breast cancer survivors report (conference: diet and cancer: from prevention to survival 1-3 october...
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Diet and breast cancer survival: results of the Continuous Update Project (CUP). Presentation given by Teresa Norat, Principal Investigator Continuous Update Project, Imperial College London.TRANSCRIPT
Teresa Norat
Principal Investigator Continuous Update Project, Imperial College London
Diet and breast cancer survival: results of the Continuous Update Project
‘Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective’
Not possible to draw firm conclusions that apply to cancer survivors specifically
Evidence was emerging but not sufficiently developed
Panel concluded cancer survivors should aim to follow the recommendations for prevention of cancer
Second Expert Report (2007)
Continuous Update Project Protocol
Breast Cancer Survivors Populations
In cancer, a person is considered to be a survivor from the time of diagnosis until the end of life
Pre-menopausal women Post-menopausal women Incident in-situ breast cancer Incident invasive breast cancer
Specific foods Micro- and macro-nutrients Dietary patterns Alcohol Overweight, obesity, underweight, weight
change Body composition Dietary supplements Physical activity
Continuous Update Project Protocol
Breast Cancer Survivors Exposure/interventions
Timing of Exposures Included
Pre-diagnosis Immediate 12 months following diagnosis
Period of intensive primary therapy (surgery, radiation, chemotherapy)
After 12 months post-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
Total mortality Breast cancer specific mortality Second primary breast cancer Other cause-specific mortality, i.e.
cardiovascular
Continuous Update Project Protocol
Breast Cancer Survivors Outcomes
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 randomized controlled trials, or follow-up studies in breast cancer survivors
Continuous Update Project Protocol
Breast Cancer Survivors Study designs
Literature search(New search for Continuous Update Project )
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 data278 did not report on the associations of interest30 abstract/commentary9 meta-analyses94 irrelevant study design33 follow-up less than 6 months49 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
Nutrients Exposures
Dietary: Fibre Folate Soy protein, isoflavones Total fat (g/d, % calories) Saturated fat Dietary patterns Alcohol
Other Exposures
Physical activity Total (work, home, commute, recreation) Recreational only
Body fatness Body mass index (kg/m2) Weight change
Randomised controlled trials
Women’s Intervention Nutrition Study (WINS): reducing dietary fat intake to 15% of total energy intake (Chlebowski, 2006); 2437 women (age 48-79 years)
Overall survival: HR 0.89 (95% CI 0.65-1.21) Relapse-free survival HR 0.76 (95% CI 0.60-0.98)
