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: 1041108
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1. Pre- and post-diagnostic lifestyle factors and mortality in women with breast cancer Mona JeffreysSchool of Social and Community Medicine
2. Breast cancerMost common cancer in women in UKAffects approximately 50,000 women in UK each year85.1% of patients survive for five years or more (diagnosed 2005-2009)
3. Breast cancer incidencehttp://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/incidence
4. (Un)modifiable risk factorsAgeBRCA genes (family history)Breast densityBenign breast diseaseBirthweight, growth, height
5. Modifiable risk factorsReproductive factorsNulliparity / late age at first birth, early menarche, late menopause, breastfeedingExogenous oestrogens (OC, HRT)ShiftworkDietSaturated fat, phyto-oestrogens, fibreLifestyleBody weight, alcohol, physical activity, smoking
6. Breast cancer survivalhttp://www.cancerresearchuk.org/cancer-info/cancerstats/types/breast/survival/
7. Relative survivalSurvival “adjusted for” background mortality (excess mortality “due” to cancer)Avoids need for cause of deathObserved : expected survival ratioCompares “observed” survival in the cancer population to “expected” survival in general population
8. Relative survival (cont’d)Life-table methods (census)May not be valid when “observed” and “expected” groups have a different underlying expected mortalityCompare ethnic groupsCohort study with low response rate
9. Lifestyle determinants of survival
10. Lifestyle determinants of survivalGood evidence of lower survival in overweight women
11. Obesity and all cause mortalityProtani, BCRT 2010
12. Obesity and breast-cancer specific mortalityProtani, BCRT 2010
13. But is it all confounding?Women’s Intervention Nutrition StudyRCT of 2437 women, aged 43-79Early stage breast cancerIntervention: dietary fat reductionAssociated 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)
14. But is it all confounding?Women’s Healthy Eating and LivingRCT of 3088 women, aged 18-70Early stage breast cancerIntervention: High F&V, fibre and low fat No change in body weight or energy intakeNo 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)
15. Physical activity and breast cancer outcomesPatterson 2010, http://dx.doi.org/10.1016/j.maturitas.2010.01.004
16. Diet and breast cancer outcomesPatterson 2010, http://dx.doi.org/10.1016/j.maturitas.2010.01.004
17. Diet and breast cancer outcomes (cont’d)Patterson 2010, http://dx.doi.org/10.1016/j.maturitas.2010.01.004
18. New Zealand Breast Cancer StudyNationwide multi-ethnic, age- and ethnicity-matched population-based case-control study Over-sampling of Māori and Pacific women
19. MethodsCases identified from Cancer RegistryApril 2006 to April 2007Māori and Pacific cases to April 2008Controls from Electoral RollGeneralMāoriAdditional methods for Pacific controlsGP and community-based
20. Response rates (cases)1,799 cases302 (81%) Māori,70 (46%) Pacific, 1,427 (78%) non-Māori /non-Pacific
21. ExposuresBMI and WHRSmokingAlcoholPhysical activityDietServings of F&V, meat (red/white), fish, milk, cream, cheese
22. Timing of exposureLifetime“In the last year, on average...”Within 1 yearAfter 1 yearNumber (%)1,237 (71.5%)492 (28.5%)Median7.9 months22.3 monthsRange4 to 12 months12 to 39 months
23. Ascertainment of outcomeLinked to death registerCovers all of New ZealandRequires ethical approvalCensored at 28/02/2009Not valid for Pacific women“Going home to die”Informed of date of death but not causeAll cause mortality
24. Statistical methodsKaplan Meier curvesLog rank testsCox regressionFollowed from time of diagnosis to dead / censoringAdjusted for age at diagnosis, menopausal status, interview method, extent of disease at diagnosis (stage)
25. Basic resultsMāorinMnPTotal3021,427Deaths21 (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%)
26. Follow-up by ethnicityLog rank testP=0.56
27. Effect of BMI on survivalLog rank testP=0.21
28. Effect of BMI on survivalBMI (kg/m2)<2525 to 30>=30Adjusted*1.000.79 (0.50 to 1.24)0.73 (0.44 to 1.21)Pre-diagnostic1.000.86 (0.52 to 1.44)0.87 (0.49 to 1.54)Post-diagnostic1.000.49 (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
29. Effect of WHR on survivalLog rank testP=0.085
30. Effect of WHR on survivalWaist – hip ratioTertile 1Tertile 2Tertile 3Adjusted*1.001.20 (0.74 to 1.97)1.35 (0.82 to 2.22)Pre-diagnostic1.001.13 (0.65 to 1.95)1.48 (0.86 to 2.56)Post-diagnostic1.001.74 (0.53 to 5.73)1.13 (0.32 to 4.06)* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
31. Effect of alcohol on survival
32. Effect of alcohol on survivalNewcomb, JCO 2013
33. Effect of alcohol on survivalNewcomb, JCO 2013
34. Measurement of alcoholHow 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)
35. Alcohol frequency and amountAlcohol frequencyNever <=1/mthUp to 1/wk2-3/wk4+/wkAlcohol amountNone 33400001-2 drinks03542212092573-4 drinks0205062615-6 drinks0161517177-9 drinks01033810 or more08893Nil, slight, moderate, heavyUsed “slight” as the reference group
