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Could managing obesity help cancer patients?
Michelle Harvie PhD SRD Research Dietitian
The Nightingale and Prevent Breast Cancer Centre University Hospital of South Manchester NHS Foundation Trust
Food Matters Live Wednesday 23rd November
Questions
How many cancer patients are obese?
Will managing weight: Stop cancer coming back / progressing ?
Reduce risks of CVD / diabetes & does this matter for cancer patients ?
Prevent second cancers?
Make cancer patients feel better?
Don’t pts lose weight anyway because of the cancer
treatments?
What research is being done? - our B-AHEAD breast
cancer trials
Current guidelines on weight
• General advice for cancer patients to be a healthy weight • Not advised for metastatic patients • Focus after active chemotherapy / radiotherapy
ASCO 2015 NHS/ Macmillan Cancer Support 2013
Are these guidelines evidence based?
World Cancer Research Fund
Excess weight increases risk of 14
cancers
1 Post-menopausal breast
2 Endometrial
3 Ovarian
4 Advanced prostate
5 Colorectal
6 Kidney
7 Pancreatic
IARC Working Group. N Engl J Med. 2016 25;375(8):794-8
8 Liver
9 Gallbladder
10 Gastric cardia
11 Oesophageal adenocarcinoma
12 Thyroid
13 Meningioma
14 Multiple myeloma
How many cancer patients are obese?
Cancer % with BMI > 30 Kg/ m2
Localised disease
Endometrial 39 - 47
Renal 42
Breast 23- 27
Colorectal 17 - 37
Ovarian cancer 12- 15
Prostate 30 – 40
Metastatic
Colorectal 12
Breast 22-27
Renehan et al in press JCO
Questions
Will managing weight stop cancer coming back / progressing ?
Obesity & outcome:Meta-analyses
No. of studies
Cancer - mortality (obese vs. normal weight)
Breast cancer
Kwan et al. 2012 4 cohorts BMI > 40 : 40% increase
Cecchini et al. 2016
4 adjuvant RCTs: ER positive: 30% increase
Colorectal
Sinicrope et al. 2014
21 adjuvant RCTs 11% increase
Prostate
Cao & Ma 2011 12 (mixed study types)
20% increase per 5 kg/m2
Obesity & outcome:Meta-analyses
No. of studies
Cancer - mortality (obese versus normal weight)
Endometrial cancer
Arem & Irwin 2013 12 (mixed study types)
Equivocal evidence 4 studies showed association; 8 found
no association
Ovarian cancer
Bae et al. 2016 17 (mixed study types)
Equivocal evidence
Renal cancer
Bagheri 2016 8 (mixed study types)
Equivocal evidence 28% increase per 5 kg/m2
but increased overall mortality
Heavier patients have worse prognostic tumours at diagnosis
Normal
weight
Overweight Obese
Tumour size 20mm 24mm 26mm
Grade 3 59% 64% 64%
Node positive 49% 54% 55%
Triple negative 21% 23% 27%
Copson ER Ann Oncol. 2015 26(1):101-12
2596 premenopausal breast cancer patients
Chemotherapy dose-capping
Authors,
country
Cancer Normal
weight
Over-
weight
Obese
Griggs
2005, USA Breast
Pittsburgh
Cohort study
9% 11% 20%
Chambers
2012, UK Colorectal FOCUS2 trial
12% 21% 60%
Au-Yeung
2014,
Australia
Ovarian Australian Ovarian
Cancer Study
39% 39% 67%
Relapse rates high if < 85% chemo dose & = no treatment Bonadonna G N Engl J Med.1995;332(14):901-6
30%
50%
Breast cancer: CMF vs. no chemotherapy
One randomised trial of low fat diet, weight loss & outcome – WINS (n = 2437)
Weight change at 1 year -2.7 low fat vs + 0.7 control
5 year follow up 24% reduction in recurrence or new contralateral breast cancer
Chlebowski et al 2006 JNCI 98: 24
15 year follow up Overall mortality ER-ve : 36% reduction Triple –ve : 56% reduction
Chlebowski et al 2014 San Antonio Breast Conference
Ongoing RCTs of weight control in early BC patients
Trial Trial centre Intervention Population N Results expected
SUCCESS-C
Hauner Germany
24 months Diet and exercise 5-10% weight loss
Overweight. After adjuvant chemotherapy
3547 2016 ?
DIANA-5 Berrino Italy
WCRF recommendations 5 year FUP
Any weight. Within 5 years of diagnosis
1208 2016 ?
