Download Tenth Anniversary of Initial Women`s Health

Tenth Anniversary of Initial Women’s
Health Initiative (WHI) Report
Richard Santen, MD
University of Virginia
12/2/11
Tenth Anniversary of Initial Women’s
Health Initiative (WHI) Report
• What have we learned?
• How should the public be informed?
• What should a post-menopausal woman do,
based on what we now know?
WHI
• First report 2002
• Two arms
– Placebo versus conjugated equine estrogen plus MPA
(E+P)
– Placebo versus conjugated equine estrogen alone (E)
• 80% reduction in menopausal hormone use over
the next five years
WHI 10 years later:
key conclusions after a decade of reflection
• Need to consider all information based on
excess risk and benefit and not relative risk
and benefit
• Only women just entering menopause are
candidates for menopausal hormone therapy
Initial WHI Report 2002
major finding
26% increase
in risk of breast cancer
My wife immediately asked me
Do I have a 26% chance of getting breast cancer since I
have taken hormones for more than 5 years? That is a
one in four chance. Is this really true?
My answer
No, the 26% increase represents only relative risk.
Her reply
What does that mean for me?
Important Issue
• We need to distinguish between:
– relative risk
– absolute risk
– excess risk
This is how I explain
this to my wife
One Million Women who marched in Washington
120,000 of these women or 12% will develop breast cancer in their lifetimes
This is absolute risk
12,000 or 1% will develop breast cancer in five years
Absolute risk
Lets consider just 1000 of these marchers
How many of these women will get
breast cancer within five years?
18 Women not receiving MHT will develop breast
cancer over a five year period
Absolute risk
26% increase
in relative risk in WHI
If these 1000 women take MHT for five years,
22 women will develop breast cancer
18 with breast cancer without MHT
22 with breast cancer with MHT
Excess risk 4
My Answer: Based on the WHI study, you will only
have a 4 in 1000 chance of getting a breast cancer
that you would not otherwise have gotten
if you take MHT for 5 years
WHI 10 years later
• Relative risk is only important when absolute risk
is high
• Example from common experience
Example of relative vs absolute risk
• If you take one plane flight your chances of crashing are one
in ten million (absolute risk)
• Your relative risk of crashing is increased by 500% if you take
five plane flights .
• Your excess risk by taking five flights rather than one is four
per ten million
• Bottom line: relative risk means little when absolute risk is low
• This is the reason to convert all WHI data to excess risk or
benefit
WHI 10 years later
• Need to consider all risk and benefit data
consistently
• The Endocrine Society has expressed all risks and
benefits as the number of women per 1000 using
MHT for 5 years who will experience event
What are the major excess risks
reported in the original WHI study?
WHI Estrogen plus Progestin MHT
# women/1,000/5 yrs
Excess Risks
10
8
6
4
2
0
E+P
WHI E+P
Average age 63
Benefits
Risks
What are the under-reported benefits?
Reduction in Mortality
# prevention/1,000/5 yrs
Under-reported Benefits (WHI)
30
25
20
15
10
5
0
E
E+P
Timing Hypothesis
Early vs. late treatment
Late
Early
5
5
4
4
3
3
2
2
1
1
0
0
1
1
2
2
3
3
4
5
E
E+P
4
5
E
E+P
Timing Hypothesis
Early vs. late treatment
Early
8
6
E
E+P
Late
8
6
4
4
2
2
0
0
2
2
4
4
6
6
8
8
E
E+P
VTE and Stroke
Similar relative increase in risk
but younger women experience
these problems less commonly
MHT 10 years after WHI
only used at start of menopause
Benefits
Risks
For Some in Menopause,
Hormones May Be Only Option
By TARA PARKER-POPE
New York Times
August 15, 2011
MHT 10 years after WHI
women with severe symptoms
Risks
Benefits
What to do about breast cancer risk?
Low risk of breast cancer
Benefit
High risk of breast cancer
Risk
Assess risk of breast cancer and only
treat those at low risk
• Low risk (i.e. 0.5% chance of breast cancer in 5
year) excess risk is 2.5/1000 per 5 years
• High risk (i.e. 4% chance of breast cancer in 5
years) excess risk 20/1000/5 years
Breast Cancer Risk Factors by Group
Estrogen Related Risk Factors
6
5
4
3
RR
2
1
0
Breast Cancer Risk Factors by Group
Estrogen Related Risk Factors
6
5
4
3
RR
2
1
0
Other Risk
Factors
Calculation of Breast Cancer Risk
• Gail Model
(http://www.cancer.gov/bcrisktoolmobile)
• Tyrer-Cuzick Model
(http://pulsescreening.co.uk/Corporate/Breast_can
cer_prediction_model-1.pdf)
For Some in Menopause,
Hormones May Be Only Option
By TARA PARKER-POPE
New York Times
August 15, 2011
WHI after 10 years
The Ultimate Goal is to provide the most benefit
to the patient while avoiding the most risks