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 2002major finding

26% increasein risk of breast cancer

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 wife immediately asked me

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 MHT22 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

Excess Risks

# w

omen

/1,0

00/5

yrs

0

2

4

6

8

10 E+P

Risks

Benefits

WHI E+P

Average age 63

What are the under-reported benefits?

Reduction in Mortality

Under-reported Benefits (WHI)#

pre

vent

ion

/1,0

00

/5 y

rs

0

5

10

15

20

25

30EE+P

Timing HypothesisEarly vs. late treatment

Early Late5

4

3

2

1

0

5

4

3

2

1

EE+P

EE+P

5

4

3

2

1

0

5

4

3

2

1

Timing HypothesisEarly vs. late treatment

Early Late

4

2

0

6

4

2

8

6

8

EE+P

4

2

0

6

4

2

8

6

8EE+P

VTE and Stroke

Similar relative increase in risk but younger women experience these problems less commonly

MHT 10 years after WHIonly used at start of menopause

RisksBenefits

For Some in Menopause, Hormones May Be Only Option

By TARA PARKER-POPE

New York TimesAugust 15, 2011

MHT 10 years after WHIwomen with severe symptoms

Risks

Benefits

What to do about breast cancer risk?

Benefit

Low risk of breast cancer

Risk

High risk of breast cancer

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

RR

Estrogen Related Risk Factors

0

1

2

3

4

5

6Bre

ast

Den

sity

Breast Cancer Risk Factors by Group

Plas

ma

E2Age

at

Men

opau

seAge

at

1st L

ive

birt

h

BM

IAge

at

Men

arch

e

MH

T

RR

Estrogen Related Risk Factors

0

1

2

3

4

5

6Other Risk

FactorsBre

ast

Den

sity

Plas

ma

E2Age

at

Men

opau

seAge

at

1st L

ive

birt

h

BM

IAge

at

Men

arch

e

MH

T1

o Rel

ativ

e2

o Rel

ativ

e

Alc

ohol

Breast Cancer Risk Factors by Group

Calculation of Breast Cancer Risk

• Gail Model (http://www.cancer.gov/bcrisktoolmobile)

• Tyrer-Cuzick Model (http://pulsescreening.co.uk/Corporate/Breast_cancer_prediction_model-1.pdf)

For Some in Menopause, Hormones May Be Only Option

By TARA PARKER-POPE

New York TimesAugust 15, 2011

WHI after 10 years

The Ultimate Goal is to provide the most benefit

to the patient while avoiding the most risks