Women’s Healthy Eating and Living (WHEL Study): diet high in vegetables (daily intake of 5 servings plus 16 oz of vegetable juice), fruit (3 servings/day) and fibre (30 g/day) and low in fat (15-20% of energy intake that was kept isocaloric) (Pierce, 2007); 3088 women (age 18-70 years)
Overall survival: HR :0.91 (95% CI 0.72-1.15; p = 0.43). Disease-free survival HR 0.96 (95% CI 0.80-1.14).
Barnett GC 2008
Hellmann 2010
Reding KW 2008
Harris HR 2012
Zhang S 1995
Dal Maso L 2008
0 5 10 15 20 25
Alcohol pre-diagnosis (drinks/week)
Overall (I-squared = 0.0%, p = 0.564)
Saxe GA (1999)
Dal Maso L (2008)
Zhang S (1995)
Hellmann (2010)
Reding KW (2008)
Harris HR (2012)
Barnett GC (2008)
Study
1.00 (0.99, 1.00)
1.01 (0.91, 1.13)
0.99 (0.96, 1.02)
0.93 (0.81, 1.07)
1.00 (0.98, 1.02)
0.97 (0.95, 1.00)
0.99 (0.95, 1.03)
1.00 (0.99, 1.01)
100.00
0.50
6.61
0.31
19.51
8.55
4.12
60.39
Weight
%
1.00 (0.99, 1.00)
1.01 (0.91, 1.13)
0.99 (0.96, 1.02)
0.93 (0.81, 1.07)
1.00 (0.98, 1.02)
0.97 (0.95, 1.00)
0.99 (0.95, 1.03)
1.00 (0.99, 1.01)
RR (95% CI)Per 1 drink/week
100.00
0.50
6.61
0.31
19.51
8.55
4.12
60.39
Weight%
1.9 1 1.2
Alcohol (before diagnosis) and total mortality
Linear dose-response meta-analysis of alcohol consumption (before diagnosis) and total
mortality
Alcohol (after diagnosis) and total mortality
Linear dose-response meta-analysis of alcohol consumption (twelve months or more after
diagnosis) and total mortality
Overall (I-squared = 50.2%, p = 0.074)
Flatt S (2010)
Study
Holmes MD (1999)
Barnett GC (2008)
Beasley JM (2011)
Kwan M (2010)
Ewertz M (1991)
0.98 (0.93, 1.03)
0.77 (0.61, 0.97)
1.01 (0.88, 1.15)
0.98 (0.96, 0.99)
0.94 (0.88, 1.00)
1.22 (0.86, 1.72)
RR (95% CI)
1.07 (0.96, 1.18)
100.00
4.61
10.91
40.78
25.83
2.17
Weight
15.70
0.98 (0.93, 1.03)
0.77 (0.61, 0.97)
1.01 (0.88, 1.15)
0.98 (0.96, 0.99)
0.94 (0.88, 1.00)
1.22 (0.86, 1.72)
RR (95% CI) Per 10 g/day
1.07 (0.96, 1.18)
100.00
4.61
%
10.91
40.78
25.83
2.17
Weight
15.70
1.6 1 1.2
Barnett GC 2008
Flatt S 2010
Ewertz M 1991
Beasley JM 2011
Holmes MD 1999
Kwan M 2010
0 10 20 30 40
Alcohol post-diagnosis (g/day)
Linear dose-response meta-analysis of alcohol intake before breast cancer diagnosis and breast cancer mortality
Overall (I-squared = 73.5%, p = 0.010)
Hellmann (2010)
Study
Dal Maso L (2008)
Harris HR (2012)
Reding KW (2008)
1.00 (0.97, 1.02)
1.01 (0.98, 1.03)
1.00 (0.99, 1.02)
1.02 (0.97, 1.08)
0.96 (0.93, 0.98)
100.00
26.13
33.62
14.22
26.03
Weight
1.00 (0.97, 1.02)
1.01 (0.98, 1.03)
1.00 (0.99, 1.02)
1.02 (0.97, 1.08)
0.96 (0.93, 0.98)
RR (95% CI) per 1 drink/week
100.00
26.13
%
33.62
14.22
26.03
Weight
1.9 1 1.1
Hellmann 2010
Dal Maso L 2008
Reding KW 2008
Harris HR 2012
0 5 10 15 20
Alcohol pre-diagnosis (drinks/week)
Alcohol (before diagnosis) and breast cancer mortality
Alcohol (after diagnosis) and breast cancer mortality
Linear dose-response meta-analysis of alcohol consumption (twelve months or more after
diagnosis) and breast cancer mortality
Overall (I-squared = 65.2%, p = 0.057)
Study
Rohan T (1993)
Beasley JM (2011)
