School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Pre- and post-diagnostic lifestyle factors and mortality in women with breast cancer Mona Jeffreys School of Social and Community Medicine

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 )

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Breast cancer incidence

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL (Un)modifiable risk factors  Age  BRCA genes (family history)  Breast density  Benign breast disease  Birthweight, growth, height

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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, smoking

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Breast cancer survival

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 population

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 rate

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Lifestyle determinants of survival

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Lifestyle determinants of survival  Good evidence of lower survival in overweight women

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Obesity and all cause mortality Protani, BCRT 2010

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Obesity and breast-cancer specific mortality Protani, BCRT 2010

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL But is it all confounding?  Women’s Intervention Nutrition Study  RCT of 2437 women, aged  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)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL But is it all confounding?  Women’s Healthy Eating and Living  RCT of 3088 women, aged  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)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Physical activity and breast cancer outcomes Patterson 2010,

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Diet and breast cancer outcomes Patterson 2010,

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Diet and breast cancer outcomes (cont’d) Patterson 2010,

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL New Zealand Breast Cancer Study  Nationwide multi-ethnic, age- and ethnicity- matched population-based case-control study  Over-sampling of Māori and Pacific women

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Methods  Cases identified from Cancer Registry  April 2006 to April 2007  Māori and Pacific cases to April 2008  Controls from Electoral Roll  General  Māori  Additional methods for Pacific controls GP and community-based

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Response rates (cases) 1,799 cases 302 (81%) Māori, 70 (46%) Pacific, 1,427 (78%) non- Māori /non-Pacific

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Exposures  BMI and WHR  Smoking  Alcohol  Physical activity  Diet  Servings of F&V, meat (red/white), fish, milk, cream, cheese

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Timing of exposure  Lifetime  “In the last year, on average...” Within 1 yearAfter 1 year Number (%)1,237 (71.5%)492 (28.5%) Median7.9 months22.3 months Range4 to 12 months12 to 39 months

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 mortality

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Basic results MāorinMnP Total3021,427 Deaths21 (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 age54.3 (47.0 to 62.8)57.9 (49.1 to 67.6) Interviewed after 1 year152 (50%)340 (24%)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Follow-up by ethnicity Log rank test P=0.56

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of BMI on survival Log rank test P=0.21

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of BMI on survival BMI (kg/m 2 ) <2525 to 30>=30 Adjusted* (0.50 to 1.24)0.73 (0.44 to 1.21) Pre-diagnostic (0.52 to 1.44)0.87 (0.49 to 1.54) Post-diagnostic (0.15 to 1.56)0.39 (0.14 to 1.13) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of WHR on survival Log rank test P=0.085

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of WHR on survival Waist – hip ratio Tertile 1Tertile 2Tertile 3 Adjusted* (0.74 to 1.97)1.35 (0.82 to 2.22) Pre-diagnostic (0.65 to 1.95)1.48 (0.86 to 2.56) Post-diagnostic (0.53 to 5.73)1.13 (0.32 to 4.06) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival Newcomb, JCO 2013

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival Newcomb, JCO 2013

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Alcohol frequency and amount Alcohol frequency Never <=1/mthUp to 1/wk2-3/wk4+/wk Alcohol amount None drinks drinks drinks drinks or more08893 Nil, slight, moderate, heavy Used “slight” as the reference group

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival Log rank test P=0.14

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival: overall Alcohol intake NoneSlightModerateHeavy Adjusted*0.95 (0.57 to 1.58) (0.58 to 1.49)1.96 (0.98 to 3.94) Pre-diagnostic 0.79 (0.43 to 1.49) (0.56 to 1.57)1.39 (0.57 to 3.34) Post-diagnostic1.61 (0.64 to 4.06) (0.12 to 2.73)4.82 (1.43 to 16.29) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival: frequency Alcohol intake (frequency) Never≤1/mthUp to 1/wk2+/wk Adjusted*1.08 (0.61 to 1.90) (0.82 to 2.72) 1.18 (0.70 to 1.98) Adjusted**1.19 (0.66 to 2.16) (0.86 to 3.09) 1.26 (0.73 to 2.19) Pre- diagnostic** 0.82 (0.41 to 1.64) (0.50 to 2.21) 0.95 (0.52 to 1.71) Post- diagnostic** 4.88 (1.22 to 19.61) (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 amount

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of alcohol on survival: amount Alcohol intake (drinks per day) None Adjusted*0.98 (0.61 to 1.58) (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) (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) (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) (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 frequency

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Smoking  Have you ever smoked, now or in the past?  Are you a current smoker?  Categorised into never, current, ex- smokers

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of smoking on survival Log rank test P=0.66

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of smoking on survival Smoking Never smokedEx-smokersCurrent smokers Adjusted* (0.69 to 1.58)1.43 (0.76 to 2.68) Pre-diagnostic (0.59 to 1.50)1.36 (0.63 to 2.93) Post-diagnostic (0.70 to 5.41)2.31 (0.65 to 8.28) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Physical activity  Measured using Godin questionnaire  Frequency of mild, moderate and strenuous  Analysed in quartiles  Lowest quartile designated as “sedentary”

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of physical activity on survival Log rank test P=0.146

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease Effect of physical activity on survival Physical activity ActiveSedentary Adjusted* (0.74 to 1.69) Pre-diagnostic (0.57 to 1.52) Post-diagnostic (0.90 to 4.60)

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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?

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of fruit and vegetable intake on survival Fruit intake (>14 servings per week) Vegetable intake (>21 servings per week) NoYesNoYes Adjusted* (0.96 to 2.10) (0.91 to 2.19) Pre-diagnostic (0.92 to 2.22) (0.84 to 2.29) Post-diagnostic (0.54 to 3.00) (0.55 to 3.73) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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  Smoking

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Other dietary measures  No clear relationship with intake of  Milk  Cream  Cheese  Meat (red/white)  Fish

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Dairy intake and cancer survival

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Dairy intake and cancer survival Kroenke, JNCI 2013

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Limitations of NZ study  Poor measurement of some exposures  Particularly dietary measures  What time frame are women actually reporting on?

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of childhood fruit and vegetable intake on survival Fruit intake (days/week) Vegetable intake (days/week) <=45+<=45+ Adjusted* (0.74 to 1.62) (0.28 to 0.83) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Effect of childhood fruit and vegetable intake on survival Fruit intake (days/week) Vegetable intake (days/week) <=45+<=45+ Adjusted* (0.74 to 1.62) (0.28 to 0.83) Pre-diagnostic (0.87 to 2.19) (0.24 to 0.82) Post- diagnostic (0.20 to 1.08) (0.20 to 1.84) * Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Determinants of high F&V reporting Fruit intake (>14 servings per week) Vegetable intake (>21 servings per week) Childhood F&V1.86 (1.42 to 2.46)1.65 (1.28 to 2.13) Ever smoked0.71 (0.57 to 0.88)1.00 (0.79 to 1.28) Ethnicity0.87 (0.65 to 1.16)0.83 (0.59 to 1.16) Unrelated: area deprivation, childhood SEP, age, menopausal status, extent of disease

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Determinants of high F&V reporting Fruit intake (>14 servings per week) Vegetable intake (>21 servings per week) Childhood F&V1.86 (1.42 to 2.46)1.65 (1.28 to 2.13) Ever smoked0.71 (0.57 to 0.88)1.00 (0.79 to 1.28) Ethnicity0.87 (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

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 analyses

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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 mass

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL 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