The document discusses the role of omega-3 fatty acids in health and breast cancer prevention, highlighting the increase in breast cancer mortality globally. It presents research findings indicating a potential causal link between omega-3 fatty acids and reduced breast cancer risk, with variations in potency between different sources of omega-3. The key findings suggest that lifelong exposure to omega-3 fatty acids may positively influence mammary tumor development and outcomes.

1. Omega-3 Fats for Health and
Breast Cancer Prevention
David W.L. Ma, Ph.D.
Professor
Department of Human Health & Nutritional
Sciences
University of Guelph, Canada

3. Breast Cancer Statistics
• Globally, cancer is the 2nd leading cause of
death in 2015 after cardiovascular disease
contributing to 8.8 and 18 million deaths,
respectively1.
• Among female cancers, breast cancer is a
leading cause of death worldwide, which
increased 21% from 2005 to 2015 or 440,000
to 534,000 deaths1.
Lancet 2016; 388: 1545–602

4. By 2032,
25 million
new cases
each year
• Smoking
• Diet
• Obesity
• Physical
Inactivity

5. “30-40% of
cancer is
preventable by
food and
nutrition”

6. Prevalence of Cancer, last 25 years
Canadian Cancer Statistics Advisory in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of
Canada. Canadian Cancer Statistics: A 2022 special report on cancer prevalence. Toronto, ON: Canadian Cancer Society; 2022. Available at:
cancer.ca/Canadian-Cancer-Statistics-2022-EN

8. 1. Diets high in sodium,
2. low in vegetables,
3. low in fruit,
4. low in whole grains,
5. low in nuts and seeds
6. low in seafood omega-3.

9. Research questions in my lab
1. Is there a causal link between omega-3 fatty acids
and breast cancer?
2. What is the role of individual omega-3 fatty acids?

10. Dietary Fat and Cancer
Toxicological Sciences, 1999; 52 (Suppl) 127-146

11. Unsaturated
Fatty Acids
Monounsaturated Fatty Acids
(MUFA)
Polyunsaturated Fatty Acids
(PUFA)
Omega-6
Omega-3
Linoleic
Acid (LA)
Alpha linolenic
Acid (ALA)
Arachidonic
Acid (AA)
Eicosapentaenoic
Acid (EPA)
Docosahexaenoic
Acid (DHA)
Saturated Fatty Acids
(SAFA)
Oleic
Acid
Palmitic
Acid
Stearic
Acid
Types of Dietary Fats
Omega-9
Trans Fatty Acids
(TFA)
Partially Hydrogenated
Natural Occurring Trans
Elaidic
Acid
Vaccenic
Acid
Conjugated
Linoleic Acid (CLA)

12. Omega-3 Fatty Acids
α-Linolenic Acid, 18:3n3 (ALA)
Eicosapentaenoic Acid, 20:5n3 (EPA)
Docosahexaenoic Acid, 22:6n3 (DHA)

13. Is there a causal link between
lifelong n-3 PUFA exposure and
mammary tumour
development?

14. Fat-1 Mouse: Genetic Model
for Studying N-3 PUFA
• Endogenous n-3 PUFA production
• Control for dietary confounders
n3 Desat.
n6 n6
n6 n3

15. Her2 Breast Cancer Model
• Mouse Mammary Tumour Virus–neu-ndl-YD5
(MMTV-neu-ndl-YD5)
– Aggressive mammary tumour model
– HER2/neu over-expression causes increased cell proliferation
• Her2 or neu oncogene
– Over-expression results in tumourigenesis
– 25% of human breast cancer

16. Experimental Design
MMTV fat-1
MMTV MMTV / fat-1
fat-1
WT
0 3 20
Tumour Development

17. Experimental Diets
Genetic Arm
• n-6 PUFA Diet, 10% Safflower Oil
• fed to MMTV and MMTVxfat-1 mice
Dietary Arm
• n-3 PUFA Diet, 3% menhaden fish oil + 7% Safflower Oil
• fed to MMTV mice

18. Tumour Growth by Multiplicity
* Significantly different by repeated measures analysis as compared to MMTV control group
*
*

19. Tumour Growth by Volume
*
*
* Significantly different by repeated measures analysis as compared to MMTV control group

20. Is More Better?

21. Dose Dependent Effect of n-3
PUFA on Tumour Free Status

22. More n-3 PUFA leads to smaller tumours

23. 5% reduction in breast
cancer risk for each
100mg EPA+DHA

24. Is Plant or Fish based
n-3 PUFA Better?

25. N-3 PUFA reduced TEB structures at 6
weeks
(n= 12-16 per diet)
0
5
10
15
20
25
Average
number
of
TEBs
a
a
b b
0
0.1
0.2
0.3
0.4
0.5
Average
density
of
TEBs
(TEB/mm
2
)
a
a
b b
10% Safflower 3% Flaxseed 10% Flaxseed 3% Menhaden

26. N-3 PUFA increased tumor-free mice
(n=12 per diet)
0
10
20
30
40
50
60
70
80
90
100
110
1 74 79 84 89 94 99 104 109 114 119 124 129 134 139
%
of
Mice
Tumor
Free
Age of Tumor Onset (day)
Threshold dose 50 (TD50)
b
b
a
a
10% safflower
3% flaxseed
10% flaxseed
3% menhaden

27. N-3 PUFA inhibited tumor development
Time (week)
10% Safflower
3% Flaxseed
10% Flaxseed
3% Menhaden
a
b
c
d
0
1
2
3
4
5
6
7
8
1011121314151617181920
Average
Number
of
tumors
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
1011121314151617181920
Average
tumor
volume
(mm
3
)
a
b
c
c
Average Tumor Volume Average Tumor Multiplicity
Time (week) (n= 12 per diet)

28. Is Plant or Fish Based
n-3 PUFA better?
Why does it matter?
Majority of n-3 PUFA in N. American diet is from ALA
What is relative potency?
Between 1/3 to 1/8

29. In Summary: Key Findings to Date
• Flaxseed oil is 1/3 as potent as menhaden oil;
ALA is 1/8 as potent as EPA and DHA
• Dose-response relationship between ALA
and BC
• Lifelong exposure to n-3 PUFA influences MG
development and mitigate tumor outcomes

30. Canadian Cancer Survivor Network
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