Bringing life course epidemiology to understanding etiology and implications for timing of prevention . Studies cited in slides, but also motivated by much of my resesrch summarized here: Colditz GA, Frazier AL 1995 CEBP Models of breast cancer show risk is set by events of early life: prevention efforts must shift focus Terry MB, Colditz GA 2023 Cold Spring Harb Perspective Med Colditz G, AND Bohlke K 2015 NPJ Breast Cancer Colditz, Bohlke, Berkey 2014 Breast Ca Res Treatment

1. A lifecourse approach to cancer:
Breast cancer prevention across the
lifecourse
Graham A. Colditz, MD, DrPH
Niess-Gain Professor
Department of Surgery
Division of Public Health Sciences
University of Zurich, March 21, 2023

2. Department of Surgery
Division of Public Health Sciences
Disclosure Information
I have no financial relationships to disclose
I will not discuss off-label use or investigational use
of drugs or devices in my presentation
Slides available online slideshare.net/grahamcolditz

3. Department of Surgery
Division of Public Health Sciences
Overview
I. Burden – growing & global
II. Preventable – risk is modifiable
III.Drivers of breast cancer
IV. Focusing breast cancer prevention
V. Steps we can take now given lifecourse insights

4. Department of Surgery
Division of Public Health Sciences
Global cancer burden, 2018
17 million new cases of cancer
diagnosed
8.8M men; 8.2M women
2.1 Million new cases of breast cancer
25.4% of all cancer diagnosed in
women https://www.who.int/cancer/PRGlobocanFinal.pdf

5. Department of Surgery
Division of Public Health Sciences
Perspective on 2018 cancer new
cases
1 in 4 cancers in women = breast cancer
Under age 50
1 in 3 cancers diagnosed in women world wide is breast cancer
2,088,849 breast cancers diagnosed
2,093,876 lung cancers (men and women
combined)
http://gco.iarc.fr/today/home

6. Department of Surgery
Division of Public Health Sciences
Breast cancer is preventable

7. Department of Surgery
Division of Public Health Sciences
Evidence that breast cancer is
preventable
Migrant studies
Non-US lifestyle,
Substantial changes in risk over generations, but
disentangling the complexity of lifestyle changes
makes interpretation difficult
Within-country changes
Remove E&P HT, Korea rapid increase, China, etc.
Cancer burden
Barriers:
1. Skepticism
Drivers
Focusing
prevention
Steps we can
take now
Breast Cancer
Prevention

8. Department of Surgery
Division of Public Health Sciences
Lei Fan , et al. Breast cancer in China
The Lancet Oncology, Volume 15, Issue 7, 2014, e279 - e289
Breast Cancer
Prevention
Cancer burden
Barriers
1. Skepticism
Drivers
Implications
for prevention
Steps we can
take now
Within-country change: Incidence
of breast cancer, China, 2009.
Urban
Rural

9. Department of Surgery
Division of Public Health Sciences
300,000 women in the China
Kadoorie Study
Breast Cancer
Prevention
Cancer
burden
Barriers
Drivers
Focusing
prevention
Steps we
can take
now
Lewington IJE 2014

10. Department of Surgery
Division of Public Health Sciences
Drivers
What is driving risk?
When is it acting?
• Colditz GA, Frazier AL 1995 CEBP Models of breast cancer show risk is set
by events of early life: prevention efforts must shift focus
• Terry MB, Colditz GA 2023 Cold Spring Harb Perspective Med
• Colditz G, AND Bohlke K 2015 NPJ Breast Cancer
• Colditz, Bohlke, Berkey 2014 Breast Ca Res Treatment

11. Department of Surgery
Division of Public Health Sciences
Life-course development of
risk accumulation
• Long-term effects of early radiation
• Menopause – cessation of menstrual
cycles leads to slower risk accumulation
• Menopause tells us hormones or
accumulation through premenopausal
years must be important
• Menarche and height point to early life as
important
Breast Cancer
Prevention
Cancer burden
Barriers
1. Skepticism
2. Short-term
3. Timing
Drivers
Focusing
prevention
Steps we can
take now

