School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Pre- and post-diagnostic lifestyle...

School ofSOCIAL AND COMMUNITY

MEDICINE

University ofBRISTOL

Pre- and post-diagnostic lifestyle

factors and mortality in women with breast

cancer Mona Jeffreys

School of Social and Community Medicine

MEDICINE

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)

MEDICINE

Breast cancer incidence

http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence

MEDICINE

(Un)modifiable risk factors

Age BRCA genes (family history) Breast density Benign breast disease Birthweight, growth, height

MEDICINE

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

MEDICINE

Breast cancer survival

http://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/survival/

MEDICINE

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

MEDICINE

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

MEDICINE

Lifestyle determinants of survival

MEDICINE

Lifestyle determinants of survival

Good evidence of lower survival in overweight women

MEDICINE

Obesity and all cause mortality

Protani, BCRT 2010

MEDICINE

Obesity and breast-cancer specific mortality

Protani, BCRT 2010

MEDICINE

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)

MEDICINE

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)

MEDICINE

Physical activity and breast cancer outcomes

Patterson 2010, http://dx.doi.org/10.1016/j.maturitas.2010.01.004

MEDICINE

Diet and breast cancer outcomes

MEDICINE

Diet and breast cancer outcomes (cont’d)

MEDICINE

New Zealand Breast Cancer Study

Nationwide multi-ethnic, age- and ethnicity-matched population-based case-control study

Over-sampling of Māori and Pacific women

MEDICINE

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

MEDICINE

Response rates (cases)

1,799 cases

• 302 (81%) Māori,• 70 (46%) Pacific, • 1,427 (78%) non-

Māori /non-Pacific

MEDICINE

Exposures

BMI and WHR Smoking Alcohol Physical activity Diet

Servings of F&V, meat (red/white), fish, milk, cream, cheese

MEDICINE

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 months

MEDICINE

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

MEDICINE

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)

MEDICINE

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%)

MEDICINE

Follow-up by ethnicity0

0 1 year 3 years2 years 4 yearsFollow-up time

non-Maori/non-Pacific Maori

Kaplan-Meier survival estimates

Log rank testP=0.56

MEDICINE

Effect of BMI on survival0

1 year 2 years 3 years 4 years0analysis time

BMI <25 kg/m2 BMI 25-29.9 kg/m2BMI >=30 kg/m2

Log rank testP=0.21

MEDICINE

Effect of BMI on survivalBMI (kg/m2)

<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 disease

MEDICINE

Effect of WHR on survival0

0 1 year 2 years 3 years 4 yearsanalysis time

WHR tertile 1 WHR tertile 2WHR tertile 3

Log rank testP=0.085

MEDICINE

Effect of WHR on survivalWaist – 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)

MEDICINE

Effect of alcohol on survival

MEDICINE

Newcomb, JCO 2013

MEDICINE

Newcomb, JCO 2013

MEDICINE

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)

MEDICINE

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, heavyUsed “slight” as the reference group

MEDICINE

0 1 year 2 years 3 years 4 yearsanalysis time

Nil SlightModerate Heavy

Log rank testP=0.14

MEDICINE

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)

MEDICINE

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 amount

MEDICINE

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 frequency

MEDICINE

Smoking

Have you ever smoked, now or in the past?

Are you a current smoker? Categorised into never, current, ex-

smokers

MEDICINE

0 1 Year 2 Years 3 Years 4 Yearsanalysis time

Never smoker Ex-smokerCurrent smoker

Effect of smoking on survival

Log rank testP=0.66

MEDICINE

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)

MEDICINE

Physical activity

Measured using Godin questionnaire Frequency of mild, moderate and strenuous

Analysed in quartiles Lowest quartile designated as “sedentary”

MEDICINE

0 1 Year 2 Years 4 years3 Yearsanalysis time

active sedentary

Effect of physical activity on survival

Log rank testP=0.146

MEDICINE

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)

MEDICINE

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?

MEDICINE

Effect offruit and vegetable intake on

survivalFruit 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)

MEDICINE

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

MEDICINE

Other dietary measures

No clear relationship with intake of Milk Cream Cheese Meat (red/white) Fish

MEDICINE

Dairy intake and cancer survival

MEDICINE

Dairy intake and cancer survival

Kroenke, JNCI 2013

MEDICINE

Limitations of NZ study

Poor measurement of some exposures Particularly dietary measures What time frame are women actually reporting on?

MEDICINE

Effect of childhoodfruit and vegetable intake on

survivalFruit 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)

MEDICINE

Effect of childhoodfruit and vegetable intake on

survivalFruit 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)

MEDICINE

Determinants of high F&V reporting

Fruit intake(>14 servings per

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

MEDICINE

Determinants of high F&V reporting

Fruit intake(>14 servings per

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

MEDICINE

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

MEDICINE

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

MEDICINE

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

School of SOCIAL AND COMMUNITY MEDICINE University of BRISTOL Pre- and post-diagnostic lifestyle...

Documents

Mona Cv - Copy

MONA MONA WORLD TRAVELED AWARD WINNING 2 ... - Mambo Rock

Mona Kovacs' works

Mona Dajani

UWI Mona ClimateUWI Mona Climate--Energy Nexus Series ... · PDF fileUWI Mona ClimateUWI Mona Climate--Energy Nexus Series Energy Nexus Series ... 10%Petroleum Electricity ... (World

Bristol Flow Measurement Applications - Emerson Bristol Flow Measurement Applications Author: Bristol - Emerson Subject: Bristol Flow Measurement Applications Keywords: Bristol Created

Mona Gleason

Imran Series No. 103 - Mona Lisa Ki Nawasi (Mona Lisa Granddaughter)

Mona bdaypptfinal

THE MONA ECONOMIST

NIGHT_TENNIS_A3POSTER mona

Mona Lisa Mania. Mona Lisa by Da Vinci Young Mona Lisa by Botero

Geology of Isla Mona Puerto Rico, and Notes on Age of Mona

Revista mona

Mona Lisa Smile

MONA 2nd Internal

Mona bdaypptfinal3

mona mittal

Mona Island, Puerto Rico · MONA BOA The Mona Boa (ESA Threatened) is endemic to Mona Island. Due to its nocturnal habits and retiring nature, the Mona Boa, has been spared as victims

Mona Report