sabcs12 atlas pdf
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2012
S1-2. ATLAS 10 v 5 years of adjuvant tamoxifen
(TAM) in ER+ disease: Effects on outcome in the firstand in the second decade after diagnosis
Dr. Davies has no relevant financial relationshipsto disclose
Dr. Pan has no relevant financial relationships
to disclose Dr. Godwin has no relevant financial relationships
to disclose Dr. Gray has no relevant financial relationships
to disclose
Dr. Peto has no relevant financial relationshipsto disclose
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ATLAS - Adjuvant Tamoxifen: Longer Against Shorter
10 vs 5 years of adjuvant tamoxifen in ER+ disease:effects in the first & second decade after diagnosis
Presented on behalf of the
ATLAS collaborative group
All authors declare no relevant conflict of interest.
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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ER+ breast cancer: 15-year effects of adjuvant
tamoxifen on recurrence & breast cancer mortality
5 years of adjuvant tamoxifen vs none:
Previously published EBCTCG meta-analysis
10 years of adjuvant tamoxifen vs 5 years:ATLAS trial, LancetDecember 5, 2012*
* http://dx.doi.org/10.1016/S0140-6736(12)61963-1
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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Long-term effects of continuing adjuvant tamoxifen to 10 years vs
stopping at 5 years after diagnosis of oestrogen receptor-positive
breast cancer: ATLAS, a randomised trial
Christina Davies, Hongchao Pan, Jon Godwin, Richard Gray, Rodrigo Arriagada, Vinod Raina, Mirta Abraham, Victor Hugo Medeiros Alencar,Atef Badran, Xavier Bonfill, Joan Bradbury, Michael Clarke, Rory Collins, Susan R Davis, Antonella Delmestri, John F Forbes, Peiman Haddad,
Ming-Feng Hou, Moshe Inbar, Hussein Khaled, Joanna Kielanowska, Wing-Hong Kwan, Beela S Mathew, Bettina Mller, Antonio Nicolucci,
Octavio Peralta, Fany Pernas, Lubos Petruzelka, Tadeusz Pienkowski, Balakrishnan Rajan, Maryna T Rubach, Sera Tort, Gerard Urrtia,
Miriam Valentini, Yaochen Wang, Richard Peto, for the Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group*
SummaryBackground For women with oestrogen receptor (ER)-positive early breast cancer, treatment with
tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years
instead of stopping at 5 years.
Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than
stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10.
These results, taken together with results from previous trials of 5 years of tamoxifen treatment versusnone, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality
during the second decade after diagnosis.
Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU Biomed.
www.thelancet.comPublished online Dec 5, 2012 http://dx.doi.org/10.1016/S0140-6736(12)61963-1
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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ER+ early breast cancer: 15-year effects of
tamoxifen on recurrence & breast cancer mortality
5 years of adjuvant tamoxifen vs none:Previously published EBCTCG meta-analysis
10 years of adjuvant tamoxifen vs 5 years:ATLAS trial, LancetDecember 5, 2012*
* http://dx.doi.org/10.1016/S0140-6736(12)61963-1
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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*EBCTCG, Lancet2011; 378: 77184San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
5 years of tamoxifen versus no tamoxifen*
RECURRENCE BREAST CANCER MORTALITY
ER+ ER+
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ER+ disease, 5 yrs tamoxifen vs no tamoxifen
Breast cancer death rate ratio (RR), by period
5 yrs tam. vs 0:
meta-analysis
(n=10 645)
- years 0-4 0.71(0.62-0.80)
- years 5-9 0.66(0.58-0.75)
- years 10+ 0.73(0.62-0.86)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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10 years of tamoxifen vs 5: ATLAS(Adjuvant Tamoxifen - Longer Against Shorter)
6846 women with ER+ disease completed 5
years of tamoxifen, then were randomised to:
CONTINUE to year 10,or STOP at year 5.
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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10 years of tamoxifen vs 5
6846 women with ER+ disease completed 5
years of tamoxifen, then were randomised:
CONTINUE to year 10,or STOP at year 5.
25% Asia/mid-East, 28% Latin America,
47% Europe/US/ANZ/South Africa
54% node-negative
8 yrs follow-up: compliance, recurrence, deathSan Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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10 years of tamoxifen vs 5
6846 women with ER+ disease completed 5
years of tamoxifen, then were randomised:
CONTINUE to year 10,or STOP at year 5.
Recurrence: 617 vs 711 women (2p=0.002)
Breast cancer mortality: 331 vs 397 (2p=0.01)
Overall mortality: 639 vs 722 (2p=0.01)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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10 years of tamoxifen vs 5
6846 women with ER+ disease completed 5
years of tamoxifen, then were randomised:
CONTINUE to year 10,or STOP at year 5.
Recurrence and breast cancer mortality:
Little effect during years 5-9;
benefit mainly after year 10
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
ATLAS: 6846 women, ER+, 10 vs 5 years tamoxifen
RECURRENCE BREAST CANCER MORTALITY
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ER+ disease, 5 yrs tam. vs 0, and 10 yrs vs 5 yrs.
Breast cancer death rate ratio (RR), by period
5 yrs tam. vs 0:
meta-analysis
(n=10 645)
10 yrs tam. vs 5:
ATLAS trial
(n=6846)
- years 0-4 0.71(0.62-0.80) (1.0)
- years 5-9 0.66(0.58-0.75) 0.97 (0.79-1.18)
- years 10+ 0.73(0.62-0.86) 0.71 (0.58-0.88)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
p=0.0016
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ER+ disease, 5 yrs tam. vs 0, and 10 yrs vs 5 yrs.