36. Effect of alcohol on survivalLog rank testP=0.14
37. Effect of alcohol on survival: overallAlcohol intakeNoneSlightModerateHeavyAdjusted*0.95 (0.57 to 1.58)1.000.93 (0.58 to 1.49)1.96 (0.98 to 3.94)Pre-diagnostic 0.79 (0.43 to 1.49)1.000.94 (0.56 to 1.57)1.39 (0.57 to 3.34)Post-diagnostic1.61 (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 disease
38. Effect of alcohol on survival: frequencyAlcohol intake (frequency)Never≤1/mthUp to 1/wk2+/wkAdjusted*1.08(0.61 to 1.90)1.001.49(0.82 to 2.72)1.18(0.70 to 1.98)Adjusted**1.19(0.66 to 2.16)1.001.63(0.86 to 3.09)1.26(0.73 to 2.19)Pre-diagnostic** 0.82 (0.41 to 1.64)1.001.05(0.50 to 2.21)0.95(0.52 to 1.71)Post-diagnostic**4.88(1.22 to 19.61)1.008.25(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
39. Effect of alcohol on survival: amountAlcohol intake (drinks per day)None1-23-45-67+Adjusted*0.98(0.61 to 1.58)1.000.97(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)1.000.93(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)1.001.06(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)1.000.54(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
40. SmokingHave you ever smoked, now or in the past?Are you a current smoker?Categorised into never, current, ex-smokers
41. Effect of smoking on survivalLog rank testP=0.66
42. Effect of smoking on survivalSmokingNever smokedEx-smokersCurrent smokersAdjusted*1.001.05 (0.69 to 1.58)1.43 (0.76 to 2.68)Pre-diagnostic1.000.94 (0.59 to 1.50)1.36 (0.63 to 2.93)Post-diagnostic1.001.95 (0.70 to 5.41)2.31 (0.65 to 8.28)* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
43. Physical activityMeasured using Godin questionnaireFrequency of mild, moderate and strenuousAnalysed in quartilesLowest quartile designated as “sedentary”
44. Effect of physical activity on survivalLog rank testP=0.146
45. * Adjusted for age, menopausal status, type of interview, ethnicity and extent of diseaseEffect of physical activity on survivalPhysical activityActiveSedentaryAdjusted*1.001.12 (0.74 to 1.69)Pre-diagnostic1.000.93 (0.57 to 1.52)Post-diagnostic1.002.03 (0.90 to 4.60)
46. Fruit and vegetable intakeHow many servings of vegetables (excluding potatoes) did you usually eat each week?How many servings of fruit did you usually eat each week?
47. Effect offruit and vegetable intake on survivalFruit intake(>14 servings per week)Vegetable intake(>21 servings per week)NoYesNoYesAdjusted*1.001.42 (0.96 to 2.10)1.001.41 (0.91 to 2.19)Pre-diagnostic1.001.43 (0.92 to 2.22)1.001.39 (0.84 to 2.29)Post-diagnostic1.001.27 (0.54 to 3.00)1.001.44 (0.55 to 3.73)* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
48. SummarySuggestion of poorer survival in women who wereHad lower BMI, but higher WHRNever and heavy alcohol drinkersSedentaryNo clear relationship withF&V intakeSmoking
49. Other dietary measuresNo clear relationship with intake of MilkCreamCheeseMeat (red/white)Fish
50. Dairy intake and cancer survival
51. Dairy intake and cancer survivalKroenke, JNCI 2013
52. Limitations of NZ studyPoor measurement of some exposuresParticularly dietary measuresWhat time frame are women actually reporting on?
53. Effect of childhoodfruit and vegetable intake on survivalFruit intake(days/week)Vegetable intake(days/week)<=45+<=45+Adjusted*1.001.09 (0.74 to 1.62)1.000.48 (0.28 to 0.83)* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
54. Effect of childhoodfruit and vegetable intake on survivalFruit intake(days/week)Vegetable intake(days/week)<=45+<=45+Adjusted*1.001.09 (0.74 to 1.62)1.000.48 (0.28 to 0.83)Pre-diagnostic1.001.39 (0.87 to 2.19)1.000.44 (0.24 to 0.82)Post-diagnostic1.000.47 (0.20 to 1.08)1.000.61 (0.20 to 1.84)* Adjusted for age, menopausal status, type of interview, ethnicity and extent of disease
55. Determinants of high F&V reportingFruit 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
56. Determinants of high F&V reportingFruit 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 year1.15 (0.91 to 1.45)1.50 (1.16 to 1.95)Unrelated: area deprivation, childhood SEP, age, menopausal status, extent of disease
57. Limitations of NZ studyPoor measurement of some exposuresParticularly dietary measuresWhat time frame are women actually reporting on?Pre- and post-diagnostic comparisons are not of the same womenIdeally have a measure of changeSurvivor biasConditional survivalLimited statistical power for some analyses
58. Where next?Re-analysis with longer follow-upPhysical activity intervention trialacceptability of intervention and randomisationConsider weight loss interventioneffect on lean body mass
59. AcknowledgementsCo-PIs: Lis Ellison-Loschmann, Fiona McKenzie, Riz FirestoneCo-Investigators: Neil Pearce, Michelle Gray, Ate Moala, Soo ChengFunders: New Zealand Lottery Grants BoardMassey University Research FundHealth Research Council of New ZealandCancer Society of New Zealand