Kwan M (2010)
1.06 (0.79, 1.42)
RR (95% CI)Per 10 g/day
0.78 (0.55, 1.11)
1.06 (0.94, 1.20)
1.58 (1.00, 2.50)
100.00
Weight
29.58
47.61
22.81
1.06 (0.79, 1.42)
0.78 (0.55, 1.11)
1.06 (0.94, 1.20)
1.58 (1.00, 2.50)
100.00
%
Weight
29.58
47.61
22.81
1.6 1 1.7
Beasley JM 2011
Rohan T 1993
Kwan M 2010
0 10 20 30 40
Alcohol post-diagnosis (g/day)
Summary: Alcohol
Total mortalityBreast 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. Low2650 0.93 (0.82-1.06) 1329 1.18 (0.81-1.72) - -
Before : Per 1
drink/week2676
1.00 (0.99-1.00)1296
1.00 (0.97-1.02) - -
After diagnosis:
High vs. Low3827
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)
Dietary fibre
NOTE: Weights are from random effects analysis
Overall (I-squared = 0.0%, p = 0.968)
Beasley JM (2011)
Holmes MD (1999)
Study
Belle F (2011)
0.88 (0.78, 0.99)
0.87 (0.73, 1.04)
0.90 (0.73, 1.10)
0.87 (0.65, 1.16)
100.00
46.15
36.00
Weight
17.85
0.88 (0.78, 0.99)
0.87 (0.73, 1.04)
0.90 (0.73, 1.10)
RR (95% CI)Per 10 g/day
0.87 (0.65, 1.16)
100.00
46.15
36.00
%Weight
17.85
1.8 1 1.2
Linear dose-response meta-analysis of fibre intake (twelve months or more after diagnosis)
NOTE: Weights are from random effects analysis
Overall (I-squared = 0.0%, p = 0.643)
Rohan T (1993)
Study
Belle F (2011)
Beasley JM (2011)
0.93 (0.80, 1.07)
0.96 (0.80, 1.16)
0.94 (0.68, 1.29)
0.80 (0.58, 1.12)
100.00
59.97
%
20.75
Weight
19.28
0.93 (0.80, 1.07)
0.96 (0.80, 1.16)
0.94 (0.68, 1.29)
RR (95% CI)Per 10 g/day
0.80 (0.58, 1.12)
%Weight
1.6 1 1.2
Total mortality Breast cancer mortality
Dietary fibre Summary
Total mortality Breast cancer mortality
N deaths (studies)
RR (95%CI)I2, Pheterogeneity
N deaths(studies)
RR (95%CI)I2, Pheterogeneity
Before diagnosis
High vs. Low 417 (2) 0.50 (0.35-0.73)0%, p = 0.83
Per 10 g/day443 (3) 0.68 (0.56-0.84)
0%, p = 0.41
Twelve months or more after diagnosis
High vs. Low1092 (3) 0.76 (0.58-0.98)
0%, p = 0.99332 (3) 0.82 (0.57-1.20)
0%, p = 0.95
Per 10 g/day1092 (3) 0.88(0.78-0.99)
0%, p = 0.97332 (3) 0.93 (0.80-1.07)
0%, p = 0.64
Vegetables, total mortality
.
.
.
Pre-menopausal
Fink B (2006)
Saxe GA (1999)
Subtotal (I-squared = 0.0%, p = 0.876)
Pre and post-menopausal
Fink B (2006)
Saxe GA (1999)
Subtotal (I-squared = 0.0%, p = 0.866)
Post-menopausal
Buck K (2011)
Fink B (2006)
McEligot A (2006)
Saxe GA (1999)
Subtotal (I-squared = 24.7%, p = 0.263)
Study
1.02 (0.96, 1.08)
0.96 (0.45, 2.02)
1.02 (0.96, 1.08)
1.00 (0.96, 1.03)
0.97 (0.70, 1.35)
1.00 (0.96, 1.03)
1.03 (0.93, 1.14)
0.99 (0.94, 1.03)
0.93 (0.87, 0.99)
0.95 (0.65, 1.39)
0.97 (0.93, 1.02)
99.43
0.57
100.00
98.90
1.10
100.00
15.49
49.64
33.59
1.28
100.00
Weight
%
1.02 (0.96, 1.08)
0.96 (0.45, 2.02)
1.02 (0.96, 1.08)
1.00 (0.96, 1.03)
0.97 (0.70, 1.35)
1.00 (0.96, 1.03)
1.03 (0.93, 1.14)
0.99 (0.94, 1.03)
0.93 (0.87, 0.99)
0.95 (0.65, 1.39)
0.97 (0.93, 1.02)
RR (95% CI)Per 3 serving/week
99.43
0.57
100.00
98.90
1.10
100.00
15.49
49.64
33.59
1.28
100.00
Weight
%
1.7 1 1.4
Fruits, total mortality
.
.
.
