Meta-analysis of trials of radiotherapy in DCIS

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG)

EBCTCG 5th Cycle 2

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

3EBCTCG 5th Cycle

#

EBCTCG 5th Cycle 4

EBCTCG 5th Cycle 5

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

EBCTCG 5th Cycle 6

Randomized trials of BCS±RT in DCIS

Study Entry Women random-

ised

Median follow-

up Surgery*

Negative margins required

%

with boost

Data available:

NSABP B-17 1985-90 818 16.5 y WLE (37% ad) Yes

9%

EORTC 10853 1986-96 1010 10.4 y WLE (20% ad) Yes

5%

SweDCIS 1987-99 1067 8.4 y Sect res (17% ad) No

2%

UK/ANZ DCIS† 1990-98 1030 4.8 y WLE (No ad) Yes NR‡

Data unavailable:§

RTOG 9804 1999-06 636 N/A WLE (No ad) Yes NR‡

* 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

EBCTCG 5th Cycle 7

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

EBCTCG 5th Cycle 8

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%

EBCTCG 5th Cycle 9

Main outcome analysed:

• Ipsilateral breast recurrence

(either recurrence of CIS or occurrence of invasive cancer)

EBCTCG 5th Cycle 10

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

EBCTCG 5th Cycle 11

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

3729 women

12

DCIS: BCS + RT vs. BCS

Ips. BREAST RECURRENCE (CIS & Inv)

Ratio of annual event rates by patient and tumour characteristics

EBCTCG 5th Cycle 13

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Age at diagnosis

EBCTCG 5th Cycle 14

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Extent of breast-conserving surgery

EBCTCG 5th Cycle 15

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Use of tamoxifen (in both treatment arms)

EBCTCG 5th Cycle 16

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Method of DCIS detection

EBCTCG 5th Cycle 17

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Margin status

EBCTCG 5th Cycle 18

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Focality

EBCTCG 5th Cycle 19

DCIS: BCS + RT vs. BCS Ips. BREAST RECURRENCE (CIS & Inv)

Histological grade

EBCTCG 5th Cycle 20

DCIS: BCS + RT vs. BCS Ips. BREAST RECURRENCE (CIS & Inv)

Nuclear grade

EBCTCG 5th Cycle 21

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Comedonecrosis

EBCTCG 5th Cycle 22

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Architecture

EBCTCG 5th Cycle 23

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Clinical primary tumour size

EBCTCG 5th Cycle 24

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Pathological primary tumour size

EBCTCG 5th Cycle 25

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

among women with 1-20 mm tumours and negative margin status

26

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Ratio of annual event rates by age and histological grade

EBCTCG 5th Cycle 27

DCIS: BCS + RT vs. BCSIps. BREAST RECURRENCE (CIS & Inv)

Ratio of annual event rates by age and comedonecrosis

EBCTCG 5th Cycle 28

DCIS: BCS + RT vs. BCS3729 women

Contralateral breast events Regional or distant events

EBCTCG 5th Cycle 29

DCIS: BCS + RT vs. BCS3729 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

EBCTCG 5th Cycle 30

DCIS: BCS + RT vs. BCS3729 women

Mortality with a breast event Mortality without a breast event Mortality from all causes

EBCTCG 5th Cycle 31

DCIS: BCS + RT vs. BCS3729 women

Heart disease mortality Non-breast primary cancer incidence

32

EBCTCG analysis of radiotherapy in DCISConclusions

• 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