Professor Martin Wiseman presented on 'The Continuous Update Project - Breast cancer survivors and prostate cancer' on behalf of WCRF International at the SCPN conference 04/02/2015.
The Continuous Update Project | Prof. Martin Wiseman
1. The Continuous Update Project
Breast cancer survivors
and prostate cancer
World Cancer Research Fund International, London UK
Professor Martin Wiseman FRCP FRCPath FAfN
NIHR BRC Southampton and University of Southampton
2. Who we are What we do
AICR (1982)
WCRF UK (1990)
WCRF Netherlands (1994)
WCRF Hong Kong (1997)
WCRF International (1999)
Fund research on the relationship of
nutrition, physical activity and body
weight to cancer risk
Interpret the accumulated scientific
literature to derive
Recommendations for Cancer
Prevention
Educate people through our national
Health Information programmes
Advocate effective policies to help
people and populations to reduce
their chances of developing cancer
6. 0
5
10
15
20
25
30
1960 1965 1970 -
'71
1973 -
'77
1979 -
'82
1983 -
'87
1988 -
'92
1995 1997
Colon
Breast
Cancer Incidence in Japan*
* Per 100,000, world population standard
CancerIncidence
8. Hanahan & Weinberg (2011) Cell; Hanahan & Coussens (2012) Cancer Cell
Hallmarks of cancer
Two enabling characteristics for acquiring hallmarks
10. WCRF/AICR EXPERT REPORT
The most authoritative
• New method
• Systematic reviews
• Review of evidence separate from
judgement
• Panel of international experts
• Predetermined criteria for judgements
– Epidemiology
– Mechanisms
• Flexibility
• Continuous update of evidence
12. NUTRITION AND CANCERS
• ADIPOSITY
– BREAST (PM), COLORECTUM, ENDOMETRIUM,
OESOPHAGUS, PANCREAS, GALLBLADDER, KIDNEY, OVARY,
PROSTATE (ADVANCED)
• PHYSICAL (IN)ACTIVITY
– COLON, BREAST
• MEAT – RED AND PROCESSED
– COLORECTAL
• ALCOHOL
– MPL, BREAST, COLORECTUM, LIVER
• PLANT FOODS (F&V, PULSES, WHOLEGRAINS)
– MPL, OESOPHAGUS, STOMACH, COLORECTAL (DF), LUNG
• BREASTFEEDING
– BREAST (MOTHER), OBESITY (CHILD)
13. The Panel emphasises the
importance of not smoking and of
avoiding exposure to tobacco smoke
14. USA UK BRAZIL CHINA
Mouth, pharynx,
larynx
63 67 63 44
Oesophagus 63 71 50 33
Lung 36 33 36 38
Stomach 47 45 41 33
Pancreas 19 15 11 8
Gallbladder 21 16 10 6
Liver 15 17 6 6
Colorectum 50 47 41 22
Breast 33 38 22 11
Ovary 5 4 3 1
Endometrium 59 44 37 21
Prostate (advanced) 11 10 5 4
Kidney 24 19 13 8
Total for these
cancers
30 32 25 24
Total for all cancers 21 24 17 20
Estimates of
cancer
preventability by
appropriate diet,
nutrition,
physical activity
and body fatness
18. Continuous Update Project: CUP
Same process for systematically
reviewing evidence for 2007 Report
Researchers at Imperial College London
– CUP database of epi research
– Systematically review the evidence
Expert Panel
– Draw conclusions
– Make recommendations
20. Grading criteria
Predefined requirements for
Number and types of studies
Quality of exposure and outcome assessment
Heterogeneity within and between study types
Exclusion of chance, bias or confounding
Biological gradient
Evidence of mechanisms
Size of effect
25. Prostate cancer – advanced
Advanced
– AJCC 1992 stage 3-4
– Advanced
– Advanced or metastatic
– Metastatic
– Whitmore/Jewett 3-4
– Fatal (prostate specific)
– High stage or grade
– Gleason 7 or more
33. Issues for prostate cancer
Heterogeneity of disease
Screen detected
Advanced or aggressive
Fatal
Characterisation of exposure
Lycopene
Calcium/dairy
35. Breast Cancer Survivors Included
Pre-menopausal women
Post-menopausal women
Incident in-situ breast cancer
Incident invasive breast cancer
36. Criteria for Study Inclusion
Randomised controlled trials
≥ 50 women
≥ 6 months follow-up
Only 2 identified (both low-fat diet trials)
Prospective cohort (follow-up) studies
Primary analysis, secondary analysis or
ancillary analysis of randomised controlled
trials, or follow-up studies in breast cancer
survivors
37. Exposures Included
Specific foods
Micro- and macro-nutrients
Dietary patterns
Alcohol
Overweight, obesity, underweight, weight
change, BMI
Body composition
Dietary supplements