Pre-menopausalFink B (2006)Saxe GA (1999)
Subtotal (I-squared = 46.2%, p = 0.173)
Pre and post-menopausalFink B (2006)Saxe GA (1999)
Subtotal (I-squared = 0.0%, p = 0.715)
Post-menopausalBuck K (2011)Fink B (2006)McEligot A (2006)
Saxe GA (1999)Subtotal (I-squared = 22.4%, p = 0.276)
Study
1.03 (0.87, 1.22)0.41 (0.11, 1.52)
0.83 (0.38, 1.78)
0.98 (0.91, 1.05)1.02 (0.83, 1.27)
0.98 (0.92, 1.05)
0.93 (0.81, 1.07)0.97 (0.89, 1.05)0.80 (0.62, 1.03)
1.11 (0.89, 1.38)0.96 (0.88, 1.04)
RR (95% CI)Per 7 serving/week
76.0223.98
100.00
89.0610.94
100.00
26.9850.809.74
12.48100.00
Weight
%
1.03 (0.87, 1.22)0.41 (0.11, 1.52)
0.83 (0.38, 1.78)
0.98 (0.91, 1.05)1.02 (0.83, 1.27)
0.98 (0.92, 1.05)
0.93 (0.81, 1.07)0.97 (0.89, 1.05)0.80 (0.62, 1.03)
1.11 (0.89, 1.38)0.96 (0.88, 1.04)
76.0223.98
100.00
89.0610.94
100.00
26.9850.809.74
12.48100.00
Weight
%
1.6 1 1.7
Linear dose-response meta-analysis of fruits and vegetable intake (before diagnosis)
Fruits and vegetables
Isoflavones intake and total mortality
Meta-analysis of isoflavones intake (highest compared to lowest intake) and total mortality
Overall (I-squared = 59.4%, p = 0.061)
Fink B (2007)
Kang X premenopausal (2010)
Study
Boyapati SM (2005)
Kang X postmenopausal (2010)
0.87 (0.65, 1.17)
0.52 (0.33, 0.82)
1.05 (0.78, 1.71)
1.06 (0.79, 1.42)
0.88 (0.56, 1.24)
100.00
21.31
Weight
24.43
30.09
24.17
>7.48 vs 0-0.29 mg/d
Comparison
>42.3 vs <15.2 mg/d
T3 vs T1
>42.3 vs <15.2 mg/d
0.87 (0.65, 1.17)
0.52 (0.33, 0.82)
RR (95% CI)High vs low
1.05 (0.78, 1.71)
1.06 (0.79, 1.42)
0.88 (0.56, 1.24)
100.00
21.31
Weight
24.43
%
30.09
24.17
1.2 1 2
Overall (I-squared = 8.1%, p = 0.337)
Zhang Y (2012)
Shu X (2009)
Caan B (2011)
Study
0.70 (0.56, 0.88)
0.62 (0.42, 0.90)
0.79 (0.61, 1.03)
0.46 (0.20, 1.05)
100.00
31.84
60.88
Weight%
7.28
>28.83 vs <7.56 mg/d
>62.68 vs <=20 mg/d
Comparison
16.33-86.9 vs 0-0.07 mg/d
0.70 (0.56, 0.88)
0.62 (0.42, 0.90)
0.79 (0.61, 1.03)
RR (95% CI)High vs low
0.46 (0.20, 1.05)
100.00
31.84
60.88
7.28
1.2 11.5
Before diagnosis Twelve months or more after diagnosis
Overall (I-squared = 82.0%, p = 0.001)
Zhang S
Gregorio DI
Saxe GA
McEligot A
Author
1995
1985
1999
2006
Year
1.19 (1.01, 1.41)
1.13 (1.01, 1.28)
1.04 (1.00, 1.08)
1.15 (0.82, 1.61)
1.63 (1.31, 2.03)
RR (95% CI)Per 10 g/day
100.00
29.69
34.38
14.33
21.61
Weight
1.19 (1.01, 1.41)
1.13 (1.01, 1.28)
1.04 (1.00, 1.08)
1.15 (0.82, 1.61)
1.63 (1.31, 2.03)
100.00
%
29.69
34.38
14.33
21.61
Weight
1.492 1 2.03
Total mortalityLinear dose-response meta-analysis
Overall (I-squared = 53.5%, p = 0.091)
Dal Maso L
Nomura AM
Author
Kyogoku
Jain M
2008
1991
Year
1992
1994
1.13 (0.71, 1.77)
0.95 (0.75, 1.22)
1.42 (0.71, 2.86)
0.40 (0.10, 1.30)
1.89 (0.96, 3.70)
100.00
43.28
22.93
Weight%
10.06
23.73
T3 vs T1
High vs Low
Comparison
Q4 vs Q1
>=45.2 vs <=38.08%energy
1.13 (0.71, 1.77)
0.95 (0.75, 1.22)
1.42 (0.71, 2.86)
RR (95% CI)
0.40 (0.10, 1.30)
1.89 (0.96, 3.70)
High vs low fat
100.00
43.28
22.93
10.06
23.73
1.1 1 10
Fat intake before diagnosis
