Mona Jeffreys School of Social and Community Medicine Breast cancer Most common cancer in women in UK Affects approximately 50000 women in UK each year 851 of patients survive for five years or more diagnosed 20052009 ID: 617984
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Slide1
Pre- and post-diagnostic lifestyle factors and mortality in women with breast cancer
Mona Jeffreys
School of Social and Community MedicineSlide2
Breast cancer
Most common cancer in women in UK
Affects approximately 50,000 women in UK each year
85.1% of patients survive for five years or more (diagnosed 2005-2009)Slide3
Breast cancer incidence
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidenceSlide4
(Un)modifiable risk factors
Age
BRCA genes (family history)
Breast density
Benign breast disease
Birthweight
, growth, heightSlide5
Modifiable risk factors
Reproductive factors
Nulliparity
/ late age at first birth, early menarche, late menopause
, breastfeeding
Exogenous oestrogens (
OC, HRT)
Shiftwork
Diet
Saturated fat,
phyto
-oestrogens, fibre
Lifestyle
Body weight, alcohol, physical activity, smokingSlide6
Breast cancer survival
http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/survival
/Slide7
Relative survival
Survival “adjusted for” background mortality (excess mortality “due” to cancer)
Avoids need for cause of death
Observed : expected survival ratio
Compares “observed” survival in the cancer population to “expected” survival in general populationSlide8
Relative survival (cont’d)
Life-table methods (census)
May not be valid when “observed” and “expected” groups have a different underlying expected mortality
Compare ethnic groups
Cohort study with low response rateSlide9
Lifestyle determinants of survivalSlide10
Lifestyle determinants of survival
Good evidence of lower survival in overweight womenSlide11
Obesity and all cause mortality
Protani
, BCRT 2010Slide12
Obesity and breast-cancer specific mortality
Protani
, BCRT 2010Slide13
But is it all confounding?
Women’s Intervention Nutrition Study
RCT of 2437 women, aged 43-79
Early stage breast cancer
Intervention: dietary fat reduction
Associated weight loss (2kg difference at 3 years)
Lower recurrence in intervention group (9.8%
vs
12.4%, HR
0.76 (95% CI = 0.60 to 0.98
)Slide14
But is it all confounding?
Women’s Healthy Eating and Living
RCT of 3088 women, aged 18-70
Early stage breast cancer
Intervention: High F&V,
fibre
and low fat
No change in body weight or energy intake
No difference in breast cancer events (HR
0.96, CI: 0.80 to 1.14)
or mortality (HR
0.91; CI: 0.72 to 1.15)
Interaction with PA: reduced mortality in women with high F&V and high PA, irrespective of obesity (HR
0.56; CI
:
0.31 to 0.98
)Slide15
Physical activity and breast cancer outcomes
Patterson 2010, h
ttp://dx.doi.org/10.1016/j.maturitas.2010.01.004Slide16
Diet and breast cancer outcomes
Patterson 2010, h
ttp://dx.doi.org/10.1016/j.maturitas.2010.01.004Slide17
Diet and breast cancer outcomes (cont’d)
Patterson 2010, h
ttp://dx.doi.org/10.1016/j.maturitas.2010.01.004Slide18
New Zealand Breast Cancer Study
Nationwide multi-ethnic, age- and ethnicity-matched population-based case-control study
Over-sampling of Māori and Pacific womenSlide19
Methods
Cases identified from Cancer Registry
April 2006 to April 2007
M
ā
ori
and Pacific cases to April 2008
Controls from Electoral Roll
General
M
ā
ori
Additional methods for Pacific controls
GP and community-basedSlide20
Response rates (cases)
1,799 cases
302 (81%) Māori,
70 (46%) Pacific,
1,427 (78%) non-Māori /non-PacificSlide21
Exposures
BMI and WHR
Smoking
Alcohol
Physical activity
Diet
Servings of F&V, meat (red/white), fish, milk, cream, cheeseSlide22
Timing of exposure
Lifetime
“In the last year, on average...”
