Elsevier

The Lancet

Volume 362, Issue 9378, 12 July 2003, Pages 95-102
The Lancet

Articles
Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomized controlled trial

https://doi.org/10.1016/S0140-6736(03)13859-7Get rights and content

Summary

Background

As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an overtreatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radio-therapy and tamoxifen.

Methods

We used a 2×2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (i.e., in this case tamoxifen). Patients had complete surgical excision of the lesion con-firmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52·6 (range 2·4–118·3) months. Our primary endpoint was the incidence of ipsilateral invasive disease.

Findings

Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0·68 [0·49–0·96]; p=0·03). Radiotherapy reduced the incidence of ips-ilateral invasive disease (0·45 [0·24–0·85]; p=0·01) and ipsilateral ductal carcinoma in situ (0·36 [0·19–0·66]; p=0·0004), but there was no effect on the occurrence of contra-lateral disease. There was no evidence of interaction between radiotherapy and tamoxifen.

Interpretation

Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women.

Introduction

Before the National Health Service (NHS) breast screening programme was introduced in the UK in 1988, only a very small proportion of newly diagnosed breast cancers were ductal carcinoma in situ. However, the frequency of diagnosis of this type of disease was expected to increase as a result of the screening programme,1 and randomised trials were needed to define the best management of small impalpable screen-detected ductal carcinoma in-situ lesions. Before screening programmes, this form of breast cancer was often treated by mastectomy; although effective, this approach is probably an over-treatment for many lesions detected by screening. At that time, results of several randomised trials had shown that breast conservation for invasive cancer was a safe alternative to mastectomy,2, 3, 4, 5 but there was little evidence to recommend this treatment in women with ductal carcinoma in situ.

Since ipsilateral breast irradiation is useful in the management of invasive disease treated by complete local excision, we chose to assess this approach in the ductal carcinoma in situ trial. When our trial begain, two other trials of radiotherapy after breast-conserving surgery for women with ductal carcinoma in situ (NSABP B-17 and EORTC 10853) were recruiting patients, but results were not available.

We chose also to assess adjuvant tamoxifen in the study because of evidence that this treatment can reduce rates of ipsilateral and contralateral breast cancer in women who had breast-conserving surgery for invasive disease.6, 7 After our trial began, one other study (NSABP B-17 and EORTC 10853) were recruiting patients, but results were not available.

We chose also to assess adjuvant tamoxifen in the study because of evidence that this treatment can reduce rates of ipsilateral and contralateral breast cancer in women who had breast-conserving surgery for invasive disease.6, 7 After our trial began, one other study (NSABP B-24) started to investigate the role of tamoxifen in ductal carcinoma in situ after complete local incision and radiotherapy.8

In our 2·2 factorial trial, we aimed to compare the efficacy of complete local excision alone with excision followed by radiotherapy to the residual ipsilateral breast, or excision followed by tamoxifen for 5 years, or both, in reducing the incidence of subsequent ipsila-teral invasive breast carcinoma in patients with ductal carcinoma in situ.

Our second objective was to determine the incidence of subsequent ductal carcinoma in situ in the ipsilateral and contralateral breasts of patients treated by complete local excision alone with complete local excision followed by radiotherapy or tamoxifen.

Section snippets

Patients

We included patients who had unilateral or bilateral ductal carcinoma in situ detected in a breast screening programme, and who were deemed suitable for breast conservation. All UK centres in the national screening programme were invited to participate. The Australian- New Zealand Breast Cancer Trials Group (ANZBCTG) joined the trial in September, 1991. Patients with symptoms who had the ductal carcinoma in situ confirmed in the same way as in screening clinics were also eligible for inclusion.

Discussion

We report the first analysis of the 1694 eligible patients in the UK/ANZ Trial. Ipsilateral invasive disease was not reduced by tamoxifen. However, radiotherapy was associated with a reduced incidence of ipsilateral ductal carcinoma in situ, but there was no effect on contralateral incidence. 1030 patients were randomly allocated to the radiotherapy comparison, which is about the same number of patients investigated in each of the previously reported trials of radiation after breast conserving

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