Physical activity
38. Timing of Exposures
Pre-diagnosis
Within 12 months following diagnosis
Period of intensive primary therapy (surgery,
radiation, chemotherapy)
From 12 months after diagnosis
Patients may be receiving targeted therapy
during this period (e.g. hormonal therapy,
HER2neu, bone metastases prevention)
Data may extend 20 years or more
39. Outcomes Included
Total mortality
Breast cancer specific mortality
Second primary breast cancer
40. Outcomes Included
Total mortality
Breast cancer specific mortality
Second primary breast cancer
Not:
recurrence, QoL, lymphoedema etc
41. Literature search
(New search for CUP)
19831 unique records identified in Pubmed
and Embase until 30th June 2012 and 18
articles found in handsearch
897 full-text articles retrieved and
assessed for inclusion
319 articles on survival and health events
in women with breast cancer
18952 records excluded on the basis of
title and abstract
578 articles excluded for not fulfilling the
inclusion criteria
85 no original data
278 did not report on the associations
of interest
30 abstract/commentary
9 meta-analyses
94 irrelevant study design
33 follow-up less than 6 months
49 study smaller than 50 women
213 articles have mortality or any second
primary cancer as study endpoints
106 articles excluded on health events
other than death or second primary
cancer in women with breast cancer
45. Issues Relevant to
Survivor Research
Confounding effects of
Treatment types, efficacies, adverse effects
Stage of disease
Comorbidities
Type of cancer
Methodological
Determining cause of death
Screening for second primary breast cancer
Increasing length of survival
46. • Various associations also found for:
– Physical activity
– Foods containing fibre
– Foods containing soy
– Total fat
– Saturated fatty acids
• Evidence not judged strong enough to
conclude causal effects
49. Need for studies that control for
confounding by clinical variables
Randomised controlled trials
Cohort studies with accurate diagnostic &
treatment variables
Future Considerations
50. Summary
Although there were significant
associations between some exposures
and outcomes, incomplete adjustment for
potential confounders restricted the ability
to ascribe causality.
CUP Panel concluded that evidence is
limited.
51. CONCLUSIONS
• Nutrition (diet, body composition and physical
activity) is key determinant of global cancer patterns
• Evidence from epidemiology and mechanistic data
• CUP is refining knowledge of risk factors
– Heterogeneity of prostate cancer
– Body fatness and advanced prostate cancer
– Lycopene? Calcium/dairy?
– Body fatness and early life events are important for many
cancers
– Poor nutrition is an adverse diagnostic factor in breast
cancer – better studies needed to determine causality
54. Summary:
Before diagnosis- BMI
Total mortality
Breast cancer
mortality
Second primary
breast cancer
N
deaths
RR (95%CI)
N
deaths
RR (95%CI)
N
events
RR (95%CI)
High vs. Low 8318 1.41 (1.29-1.54) 9854 1.34 (1.23-1.46) 701 1.43 (0.87-2.34)
Underweight vs.
normal weight
4944 1.10 (0.92-1.31) 4479 1.02 (0.85-1.21) -
-
Per 5 kg/m2 6261 1.17 (1.13-1.21) 6600 1.17 (1.11-1.24) 701 1.21 (1.04-1.40)
Premenopause 644 1.25 (1.10-1.43) 1350 1.06 (0.85-1.32) -
-
Postmenopause 1103 1.16 (1.01-1.34) 2866 1.15 (1.05-1.25) -
-
55. Summary:
Around diagnosis- BMI
Total mortality
Breast cancer
mortality
Second primary
breast cancer
N
deaths
RR (95%CI)
N
deaths
RR (95%CI)
N
events
RR (95%CI)
High vs. Low
BMI
16925 1.27 (1.16-1.38) 10063 1.36 (1.23-1.50) 3478 1.30 (1.14-1.48)
Premenopause 4604 1.28 (1.16-1.42) 586 0.96 (0.45-2.06) -
-
Postmenopause 4614 1.13 (1.03-1.23) 1067 1.57 (1.31-1.89) -
-
Underweight vs.
normal weight
2598 1.23 (0.93-1.63) 1455 1.52 (1.26-1.84) -
-
Per 5 kg/m2 5875 1.11 (1.06-1.17) 1918 1.18 (1.11-1.25) 3186 1.13 (1.06-1.21)
56. Summary:
After diagnosis – BMI
Total mortality
Breast cancer
mortality
Second primary
breast cancer
N
deaths
RR (95%CI)
N
deaths
RR (95%CI)
N
events
RR (95%CI)
High vs. Low 2289 1.21 (1.06-1.38)
2 studies
Both risk, 1 significant
No studies
Underweight vs.