Within 1 year
After 1 year
Number (%)
1,237 (71.5%)
492 (28.5%)
Median
7.9 months
22.3 months
Range
4 to 12 months
12 to 39 monthsSlide23
Ascertainment of outcome
Linked to death register
Covers all of New Zealand
Requires ethical approval
Censored at 28/02/2009
Not valid for Pacific women
“
Going home to die”
Informed of date of death but not cause
All cause mortalitySlide24
Statistical methods
Kaplan Meier curves
Log rank tests
Cox regression
Followed from time of diagnosis to dead / censoring
Adjusted for age at diagnosis, menopausal status, interview method, extent of disease at diagnosis (stage)Slide25
Basic results
Māori
nMnP
Total
302
1,427
Deaths
21 (7.0%)
109 (7.6%)
Follow-up (years)
2.92 (1.1 to
3.9 yrs)
3.29 (11
mths
to 3.9 yrs)
Median age
54.3 (47.0 to 62.8)
57.9 (49.1 to 67.6)
Interviewed after 1 year
152 (50%)
340 (24%)Slide26
Follow-up by ethnicity
Log rank test
P=0.56Slide27
Effect of BMI on survival
Log rank test
P=0.21Slide28
Effect of BMI on survival
BMI (kg/m
2
)
<25
25 to 30
>=30
Adjusted*
1.00
0.79 (0.50 to 1.24)
0.73 (0.44 to 1.21)
Pre-diagnostic
1.00
0.86 (0.52 to 1.44)
0.87 (0.49 to 1.54)
Post-diagnostic
1.00
0.49 (0.15 to 1.56)
0.39 (0.14 to 1.13)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide29
Effect of WHR on survival
Log rank test
P=0.085Slide30
Effect of WHR on survival
Waist – hip ratio
Tertile
1
Tertile
2
Tertile
3
Adjusted*
1.00
1.20 (0.74
to 1.97)
1.35 (0.82 to 2.22)
Pre-diagnostic
1.00
1.13 (0.65 to 1.95)
1.48 (0.86 to 2.56)
Post-diagnostic
1.00
1.74 (0.53 to 5.73)
1.13 (0.32 to 4.06)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide31
Effect of alcohol on survivalSlide32
Effect of alcohol on survival
Newcomb, JCO 2013Slide33
Effect of alcohol on survival
Newcomb, JCO 2013Slide34
Measurement of alcohol
How often did you have a drink containing alcohol? (frequency)
How many drinks containing alcohol did you have on a typical day when you are drinking? (amount)Slide35
Alcohol frequency and amount
Alcohol frequency
Never
<=1/
mth
Up to 1/wk
2-3/wk
4+/wk
Alcohol amount
None
334
0
0
0
0
1-2 drinks
0
354
221
209
257
3-4
drinks
0
20
50
62
61
5-6 drinks
0
16
15
17
17
7-9 drinks
0
10
3
3
8
10 or
more
0
8
8
9
3
Nil
,
slight
,
moderate
,
heavy
Used “slight” as the reference groupSlide36
Effect of alcohol on survival
Log rank test
P=0.14Slide37
Effect of alcohol on survival: overall
Alcohol intake
None
Slight
Moderate
Heavy
Adjusted*
0.95 (0.57 to 1.58)
1.00
0.93 (0.58 to 1.49)
1.96 (0.98 to 3.94)
Pre-diagnostic
0.79 (0.43 to 1.49)
1.00
0.94 (0.56 to 1.57)
1.39 (0.57 to 3.34)
Post-diagnostic
1.61 (0.64 to 4.06)
1.00
0.57 (0.12 to 2.73)
4.82 (1.43 to 16.29)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide38
Effect of alcohol on survival: frequency
Alcohol intake (frequency)
Never
≤1/
mth
Up to 1/wk
2+/wk
Adjusted*
1.08
(0.61 to 1.90)
1.00
1.49
(0.82 to 2.72)
1.18
(0.70 to 1.98)
Adjusted**
1.19
(0.66 to 2.16)
1.00
1.63
(0.86 to 3.09)
1.26
(0.73 to 2.19)
Pre-diagnostic**
0.82
(0.41 to 1.64)
1.00
1.05
(0.50 to 2.21)
0.95
(0.52 to 1.71)
Post-diagnostic**
4.88
(1.22 to 19.61)
1.00
8.25
(1.93 to 35.22)
3.80
(0.82 to 17.63)
Merged categories 2-3 per week and 4+ per week
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
** Also adjusted for alcohol amountSlide39
Effect of alcohol on survival: amount
Alcohol intake (drinks per day)
None
1-2
3-4
5-6
7+
Adjusted*
0.98
(0.61 to 1.58)
1.00
0.97
(0.48 to 1.97)
1.33
(0.48 to 3.74)
2.36
(0.79 to 7.07)
Adjusted**
1.19
(0.66 to 2.15)
1.00
0.93
(0.45 to 1.90)
1.36
(0.49 to 3.83)
2.39
(0.80 to 7.18)
Pre-diagnostic**
0.83
(0.41 to 1.66)
1.00
1.06
(0.49 to 2.30)
0.94
(0.22 to 3.93)
1.87
(0.40 to 8.80)
Post-diagnostic**
4.53
(1.15 to 17.80)
1.00
0.54
(0.07 to 4.33)
2.85
(0.56 to 14.53)
3.41
(0.54 to 21.30)
Merged categories 7-9 and 10+ drinks per day
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
** Also adjusted for alcohol frequencySlide40
Smoking
Have you ever smoked, now or in the past?
Are you a current smoker?
