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.
- SourceAvailable from: Pascal Fenoglietto
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- "Therefore, BCS plus radiotherapy is an accepted strategy when mastectomy can be avoided, in view of the morbidity of radical surgery and the favorable prognosis of such patients. A number of randomized controlled trials of adjuvant radiotherapy have indeed demonstrated a reduced risk of both invasive and local recurrences, as well as a low risk of side effects  . A radiation boost to the tumor bed has been shown to significantly improve local control in patients with invasive breast cancer  . "
ABSTRACT: Ductal carcinoma in situ of the breast is associated with low mortality rates, but local relapse is a matter of concern in this disease. Risk factors for local relapse include young age, close or positive margins, and tumor necrosis. Whole breast irradiation following breast-conserving surgery for ductal carcinoma in situ significantly reduces the risk of local relapse as compared to breast-conserving surgery alone. Studies point to similar outcomes between breast-conserving surgery plus radiotherapy and mastectomy, in the absence of extensive disease. A complementary boost to the surgical bed improves outcomes for patients with invasive breast cancer. However, the effect of this strategy has never been prospectively reported for ductal carcinoma in situ. Two randomized controlled trials assessing this issue are ongoing. This paper represents an update on available literature about radiotherapy for DCIS with a special focus on the role of a radiotherapy boost to the tumor bed.04/2012; 2012:748196. DOI:10.1155/2012/748196
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ABSTRACT: Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial. Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870. Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial. This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision. Cancer Research UK and the Australian National Health and Medical Research Council.The Lancet Oncology 01/2011; 12(1):21-9. DOI:10.1016/S1470-2045(10)70266-7 · 24.73 Impact Factor
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ABSTRACT: The incidence of ductal carcinoma in situ (DCIS) of the breast has increased in recent decades, particularly, in counties offering mammography screening. The aims of the present study are to examine factors that may predict subsequent breast malignancy amongst patients with DCIS, and to compare the incidence of the subsequent malignancy and mortality with that of the general population. This population-based study includes all primary cases of pure DCIS diagnosed in Norway in the period 1993 to 2007 (N = 3167). The patients were followed to subsequent malignancy (DCIS or invasive cancer) or death. Risk estimates within 10 years of follow-up were calculated using Kaplan-Meier methods adjusting for competing risks, Cox regression models and Standard Incidence and Mortality Ratios. Patients with DCIS had a 11.2% risk of being diagnosed with a subsequent breast malignancy within 10 years (9.4% for invasive cancer), implying that they were five times as likely to be diagnosed with breast malignancy as the general female population in Norway. The risk was dependent on the treatment of the DCIS; patients treated with mastectomy and breast-conserving treatment had a 3.8 and 9.8% risk of ipsilateral invasive cancer within 10 years, respectively. Breast cancer mortality was 2.5% within 10 years of follow-up, a fourfold risk compared with the general population. Patients with DCIS have an increased risk of both subsequent breast malignancy and breast cancer death compared with women in the general population. Our results support previous knowledge of DCIS as a heterogeneous disease.Breast Cancer Research and Treatment 05/2011; 129(3):929-38. DOI:10.1007/s10549-011-1531-1 · 4.20 Impact Factor