normal weight
1361 1.29 (1.02-1.63)
Per 5 kg/m2 1703
1.08 (1.01-1.15)
4, 0%, p=0.52
57. Summary: physical activity
Total mortality
Breast cancer
mortality
Events
RR (95%CI)
N, I2, P het
Events
RR (95%CI)
N, I2, P het
Before diagnosis
Total
H vs. L 505
0.83 (0.62-1.12)
2, 23%, p=0.25
338
0.80 (0.59-1.10)
2, 0%, p=0.88
Before diagnosis
Recreational
H vs. L 2892
0.74 (0.67-0.83)
8, 5%, p=0.39
1750
0.76 (0.61-0.95)
7, 49%, p=0.06
After diagnosis
Total H vs. L 514
0.63 (0.41-0.97)
3, 44%, p=0.16
217
0.81 (0.48-1.36)
2, 0%, p=0.63
Per 10 MET-
h/week
514
0.90 (0.79-1.03)
3, 79%, p=0.009
- -
After diagnosis
Recreational
H vs. L 2337
0.61 (0.50-0.74)
5, 46% ,p=12
392
0.71 (0.45-1.12)
2, 33%, p=0.22
After diagnosis
Recreational
Per 10 MET-
h/week
2337
0.81 (0.73-0.90)
5, 64%, p=0.03
- -
58. Summary: dietary fibre
Total mortality
Breast cancer
mortality
Events
RR (95%CI)
N, I2, P het
Events
RR (95%CI)
N, I2, P het
Before diagnosis H vs. L 417
0.50 (0.35-0.73)
2, 0%, p=0.83
2 studies
Non-sig risk
Per 10g/d 443
0.68 (0.55-0.84)
3, 0%, p=0.41
After diagnosis H vs. L 1092
0.76 (0.58-0.98)
3, 0%, p=0.99
332
0.82 (0.57-1.20)
3, 0%, p=0.95
Per 10g/d 1092
0.88 (0.78-0.99)
3, 0%, p=0.97
332
0.93 (0.80-1.07)
3, 0%, p=0.64
59. Summary: isoflavones
Total mortality
Events
RR (95%CI)
N, I2, P het
Before diagnosis H vs. L 624
0.87 (0.65-1.17)
3, 59%, p=0.06
After diagnosis H vs. L 794
0.70 (0.56-0.88)
3, 8%, p=0.33
Per 10mg/d 794
0.91 (0.83-1.00)
3, 68%, p=0.05
60. Summary: total fat
Total mortality
Breast cancer
mortality
Events
RR (95%CI)
N, I2, P het
Events
RR (95%CI)
N, I2, P het
Before diagnosis H vs. L (g/d) 655
1.87 (0.76-4.57)
3, 90%, p<0.001
521
1.13 (0.71-1.77)
4, 54%, p=0.09
Per 10g/d 178
1.19 (1.01-1.41)
4, 82%, p=0.001
- -
Per 10% energy 178
1.82 (1.41-2.36)
3, 0%, p=0.38
- -
After diagnosis H vs. L (g/d) 1436
1.08 (0.90-1.30)
3, 24%, p=0.27
648
1.19 (0.94-1.50)
4, 0%, p=0.41
Per 10g/d - -
575
1.01 (0.95-1.08)
3, 24%, p=0.27
61. After diagnosis: saturated fat
Outcome Author
Year
Study design Number of
events
Contrast RR
(95% CI)
Total
mortality
Beasley
2011
Follow-up of
cases from case-
control study
525 13% vs. 7%
energy
1.40 (1.06-1.87)
Total
mortality
Holmes
1999
Cancer survivors
of a cohort study
(NHS)
378 Q5 vs. Q1
g/d
1.23 (0.89-1.69)
Breast
cancer
mortality
Beasley
2011
Follow-up of
cases from case-
control study
137 13% vs. 7%
energy
1.55 (0.88-2.75)
Breast
cancer
mortality
Rohan
1993
Follow up of
cases from case-
control study
112 ≥45 vs <20g/d 1.65 (0.73-3.75)
For each of total mortality and breast cancer
mortality there were only two studies
62. Summary: Alcohol
Total mortality
Breast cancer
mortality
Second primary/
contralateral
breast cancer
N deaths RR (95%CI) N deaths RR (95%CI)
N
events
RR (95%CI)
Before
diagnosis:
High vs. Low
2650 0.93 (0.82-1.06) 1329 1.18 (0.81-1.72) - -
Before :
Per 1
drink/week
2676 1.00 (0.99-1.00) 1296 1.00 (0.97-1.02) -
-
After
diagnosis:
High vs. Low
3827
0.89 (0.72-1.09)
403 1.22 (0.88-1.69) 2347 1.19 (0.96-1.47)
After
diagnosis:
Per 10g/d
3779 0.98 (0.93-1.03) 403 1.06 (0.79-1.42) 2347 1.01 (0.99-1.03)