Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast

Abstract

Individual patient data were available for all four of the randomized trials that began before 1995, and that compared adjuvant radiotherapy vs no radiotherapy following breast-conserving surgery for ductal carcinoma in situ (DCIS). A total of 3729 women were eligible for analysis. Radiotherapy reduced the absolute 10-year risk of any ipsilateral breast event (ie, either recurrent DCIS or invasive cancer) by 15.2% (SE 1.6%, 12.9% vs 28.1% 2 P <.00001), and it was effective regardless of the age at diagnosis, extent of breast-conserving surgery, use of tamoxifen, method of DCIS detection, margin status, focality, grade, comedonecrosis, architecture, or tumor size. The proportional reduction in ipsilateral breast events was greater in older than in younger women (2P < .0004 for difference between proportional reductions; 10-year absolute risks: 18.5% vs 29.1% at ages <50 years, 10.8% vs 27.8% at ages ≥ 50 years) but did not differ significantly according to any other available factor. Even for women with negative margins and small low-grade tumors, the absolute reduction in the 10-year risk of ipsilateral breast events was 18.0% (SE 5.5, 12.1% vs 30.1%, 2P = .002). After 10 years of follow-up, there was, however, no significant effect on breast cancer mortality, mortality from causes other than breast cancer, or all-cause mortality.

Figure 1

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) (four trials, start dates 1985–1990, 3729 women): 10-year cumulative risks of any ipsilateral breast event (ie recurrent DCIS or invasive cancer). Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 2

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): ratio of annual event rates of any ipsilateral breast event by trial. SE = standard error; CI = confidence interval.

Figure 3

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): 10-year cumulative risks of any ipsilateral breast event by age at diagnosis, extent of surgery, and use of tamoxifen (3729 women). Women given sector resection were from either the SweDCIS trial (1011 women) or the EORTC 10853 trial (135 women), and women using tamoxifen were all in the UK/ANZ DCIS trial. Information was not available on estrogen or progesterone receptor status. Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 4

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): 10-year cumulative risks of any ipsilateral breast event by detection method (2619 women), margin status (3355 women) and focality (1526 women). Women for whom the surgical margins were close (<2 mm) were classified as having negative surgical margins. Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 5

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): 10-year cumulative risks of any ipsilateral breast event by histological grade (1794 women) and nuclear grade (1617 women). Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 6

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): 10-year cumulative risks of any ipsilateral breast event by comedonecrosis (1332 women) and architecture (1388 women). Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 7

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): 10-year cumulative risks of any ipsilateral breast event by clinical tumor size (1192 women) and pathological tumor size (1631 women). Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 8

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): Ratio of annual event rates of any ipsilateral breast event by various patient and tumor characteristics. SE = standard error; CI = confidence interval.

Figure 9

Effect of radiotherapy (RT) after breast-conserving surgery (BCS): ratio of annual event rates of any ipsilateral breast event by age and histological grade and age and comedonecrosis. SE = standard error; CI = confidence interval.

Figure 10

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 724 women with negative margin status and pathological tumor size 1–20 mm according to nuclear grade: 10-year cumulative risks of any ipsilateral breast event. Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 11

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 3729 women: 10-year cumulative risks of any breast event, any contralateral breast event and any regional or distant event. NS = not statistically significant. Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.

Figure 12

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 3729 women: 10-year cumulative risks of breast cancer mortality, mortality without a breast event (ie, mortality from causes other than breast cancer in the period before a breast event), and any death. (Analysis based on first events only.) NS = not statistically significant. Vertical lines indicate 1 SE above or below the 5 and 10 year percentages.