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 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 PO

Screen detected 267 148

Interval cancers 50 88

Incident cancers 305 374

Total 622 610 [Total in situ 71 16]

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

0

5

10

15

20

25

30

35

1950 1960 1970 1980 1990 2000

Year

Age standardized rates per 100,000

UKDenmarkNetherlandsCanadaUSASwedenFinland

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) 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 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 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 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

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

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

Numbercontacted

Attended PHC

Number abnormal

% diagnosed

Pilot – Area 1 4116 60% 291 82

Randomized year 2

1924 83% 63 83

Area 2 2264 91% 88 88

Re-screening 2254 73% 56 93

Area 3 2133 83% 114 78

Breast Cancer Detection (per 1,000)

Screen Control

Pilot 8.2 -

Randomized 3.5 3.1

Area 2 5.4 0.5

Re-screening 3.2 0.9

Area 3 5.1 3.1

Stage of detected cancers

Stage Pilot component Randomized component

All screened 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)

Screening Control

Number of women 75,360 76,178

Compliance 91%, 87%, 88%

Diagnosis compliance 68%, 71%, 78%

Breast cancers detected

32 24 25

Interval cancers 27 17 19 39 45

Total: early stage 78 38

advanced stage 47 49

Breast cancer deaths 22 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