Breast cancer mortalityHighest vs lowest meta-analysis
Total mortalityHighest vs lowest meta-analysis
Fat intake twelve months or more after diagnosis
Breast cancer mortalityHighest vs lowest meta-analysis
NOTE: Weights are from random effects analysis
Overall (I-squared = 0.0%, p = 0.413)
Author
Holmes MD
Newman S
Beasley JM
Rohan T
Year
1999
1986
2011
1993
1.19 (0.94, 1.50)
1.44 (1.01, 2.04)
0.99 (0.65, 1.51)
0.92 (0.53, 1.60)
1.40 (0.66, 2.96)
100.00
Weight
43.33
29.63
17.54
9.51
Comparison
>=69.6 vs <53g/day
>77 vs <=77 g/day
mean 39 vs 23%energy
>108 vs <56 g/day
1.19 (0.94, 1.50)
RR (95% CI)High vs low
1.44 (1.01, 2.04)
0.99 (0.65, 1.51)
0.92 (0.53, 1.60)
1.40 (0.66, 2.96)
100.00
Weight%
43.33
29.63
17.54
9.51
1.338 1 2.96
Overall (I-squared = 24.4%, p = 0.266)
Ewertz M
Author
Beasley JM
Holmes MD
1991
Year
2011
1999
1.08 (0.90, 1.30)
0.96 (0.75, 1.22)
1.05 (0.79, 1.39)
1.34 (0.97, 1.85)
100.00
40.70
Weight%
32.73
26.57
Q4 vs Q1
Comparison
mean 39 vs 23%energy
>=69.6 vs <53g/day
1.08 (0.90, 1.30)
0.96 (0.75, 1.22)
RR (95% CI)High vs low
1.05 (0.79, 1.39)
1.34 (0.97, 1.85)
100.00
40.70
32.73
26.57
1.541 1 1.85
Fat intakeSummary
Total mortality Breast cancer mortality
N deaths (studies)
RR (95%CI)I2, Pheterogeneity
N deaths(studies)
RR (95%CI)I2, Pheterogeneity
Before diagnosis
High vs. Low 655 (3) 1.87 (0.76-4.57)90.1%,p < 0.001
521 (4) 1.13 (0.71-1.77)53.5%, p = 0.09
Per 10 g/day178 (4) 1.19 (1.01-1.41)
82.0%, p=0.001
Twelve months or more after diagnosis
High vs. Low1436 (3) 1.08 (0.90-1.30)
24.4%, p = 0.27648 (4) 1.19 (0.94-1.50)
0%, p = 0.41
Per 10 g/day575 (3) 1.01 (0.95-1.08)
24.0%, p = 0.27
Saturated fat intake before diagnosis
and total mortality
Overall (I-squared = 31.8%, p = 0.231)
McEligot A
Author
Saxe GA
Zhang S
2006
Year
1999
1995
1.66 (1.26, 2.19)
2.02 (1.50, 2.70)
1.20 (0.56, 2.57)
1.45 (1.04, 2.03)
100.00
47.46
Weight
11.71
40.83
1.66 (1.26, 2.19)
2.02 (1.50, 2.70)
RR (95% CI)Per 10 g/day
1.20 (0.56, 2.57)
1.45 (1.04, 2.03)
100.00
47.46
%
11.71
40.83
1.37 1 2.7
Issues Relevant to Survivor Research
Confounding effects of: Treatment types, efficacies, adverse effects Stage of disease Comorbidities Type of cancer
Methodological: Assessing exposure Determining cause of death Determining and classifying recurrence Screening for second primary breast cancer Increasing length of survival
Summary
Growing literature on nutrition, related factors, & breast cancer survival
Time of exposure is dynamic Various outcomes are important to study Data are sufficient for meta-analyses for
several variables but still limited Some evidence that a healthy diet (rich in plant
foods and low in saturated fats) may be related to longer survival in breast cancer patients
Judgement
The Reports from World Cancer Research Fund/American Institute for Cancer Research and the Systematic Literature Reviews published on October 16 2014 in www.wcrf.org
Thanks! Continuous Update Project Panel
Anne Mc Tiernan and Inger Thune International scientific experts CUP team