NCKMA32 Goodwin International
5 years Metformin 850mg bd
Any weight. After adjuvant chemotherapy
3582 2020
Breast Cancer Weight Loss Study (BWEL)
Ligebel USA & Canada
Weight loss (diet and exercise)
BMI ≥27 kg/m2 Within 12 months of diagnosis
3136 2030
We are hoping to set up a UK weight loss & outcome trial
Questions
Will managing weight reduce risks of CVD / diabetes & does this matter for cancer patients ?
Cardiovascular risk: Breast cancer patients
Cardiotoxicity • Anthracyclines • HER-2 inhibitors • Radiotherapy
Increase thrombotic events • Hormonal therapies eg. tamoxifen • Antiangiogenic drugs
Bardia A Breast Cancer Res Treat.2012;131(3):907-14.
N = 415 post menopausal early BC pts 10 year risk of BC recurrence & CVD event
BC> CVD 20%
BC=CVD 43%
CVD>BC 37%
Obesity increases non-cancer
deaths
Cancer Risk of non-cancer death Obese vs. normal weight patients
Kwan et al 2012
Breast n = 14,948
BMI 35-40 40% increase BMI >40 3 x risk
Campbell et al 2012
Colorectal n = 2303
Per 5kg / m2 28% increase
Questions
Will managing weight prevent second cancers?
Obesity increases second cancers
amongst cancer patients
Cancer patients
Type of secondary cancer
Druesne-Pecollo 2012
Breast 8 studies n= 27,230
Contralateral breast 37% increase Endometrial 96% increase Colorectal 89% increase
Gibson 2014 Colorectal 5 studies
n = 11,598
Any weight related cancer 47% increase Endometrial cancer 341% increase
Questions
Will managing weight make cancer patients feel better?
Weight loss programmes increase well-being in the short term
Outcome Baseline 6 M 12 M 24 M
Vitality ( SF36)
Intervention 60.5 (1.36) 65.1 (1.20) 62.2 (1.25) 60.5 (1.28)
Control 60.5 (1.37) 62.4 (1.23) 61.0 (1.29) 63.2 (1.31)
p value <0.05 NS NS
BC symptom score
Intervention 1.99 (0.03) 1.89 (0.03) 2.01 (0.03) 1.99 (0.03)
Control 2.02 (0.03) 2.02 (0.03) 2.07 (0.03) 2.02 (0.03)
p value <0.05 NS NS
Depression(CES-D)
Intervention 9.9 (0.50) 11.4 (0.44) 11.9 (0.45) 11.8 (0.47)
Control 9.7 (0.50) 10.6 (0.44) 10.9 (0.47) 9.9 (0.47)
p value NS NS <0.05
Mean (SEM)
692 early breast cancer patients – 12 month programme
Demark – Wahnefried Breast Cancer Res Treat. 2015; 154(2): 329–337
Questions
Don’t pts lose weight anyway because of the cancer treatments?
86 early BC patients 15- 17 weeks of chemotherapy
Need to prevent weight gain during adjuvant chemotherapy for BC patients
Dieli-Conwright Cancer 2016;122(17):2646-53
Conclusions How many cancer patients are obese?
Significant problem
Will managing weight:
• Stop cancer coming back / progressing ?
Possibly breast, colorectal , prostate
• Reduce risks of CVD / diabetes & does this matter for cancer patients ?
Yes Yes for some cancers i.e. breast cancer
• Prevent second cancers?
Yes
• Make cancer patients feel better?
Yes if we can keep weight off
• Don’t pts lose weight anyway because of the cancer treatments?
No, need to prevent weight gain for breast & possibly prostate & colorectal cancer
Patient feedback …
“Gives women some control.”
“Helps overall self-esteem if you don’t put
weight on.”
“I was glad I was on the diet and actually
managed to lose weight!”
“It has been a great help to me and given me
something to focus on apart from the chemo.”
Acknowledgements
Prevent Breast Cancer
Breast Cancer Research Trust
Anticancer Fund
Our Trial Participants
Funding Lifestyle Research Team
Co-investigators Sacha Howell Tony Howell Anne Armstrong Nigel Bundred Lee Graves Mark Mattson Judy Adams Louise Gorman
Mary Pegington Nina Brogden Claire Lindsay Kath Sellers Grace Cooper Debbie McMullen Pam Coates Lesley Coates Cheryl Barlow Prevent BC Volunteers PIs & research nurses in recruiting centres
Lead Research Dietitian Dr Michelle Harvie