3.1 Stage of detected cancers Stage Pilot component All screened Randomized component Screened Control Number Percent Number Percent Number Percent I 5 31 9 30 2 12 II 9 56 11 37 4 25 III 1 6 8 27 7 44 IV 1 6 2 7 3 19 Total 16 99 30 101 16 100 The Mumbai Breast Screening Trial (Mittra et al, 2009) Number of women Screening Control 75,360 76,178 Compliance 91%, 87%, 88% Diagnosis compliance Breast cancers detected Interval cancers 68%, 71%, 78% 32 24 25 Total: early stage advanced stage Breast cancer deaths 78 47 22 27 17 19 39 45 38 49 10 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