Meta-analysis of trials of
radiotherapy in DCIS
Early Breast Cancer Trialists’
Collaborative Group (EBCTCG)
The world’s breast cancer trialists have
shared their data every 5 years
1985, 1990, 1995, 2000, 2005/6
Many MODERATE gains in long-term survival have
been identified
Together MODERATE gains from various treatment
improvements (and a moderate contribution from
breast screening) have almost halved UK/US
breast cancer mortality at ages 35-69
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EBCTCG 5th Cycle
EBCTCG 5th Cycle
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4
EBCTCG 5th Cycle
EBCTCG 5th Cycle
• Trials starting before 1 Jan 2000
• Events up to 30 Sept 2006
• Included trials of BCS±RT in DCIS for the
first time
– ie, trials of RT versus the same management
but without RT
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EBCTCG 5th Cycle
Randomized trials of BCS±RT in DCIS
Entry
Women
randomised
Median
followup
NSABP B-17
1985-90
818
EORTC 10853
1986-96
SweDCIS
UK/ANZ DCIS†
Study
Surgery*
Negative
margins
required
%
with
boost
16.5 y
WLE (37% ad)
Yes
9%
1010
10.4 y
WLE (20% ad)
Yes
5%
1987-99
1067
8.4 y
Sect res (17% ad)
No
2%
1990-98
1030
4.8 y
WLE (No ad)
Yes
NR‡
1999-06
636
N/A
WLE (No ad)
Yes
NR‡
Data available:
Data unavailable:§
RTOG 9804
* WLE: wide local excision; ad: axillary dissection; Sect res: sector resection
†
2x2 factorial design: ±RT±Tam
‡
Boost not recommended
§
Some patients still taking tamoxifen
Median follow-up for all trials with data available: 8.9 y
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EBCTCG 5th Cycle
Randomized trials of BCS±RT in DCIS
Eligibility of randomized patients for EBCTCG meta-analysis
Eligibility status
NSABP
B-17
EORTC
10853
Swedish
BCCG
UK/ANZ
Total
Eligible*
798
918
1,011
1,002
3,729
Ineligible†
20
92
56
28
196
Total
818
1,010
1,067
1,030
3,925
*Taking into account all information available to EBCTCG
†
Benign lesion only; microinvasion, invasion, Paget's disease, or other cancer
present at randomization; or other study-specific eligibility violation
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EBCTCG 5th Cycle
Randomized trials of BCS±RT in DCIS
Distribution of women by calendar year of randomisation
Calendar year
NSABP
B-17
EORTC
10853
Swedish
BCCG
UK/ANZ
Total
1985-89
71%
17%
6%
-
21%
1990-94
29%
60%
51%
46%
47%
1995-99
-
23%
43%
54%
32%
Total
100%
100%
100%
100%
100%
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EBCTCG 5th Cycle
Main outcome analysed:
• Ipsilateral breast recurrence
(either recurrence of CIS or occurrence of invasive cancer)
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
3729 women
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EBCTCG 5th Cycle
DCIS: BCS + RT vs.
BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Ratio of annual event rates by patient and
tumour characteristics
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DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Age at diagnosis
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Extent of breast-conserving surgery
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Use of tamoxifen (in both treatment arms)
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Method of DCIS detection
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Margin status
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Focality
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Histological grade
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Nuclear grade
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Comedonecrosis
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Architecture
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Clinical primary tumour size
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Pathological primary tumour size
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
among women with 1-20 mm tumours and negative margin status
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Ratio of annual event rates by age and histological grade
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DCIS: BCS + RT vs. BCS
Ips. BREAST RECURRENCE (CIS & Inv)
Ratio of annual event rates by age and comedonecrosis
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
3729 women
Contralateral breast events
Regional or distant events
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
3729 women
Any breast event *
*ie ipsilateral or contralateral DCIS, ipsilateral or contralateral invasive cancer,
regional or distant metastasis, or death certified as due to breast cancer 29
EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
3729 women
Mortality with a breast event
Mortality without a breast event
Mortality from all causes
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EBCTCG 5th Cycle
DCIS: BCS + RT vs. BCS
3729 women
Heart disease mortality
Non-breast primary cancer incidence
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EBCTCG 5th Cycle
EBCTCG analysis of radiotherapy in DCIS
Conclusions
• In these trials, radiotherapy halved the recurrence rate of
either DCIS or invasive cancer in the ipsilateral breast. After 5
years the absolute gain was about 10% (18% vs. 8%) and after
10 years it was about 15% (28% vs. 13%).
• The absolute gain in ‘low risk’ women was as large as in other
other women.
• The proportional reduction in the ipsilateral recurrence rate
was greater in women aged 50+ years than in younger
women.
• Radiotherapy had no significant effect on mortality from
breast cancer, at least to year 10.
• In these data, radiotherapy had no significant adverse effect
on cancers other than breast cancer, or on mortality from
non-breast cancer causes, including heart disease.
EBCTCG 5th Cycle
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