Categorised into never, current, ex-smokersSlide41
Effect of smoking on survival
Log rank test
P=0.66Slide42
Effect of smoking on survival
Smoking
Never smoked
Ex-smokers
Current smokers
Adjusted*
1.00
1.05 (0.69 to 1.58)
1.43 (0.76
to 2.68)
Pre-diagnostic
1.00
0.94 (0.59 to 1.50)
1.36 (0.63 to 2.93)
Post-diagnostic
1.00
1.95 (0.70 to 5.41)
2.31 (0.65 to 8.28)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide43
Physical activity
Measured using
Godin
questionnaire
Frequency of mild, moderate and strenuous
Analysed in quartiles
Lowest quartile designated as “sedentary”Slide44
Effect of physical activity on survival
Log rank test
P=0.146Slide45
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
Effect of physical activity on survival
Physical
activity
Active
Sedentary
Adjusted*
1.00
1.12 (0.74
to 1.69)
Pre-diagnostic
1.00
0.93 (0.57 to 1.52)
Post-diagnostic
1.00
2.03 (0.90 to 4.60)Slide46
Fruit and vegetable intake
How many servings of
vegetables
(excluding potatoes) did you usually eat each week?
How many servings of
fruit
did you usually eat each week?Slide47
Effect of
fruit and vegetable intake on survival
Fruit intake
(>14 servings per week)
Vegetable intake
(>21 servings per week)
No
Yes
No
Yes
Adjusted*
1.00
1.42 (0.96 to
2.10)
1.00
1.41 (0.91 to 2.19)
Pre-diagnostic
1.00
1.43 (0.92 to 2.22)
1.00
1.39 (0.84 to 2.29)
Post-diagnostic
1.00
1.27 (0.54 to 3.00)
1.00
1.44 (0.55 to 3.73)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide48
Summary
Suggestion of poorer survival in women who were
Had lower BMI, but higher WHR
Never and heavy alcohol drinkers
Sedentary
No clear relationship with
F&V intake
SmokingSlide49
Other dietary measures
No clear relationship with intake of
Milk
Cream
Cheese
Meat (red/white)
FishSlide50
Dairy intake and cancer survivalSlide51
Dairy intake and cancer survival
Kroenke
, JNCI 2013Slide52
Limitations of NZ study
Poor measurement of some exposures
Particularly dietary measures
What time frame are women actually reporting on?Slide53
Effect of childhood
fruit and vegetable intake on survival
Fruit intake
(days/week)
Vegetable intake
(days/week)
<=4
5+
<=4
5+
Adjusted*
1.00
1.09 (0.74 to
1.62)
1.00
0.48 (0.28 to 0.83)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide54
Effect of childhood
fruit and vegetable intake on survival
Fruit intake
(days/week)
Vegetable intake
(days/week)
<=4
5+
<=4
5+
Adjusted*
1.00
1.09 (0.74 to
1.62)
1.00
0.48 (0.28 to 0.83)
Pre-diagnostic
1.00
1.39 (0.87 to 2.19)
1.00
0.44 (0.24 to 0.82)
Post-diagnostic
1.00
0.47 (0.20 to 1.08)
1.00
0.61 (0.20 to 1.84)
* Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseSlide55
Determinants of high F&V reporting
Fruit intake
(>14 servings per week)
Vegetable intake
(>21 servings per week)
Childhood F&V
1.86 (1.42 to 2.46)
1.65 (1.28 to 2.13)
Ever smoked
0.71 (0.57 to 0.88)
1.00 (0.79 to 1.28)
Ethnicity
0.87 (0.65 to 1.16)
0.83 (0.59 to 1.16)
Unrelated: area deprivation, childhood SEP, age, menopausal status, extent of disease Slide56
Determinants of high F&V reporting
Fruit intake
(>14 servings per week)
Vegetable intake
(>21 servings per week)
Childhood F&V
1.86 (1.42 to 2.46)
1.65 (1.28 to 2.13)
Ever smoked
0.71 (0.57 to 0.88)
1.00 (0.79 to 1.28)
Ethnicity
0.87 (0.65 to 1.16)
0.83 (0.59 to 1.16)
Interviewed after 1 year
1.15 (0.91 to 1.45)
1.50 (1.16 to 1.95)
Unrelated: area deprivation, childhood SEP, age, menopausal status, extent of disease Slide57
Limitations of NZ study
Poor measurement of some exposures
Particularly dietary measures
What time frame are women actually reporting on?
Pre- and post-diagnostic comparisons are not of the same women
Ideally have a measure of change
Survivor bias
Conditional survival
Limited statistical power for some analysesSlide58
Where next?
Re-analysis with longer follow-up
Physical activity intervention trial
acceptability of intervention and randomisation
Consider weight loss intervention
effect on lean body massSlide59
Acknowledgements
Co-PIs:
Lis
Ellison-
Loschmann
, Fiona McKenzie,
Riz
Firestone
Co-Investigators: Neil Pearce, Michelle Gray, Ate
Moala
,
Soo
Cheng
Funders:
New Zealand Lottery Grants Board
Massey University Research Fund
Health Research Council of New Zealand
Cancer Society of New Zealand