12. Department of Surgery
Division of Public Health Sciences
Long-term effects of radiation in
early life
Land et al. Radiation Research 2003
Atomic bomb
survivors,
70,165
40 year follow-up
1059 cases

13. Department of Surgery
Division of Public Health Sciences
Pike model
• Based on epidemiologic
data postulated breast
tissue age varied
according to reproductive
risk factors
• “To accommodate the
higher incidence with late
first birth, we add a
constant “b” representing
an increase in risk with
FFTP
Pike et al Nature 1983

14. Department of Surgery
Division of Public Health Sciences
Accumulating risk, multiple birth
model
Rosner, Colditz, Willett, Am J Epidemiology 1994;139:826
Rate
of
tissue
aging
menarche birth birth birth menopause

15. Department of Surgery
Division of Public Health Sciences
Accumulating risk, multiple birth
model
Rosner, Colditz, Willett Am J Epidemiology 1994;139:826
9% /yr
2.5% /yr
Menarche 1st birth Menopause Current age
Rate
of
tissue
aging

16. Department of Surgery
Division of Public Health Sciences
When, where, what to do?
• <50 years
• 50 to 74
• 75+

17. Department of Surgery
Division of Public Health Sciences
Drivers of breast cancer
• Progression through premalignant lesions as
risk accumulates
• Faster rise in risk before menopause than
after
• Hormonal cycling during premenopausal
years
• Rapid childhood growth in height
• Diet and physical activity
Colditz & Bohlke npj Breast Cancer 2015

18. Department of Surgery
Division of Public Health Sciences
Model of breast cancer development
Wellings-Jensen Model (JNCI 55:231, 1975)
Adapted from Allred
Time (decades)
TDLU
ADH DCIS IBC
­Growth
CCH
Ds Adhesion
& Polarity
­Diversity
Invasion

19. Surrogates – soy, fiber, fruit and vegetables

20. Department of Surgery
Division of Public Health Sciences
Adolescent fiber & proliferative BBD:
NHSII
Su et al. Cancer Causes Control 2010

21. Department of Surgery
Division of Public Health Sciences
• Strongest protective effect seen for sustained
activity from ages 13 through 22 to prevent
premenopausal breast cancer
• Increasing activity decreasing breast cancer risk

22. Department of Surgery
Division of Public Health Sciences
Premenopausal
Breast Cancer
0.86 (0.76-0.97)
ER/PR Positive
Breast Cancer
0.80 (0.66-0.98)
Postmenopausal
Breast Cancer
0.91 (0.84-0.98)
ER/PR Negative
Breast Cancer
0.68 (0.55-0.83)
Plant-Based Diet and Breast Cancer Risk
Xiao Y et al. Breast Cancer Research 2019

23. Department of Surgery
Division of Public Health Sciences

24. Department of Surgery
Division of Public Health Sciences
Summary of evidence
• Avoiding alcohol lowers risk
• Higher fruit, veggies, fiber, and nuts lower risk
• Exercise from adolescence on lowers risk
• Avoiding/reducing radiation
• Non – modifiable – Family history
• Even with high-risk family genetic factors, risk is
still modifiable.

25. Department of Surgery
Division of Public Health Sciences
Steps we can take now to prevent breast
cancer, in context of lifecourse insights
Target prevention early in life
• Eat mostly a plant-based diet
• Limit alcohol before first pregnancy, zero is best
• Increase and maintain physical activity
Work globally and locally
Refine messaging and social strategy

26. Department of Surgery
Division of Public Health Sciences
Breast cancer prevention imperative
Timing matters
• To maximize benefits we must focus on biologically
relevant periods
• Identify lifestyle factors that limit the impact of drivers
• Tap potential benefit from childhood and adolescent
plant diet and physical activity
§ What intermediate marker can we measure?
Must identify strategies to counter adverse effect of
alcohol

27. Department of Surgery
Division of Public Health Sciences
Messages for 16 to 30 to 50 to 70
year old women and their families
and communities
1) Go big with plant based foods – fruits,
vegetables, nuts, and whole grains
2) Think before you drink – zero is best
3) Put on those Dancing – and Walking and
Running and Cycling shoes
4) Don’t obsess – but watch your weight

28. Department of Surgery
Division of Public Health Sciences