Breast cancer death rate ratio (RR), by period
5 yrs tam. vs 0:meta-analysis
(n=10 645)
10 yrs tam. vs 5:ATLAS trial
(n=6846)
10 yrs tam. vs 0(estimated as
product of RRs)
- years 0-4 0.71(0.62-0.80) (1.0) 0.71 (0.62-0.81)
- years 5-9 0.66(0.58-0.75) 0.97 (0.79-1.18) 0.64 (0.50-0.82)
- years 10+ 0.73(0.62-0.86) 0.71 (0.58-0.88) 0.52 (0.40-0.68)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
10 yrs tam. reduces breast cancer mortality by
a third in first decade & half in second decade
p=0.0016
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San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
Trials under-estimate real benefits
Analyses by allocated treatment suggest that
10 yrs tam. reduces breast cancer mortality by
a third in first decade & half in second decade,
so actual use of 10 yrs tam. has a greater effect.
5 yrs tam vs 0: compliance after 2 years ~80%
10 yrs tam vs 5 (ATLAS): at 2 yrs, 84% vs 4% use(difference in proportions using tam. ~80%)
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Compliance: 2 years after ATLAS randomisation,
84% of CONTINUE versus 4% of STOP were taking
tamoxifen (80% difference between proportions)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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Side effects and main effects of 10 yrs tam. on
15-yr mortality in meta-analysis & ATLAS trial
5 yrs tam. vs 0:
meta-analysis
10 yrs tam. vs 5:
ATLAS trial
10 yrs tam. vs 0
(by addition)
Endometrial
cancer & PEmortality
0.2% loss 0.2% loss 0.4% loss
Breast
cancer
mortality
9% gain 3% gain 12% gain
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
Estimated effects of 10 yrs tam. vs 0 on 15-yr
mortality: absolute gain ~30x absolute loss
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San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
Further research
- 2013: aTTom (UK counterpart of ATLAS)- 2013: EBCTCG meta-analysis of 10 vs 5 yr
- 2017: 5 more years of ATLAS follow-up
Generalizability to other endocrine drugs of
later benefit from 10 vs 5 years treatment?
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San Antonio Breast Cancer Symposium
Cancer Therapy and Research Center at UT
Health Science Center December 4-8, 2012
This presentation is the intellectual property
of ATLAS. Contact [email protected] for
permission to reproduce or distribute.
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ER+ disease: effects of adjuvant tamoxifen duration on breast cancer mortality
Left: 5 years tam. vs none (EBCTCG meta-analysis), Right: 10 vs 5 years (ATLAS)
Group allocated ~5y tamoxifen:
15.0% die between years 5-15
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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ER+ disease: Effects of tamoxifen duration on
event rate ratio (RR), by time since diagnosis
5 years tam. vs none:EBCTCG meta-analysis
(n=10 645)
Recurrence in:
- years 0-4 RR=0.53 (0.48-0.57)
- years 5-9 0.68 (0.60-0.78)
- years 10+ 0.94 (0.79-1.12)
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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ER+ disease: Effects of tamoxifen duration on
event rate ratio (RR), by time since diagnosis
5 years tam. vs none:EBCTCG meta-analysis
(n=10 645)
Recurrence in:
- years 0-4 RR=0.53 (0.48-0.57)
- years 5-9 0.68 (0.60-0.78)
- years 10+ 0.94 (0.79-1.12)
Breast cancer
mortality in:
- years 0-4 0.71 (0.62-0.80)
- years 5-9 0.66 (0.58-0.75)
- years 10+
0.73 (0.62-0.86)
2p=0.0001
San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 4-8, 2012
This presentation is the intellectual property of ATLAS. Contact [email protected] for permission to reproduce or distribute.
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ER+ disease: Effects of tamoxifen duration on
event rate ratio (RR), by time since diagnosis
5 years tam. vs none:EBCTCG meta-analysis
(n=10 645)
10 years tam. vs 5:ATLAS trial
(n=6846)
Recurrence in:
- years 0-4 RR=0.53 (0.48-0.57) (1.0)
- years 5-9 0.68 (0.60-0.78) 0.90 (0.79-1.02)
- years 10+ 0.94 (0.79-1.12) 0.75* (0.62-0.90)
Breast cancer
mortality in:
- years 0-4 0.71 (0.62-0.80) (1.0)
- years 5-9 0.66 (0.58-0.75) 0.97 (0.79-1.18)
- years 10+
0.73 (0.62-0.86)
2p=0.0001
0.71 (0.58-0.88)
2p=0.0016 * 2p
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ER+ disease: Effects of tamoxifen duration on
event rate ratio (RR), by time since diagnosis
5 years tam. vs none:EBCTCG meta-analysis
(n=10 645)
10 years tam. vs 5:ATLAS trial
(n=6846)
10 years tam. vs none:estimated effects
(product of two RRs)
Recurrence in:
- years 0-4 RR=0.53 (0.48-0.57) (1.0) RR=0.53 (0.48-0.57)
- years 5-9 0.68 (0.60-0.78) 0.90 (0.79-1.02) 0.61 (0.51-0.73)
- years 10+ 0.94 (0.79-1.12) 0.75* (0.62-0.90) 0.70* (0.54-0.91)
Breast cancer
mortality in:
- years 0-4 0.71 (0.62-0.80) (1.0) 0.71 (0.62-0.81)
- years 5-9 0.66 (0.58-0.75) 0.97 (0.79-1.18) 0.64 (0.50-0.82)
- years 10+
0.73 (0.62-0.86)
2p=0.0001
0.71 (0.58-0.88)
2p=0.0016
0.52 (0.40-0.68)
* 2p