Jack Cuzick, Ph.D. Wolfson Institute of Preventive Medicine St Bartholomew’s Medical School...
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![Page 1: Jack Cuzick, Ph.D. Wolfson Institute of Preventive Medicine St Bartholomew’s Medical School London, United Kingdom Implementation Issues for Chemoprevention.](https://reader036.fdocuments.us/reader036/viewer/2022070323/56649d9d5503460f94a86a0c/html5/thumbnails/1.jpg)
Jack Cuzick, Ph.D.Wolfson Institute of Preventive Medicine
St Bartholomew’s Medical School London, United Kingdom
Implementation Issues
for Chemoprevention
of Breast Cancer
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thousandsthousands
World-wide Burden of Cancer in Women
GLOBOCAN 2002GLOBOCAN 2002
Incidence
Mortality
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Breast Cancer Prevention Trials using Tamoxifen
Trial (Entry Dates)
Population Number Randomised
Agents (vs Placebo)
and daily dose
Intended Duration of Treatment
Royal Marsden (1986-1996)
High Risk Family History
2471 Tamoxifen 20mg 5-8y
NSABP-P1 (1992-1997)
High risk women >1.6% 5y risk
13 388 Tamoxifen 20mg 5y
Italian (1992-1997)
Normal Risk Hysterectomy
5408 Tamoxifen 20mg 5y
IBIS-I (1992-2001)
>2-fold relative risk 7139 Tamoxifen 20mg 5y
Adjuvant Overview (1976-1995)
Women with ER+ operable breast
cancer in 11 trials
~15000 Tamoxifen 20-40mg with or without
chemotherapy in both arms.
3 years or more
(average ~5 yrs)
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Tamoxifen Overview : ER Positive Invasive Breast Cancer
All Tam Prev
IBIS
Italian
P1
Marsden
.1 .3 .52 1 1.5 Odds Ratio
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Outcome in 1000 women at high risk of breast cancer followed for 5 years
No TreatmentTamoxifen for 5 years
Breast Cancer
VTE
Endometrial Cancer
30 19
6 12
2 5
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Prevention Trials using Raloxifene
Trial (Entry Dates)
Population Number Randomised
Agents (vs Placebo)
and daily dose
Intended Duration of Treatment
MORE
(1994-1999)
Normal Risk
Post-menopausal women with
osteoporosis
7705
Raloxifene 60 or
120mg (3 arm)
4y
CORE
(2000-2004)
Normal Risk
Post-menopausal women with
osteoporosis
4011
Raloxifene 60mg
Additional 4y
RUTH
(1998-2000)
STAR (2001 -2005)
Post menopausal women ? 55y with CHD or risk factor
High risk post-menopausal women
>1.6% 5y risk
10101
19 747
Raloxifene 60mg
Raloxifene 60mg vs Tamoxifen
(20mg)
5y
5y
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ALL INVASIVE BREAST CANCERS, 0-10ySERM vs. placebo
Fixed-effect model: -38.3% [-44.2%;-29.6%], p<0.001Fixed-effect model: -38.3% [-44.2%;-29.6%], p<0.001Random-effect model: -39.3% [-51.1%;-24.7%], p<0.001Random-effect model: -39.3% [-51.1%;-24.7%], p<0.001
Test for heterogeneity: Q(8df) = 23.79, p=0.002Test for heterogeneity: Q(8df) = 23.79, p=0.002
Hazard ratio.1 .2 .5 1 2 5 10
Combined
PEARL 50 mg
PEARL 25 mg
STAR
RUTH
MORE/CORE
Marsden
IBIS1
NSABP P1
Italian
Tamoxifen vs. placebo
Raloxifene vs. placebo
Lasofoxifene vs. placebo
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Contralateral Tumours in Aromatase Inhibitor Trials
Odds Ratio (log scale)
.3 .5 1 1.5 Combined
B-33
MA-17
IES
ITA/ARNO/ABCSG
BIG 1-98
ATAC
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New (Contralateral) Breast Primaries - AI adjuvant trials
47%
50%
ATAC
EBCTCG
? 75%
0
10
20
30
40
50
60
70
80
90
100
Anastrozole Tamoxifen Placebo
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MAP3 - Cumulative Incidence of Invasive Breast
Cancer
Goss et al NEJM, 2011
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IBIS II- PREVENTION STRATUM
n = 4,000 High Risk
• High Risk Post-menopausal women, aged 40-70.• Placebo controlled 2-arm trial for high risk• 5 Year Treatment
RANDOMISATION
PLACEBOANASTROZOLE
1mg
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Implementation Issues
• No agents licensed for prevention in Europe
• Tamoxifen and Raloxifene approved in the US
• Only manufacturer can apply for license
• All drugs off patent protection