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 population- based 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 of asymptomatic women

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

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

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

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 )

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 n 39,405 women age 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 years follow-up

Occurrence of Invasive Breast Cancers in CNBSS-2 MP PO Screen detected Interval cancers Incident cancers Total [Total in situ 71 16]

CNBSS-2 Deaths from breast cancer, years follow-up MPPO Women years (10 3 ) Breast cancer deaths Rate/10, 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.

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 nurses trained  BSE taught  CBE offered Breast cancers presenting at late stage (III & IV) u 77% in 1993 u 37% in 1998

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.

Criteria of Eligibility  Women age  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 than  More women age have to be examined to find a case of breast cancer than women age 40-44

Breast cancer incidence rates (per 100,000) Age CanadaEgypt Casablanca

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

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 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 %29182 Randomized year %6383 Area %88 Re-screening %5693 Area %11478

Breast Cancer Detection (per 1,000) ScreenControl Pilot8.2- Randomized Area Re-screening Area

Stage of detected cancers StagePilot componentRandomized component All screenedScreenedControl NumberPercentNumberPercentNumberPercent I II III IV Total

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 Interval cancers Total: early stage7838 advanced stage4749 Breast cancer deaths2210

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