Transcript Early Detection of breast cancer

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