Anne McTiernan, MD, PhDFred Hutchinson Cancer Research Center, Seattle, WA, USAWCRF/AICR CUP Panel

The WCRF/AICR Continuous Update Project – Systematic Reviews on Nutrition, Physical Activity & Health Outcomes in Cancer Survivors

ICNSeptember 2013

Recognition World Cancer Research Fund International

Dr. Rachel Thompson, PhD PHNutr, Professor Martin Wiseman, FRCP FRCPath, & colleagues

American Institute for Cancer Research, USA Dr. Susan Higginbotham, PhD

Imperial College London Dr. Teresa Norat, PhD & colleagues

Continuous Update Project Panel International scientific experts

Why Study Cancer Survivors? U.S. National Cancer Institute: In cancer, a

person is considered to be a survivor from the time of diagnosis until the end of life

~ 28 million cancer survivors worldwide Growing evidence of associations between

nutrition, weight, physical activity & cancer prognosis

Role of lifestyle may differ for cancer prognosis vs. prevention, and may differ by cancer type

‘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)

Rationale for Focus on Breast Cancer

Globally, 1.38 million new breast cancer cases diagnosed in 2008 (23% of all cancers)

Ranks second overall (10.9% of all cancers)

Most available data on nutrition and cancer survivors is for breast cancer

Additional cancer sites will be studied

Global Health Statistics: Breast Cancer

CA: A Cancer Journal for Clinicians 2011;61(2):69-90WHO IARC GLOBOSCAN http://globocan.iarc.fr/factsheet.asp

Types of Studies

Most studies with mortality endpoints are observational

Greater weight placed on randomized clinical trials vs. follow-up studies

Criteria for Study Inclusion

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

Breast Cancer Survivors Included

Pre-menopausal women Post-menopausal women Incident in-situ breast cancer Incident invasive breast cancer

Exposures Included Specific foods Micro- and macro-nutrients Dietary patterns Alcohol Overweight, obesity, underweight, weight

change Body composition Dietary supplements Physical activity

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

Outcomes Included

Total mortality Breast cancer specific mortality Second primary breast cancer Other cause-specific mortality, i.e.

cardiovascular

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

Issues Relevant to Survivor Research

Confounding effects of: Treatment types, efficacies, adverse effects Stage of disease Comorbidities Type of cancer

Methodological: Determining cause of death Determining and classifying recurrence Screening for second primary breast cancer Increasing length of survival

Literature search(New search for CUP)

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 criteria85 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

Example: Alcohol Alcohol use associated with increased risk

of breast cancer development Unclear if use associated with survival Most data from pre-diagnosis or beyond

12-months post-diagnosis Data from self-report only Little information on specific alcohol types Little information on cancer treatments Major cultural/geographic variation in use

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. Low

2650 0.93 (0.82-1.06) 1329 1.18 (0.81-1.72) - -

Before : Per 1 drink/week

26761.00 (0.99-1.00)

12961.00 (0.97-1.02) - -

After diagnosis:High vs. Low

38270.89 (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)

Example: Body Mass Index (BMI) Increased BMI associated with risk for

postmenopausal breast cancer, but not for premenopausal breast cancer

Measured or self-reported height & weight Data from clinical series, trials, &

epidemiological studies Most data from 12-month period after

diagnosis, and from before diagnosis

Summary: Before diagnosis- BMI summary

Total mortality Breast cancer mortalitySecond primary breast cancer

N deaths

RR (95%CI)N deaths

RR (95%CI)N events

RR (95%CI)

High vs. Low 8318 1.41 (1.29-1.54) 9854 1.34 (1.23-1.46) 701 1.43 (0.87-2.34)

Underweight vs. normal weight

4944 1.10 (0.92-1.31) 4479 1.02 (0.85-1.21) - -

Per 5 kg/m2 6261 1.17 (1.13-1.21) 6600 1.17 (1.11-1.24) 701 1.21 (1.04-1.40)

Premenopause 644 1.25 (1.10-1.43) 1350 1.06 (0.85-1.32) - -

Postmenopause 1103 1.16 (1.01-1.34) 2866 1.15 (1.05-1.25) - -

Summary: Around diagnosis- BMI summary 1

Total mortality Breast cancer mortalitySecond primary breast cancer

N deaths

RR (95%CI)N deaths

RR (95%CI)N events

RR (95%CI)

High vs. Low BMI

16925 1.27 (1.16-1.38) 10063 1.36 (1.23-1.50) 3478 1.30 (1.14-1.48)

Premenopause 4604 1.28 (1.16-1.42) 586 0.96 (0.45-2.06) - -

Postmenopause 4614 1.13 (1.03-1.23) 1067 1.57 (1.31-1.89) - -

Underweight vs. normal weight

2598 1.23 (0.93-1.63) 1455 1.52 (1.26-1.84) - -

Per 5 kg/m2 5875 1.11 (1.06-1.17) 1918 1.18 (1.11-1.25) 3186 1.13 (1.06-1.21)

Summary: After diagnosis – BMI summary

Total mortality Breast cancer mortalitySecond primary breast cancer

N deaths

RR (95%CI)N deaths

RR (95%CI)N events

RR (95%CI)

High vs. Low 2289 1.21 (1.06-1.38)2 studies

Both risk, 1 significantNo studies

Underweight vs. normal weight

1361 1.29 (1.02-1.63)

Per 5 kg/m2 1703 1.08 (1.01-1.15)4, 0%, p=0.52

Global Implications

Global Prevalence of Overweight & Obesity in Women

Newly developed criteria specific for cancer survivors for judging evidence

Recommendations for breast cancer survivors

To reduce mortality, prevent further primary cancers, and other diseases

Future considerations

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 Systematic literature review identifies

patterns of associations for nutrient-related factors & breast cancer survival