The document summarizes a randomized controlled trial that compares intermittent energy restriction (IER) to continuous energy restriction (CER) in women receiving chemotherapy for early breast cancer. The trial aims to test if IER is feasible for women on chemotherapy and to compare the two diets' effects on weight changes, body composition, chemotherapy toxicity, and blood biomarkers. Over 470 women were screened for eligibility, with 172 women enrolled and randomly assigned to receive individual counseling and support for either the IER or CER diet during their 4.5-6 months of chemotherapy. Outcomes will be assessed after chemotherapy completion to analyze differences between the diet groups.

1. The B-AHEAD 2 Trial
Randomised controlled trial of intermittent
versus continuous energy restriction during
adjuvant chemotherapy:
Dr Michelle Harvie
Research Dietitian
The Nightingale and Prevent Breast Cancer Centre
University Hospital of South Manchester

2. Background
• Excess weight at diagnosis and weight gain after
diagnosis increase risk of recurrence and mortality
(Chan et al Ann Oncology 2014
• Daily energy restriction and exercise is only partially
effective for weight control in pts receiving
chemotherapy for early breast cancer (-0.8Kg)
(Harvie et al B – AHEAD study)
• We have reported greater weight loss with intermittent
vs. standard daily energy restriction in healthy
overweight / obese women
(Harvie et al Br J Cancer 2013)
• Animal studies and case series suggest intermittent
energy restriction reduce chemotherapy toxicity
(Brandhorst & Metabolism & Cancer Springer 2016)

3. Aim
•To test whether IER is feasible amongst women receiving
chemotherapy for early breast cancer.
•To compare intermittent energy restriction vs. continuous energy
restriction for :
Primary endpoints
• Changes in weight, body fat and fat free mass (DXA)
• Chemotherapy toxicity:
-Self reported CTCAE scores, dose reduction, dose delay, hospitalisation,
-Blood toxicity biomarkers; serum CK18 (epithelial toxicity) & plasma FLT 3 ligand
(myelosuppression) (n = 55)

4. “Research findings may be coupled with
suggestions and guesses to build up
concepts which by pyramided repetition
become accepted”
Tannenbaum & Silverstone 1953
Early intermittent fasting researchers
Dept of Cancer research Michael Reese Hospital Chicago , USA

5. The IER and CER diets
70% of subjects
Overweight / obese
Aim to lose weight
Overall 25% energy
restriction
IER 2 days low carb, 50-70% ER/wk 650-800kcal
+5 days week Mediterranean diet
CER 25% energy restricted
Mediterranean diet 7 days /week
30% of subjects
Normal weight
Aim to maintain weight i.e.
prevent wt gain
No energy restriction
IER 2 days low carb, 50-70% ER/wk 650-800kcal
+5 days week Mediterranean diet cal
CER Mediterranean diet 7 days /week to meet
estimated energy requirements

6. Outcomes assessed 3 weeks after final chemotherapy
n = 172
Scheduled to receive adjuvant or neoadjuvant chemotherapy
• 2 day / week IER (& physical activity)
• Individual face to face advice
• Telephone support (alternate weeks)
• Mailings (alternate weeks)
IER n=86 CER n=86
• Continuous energy restricted diet (&
physical activity)
• Individual face to face advice
• Telephone support (alternate weeks)
• Mailings (alternate weeks)
Study design
4.5–6monthsofchemotherapy

7. Inclusion criteria
• Scheduled to have standard adjuvant or neoadjuvant chemotherapy
• Breast cancer stage I–III
• Any age >18 years
• BMI>19 kg / m2. We aim to prevent weight gain (normal wt) & promote wt
loss (overweight / obese)
• Resident within Greater Manchester or Cheshire area
• Clear routine staging CT scan (for patients scheduled to receive
neoadjuvant chemotherapy & patients with 4 or more axillary nodes)
Exclusion criteria
• Metastatic disease
• Had previous chemotherapy within the last 2 years
• Serious cardiovascular, respiratory, musculoskeletal, digestive or
psychiatric condition
• Medications affecting weight e.g. daily steroids (2-3 days with
chemotherapy ok)
• Diabetics on insulin or sulphonylureas as could cause hypoglycaemia on
2 day diet
• Already commenced current course of chemotherapy

8. Recruitment
Not eligible n = 192 (29%)
25% - Already started chemotherapy
19% - Co morbidities
7% - Metastatic disease
5% - Low BMI
6% - IDDM
7% - Language
31% - Other
470 eligible
Not want to join n = 298 (45%)
18% - Did not want extra appts
15% - Not interested
12% - Too anxious
9% - Travel issues
5% - Not want to diet during chemo
3% - Already eats healthily
1% - Not want to be randomised
27% - Unknown
36% uptake of eligible women (8-50% in the centres)
Number screened in 11 cancer centres
n = 662

9. Baseline characteristics
IER ( n = 86) CER (n = 86)
Age (years) 51.3(9.0) 52.6(10.1)
BMI (Kg/m2) 28.1(6.1) 28.4(6.1)
Overweight/ obese/ normal wt - % 69/ 31 71/ 29
Premenopausal % 56 55
Ethnicity, Caucasian-% 96 88
Grade Invasive 1/2/3 /DCIS -% 4/ 30/ 64/ 2 5 / 43 / 51/ 1
ER +/ER- % 31 / 69 33 / 67
Chemotherapy -%
FEC –docetaxel
FEC-paclitaxel
Other
59
13
28
56
13
31
Adjuvant / neoadjuvant % 93/ 7 93/ 7
Current smoker % 7 3.5
Mean (SD)

10. Retention to trial
Intermittent Continuous Withdrawn
2 1 Excluded after consent as not eligible
1 0 Developed mets during study
1 2 Too busy/Too many appts
6 3 Loss of contact
3 1 Not coping with chemo
2 2 Not tolerate diet
4 0 Other illness / feels too unwell
19 9 Total
22% 10% % Withdrawn
IER n = 86 CER n = 86
Calls received 7.6/10 7.5/10
% compliance with IER
2 days/ week during trial
All patients (n = 86)
Completers only
(n = 67)
57%
62%
N/A
Adherence

11. Conclusion
• Good uptake and retention show diet & exercise interventions
are feasible & welcomed amongst chemotherapy patients
• IER is feasible amongst chemotherapy patients
• Further analysis will inform the safety, harms of IER & CER i.e.
dose information, hospitalisation, quality of life & objective
blood markers of toxicity

12. Acknowledgements
Prevent Breast Cancer
Breast Cancer Research Trust
Our Trial Participants
FundingLifestyle 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
PI’s & research nurses in
recruiting centres