Adjuvant radiotherapy for DCIS
Authors: JP Julien, N Bijker, IS Fentiman, JL Peterse
Journal: The Lancet (2000)

Authors' replySir—Although some have described the benefits of breast irradiation for DCIS as a Pyrrhic victory, the results of the EORTC 10853 trial do, nevertheless, contribute to an advance in evidencebased medicine. For some time the only published randomised trial for DCIS was the B-17 study,1Fisher B Costantino J Redmond C et al.Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer.N Engl J Med. 1993; 328: 1581-1586Crossref PubMed Scopus (622) Google Scholar done by the NSABP, the results of which have not been universally reproducible. EORTC 10853 and NSABP B-17 had similar designs and showed that radiotherapy could reduce the risk of recurrence. However, the 3·5-fold reduction in invasive progression found in NSABP B-17 was not quantitatively confirmed. The increased incidence of contralateral cancers in the irradiated group, although probably a chance finding, does remain a concern. Since the carcinogenic effect of irradiation would be expected to occur many years after the event, we will closely monitor the participants to assess this phenomenon after longer follow-up. However, we agree with David Brenner and colleagues that the available evidence on radio-induced breast cancer makes a causal relation between irradiation and contralateral breast cancer unlikely. The use of tamoxifen was not recommended in the protocol. We requested information about any anticancer drugs given, and only incidentally the use of tamoxifen was mentioned. Tamoxifen use was balanced over the two treatment arms.Kefah Mokbel and colleagues point out that other factors, such as the extent of local surgery and hence the width of DCIS-free margin, might play an important part in risk of local recurrence. We agree that there is a need for subgroups, which have a very low risk of recurrence and progression and so might be treated safely without irradiation, to be defined. Even more importantly, we feel that those patients with an unacceptably high risk of invasive progression after breastconserving treatment for DCIS should be identified so that they can be offered mastectomy with immediate reconstruction to minimise their risk of subsequent metastatic disease. Many studies have attempted to identify risk factors for relapse but most are not randomised and suffer selection bias. The minimum free margin of 10 mm or more recommended by Silverstein and colleagues2Silverstein MJ Lagios MD Groshen S et al.The influence of margin width on local control of ductal carcinoma in situ of the breast.N Engl J Med. 1999; 340: 455-461Crossref PubMed Scopus (635) Google Scholar has not been confirmed by any other study. Silverstein and colleagues have acknowledged that they have not proved their hypothesis that radiotherapy is of no benefit in patients with a margin width of 10 mm or more.3Silverstein MJ Groshen S Waisman JR Treatment of ductal carcinoma in situ.N Engl J Med. 1999; 341: 998-1000Crossref Scopus (2) Google ScholarThe EORTC trial was designed to investigate the role of radiotherapy in breast-conserving treatment for DCIS. Because of the large scale of the trial, with 42 centres participating, it was not possible to assess margin status in all patients, despite an attempt to standardise pathological handling of specimens. Accurate measurement of margin width requires uniform work-up of the resected specimen including inking of margins, sectioning, and radiography of the lamellated specimen, and representative sampling of suspect areas and margins. The results of a central pathology review, including both clinical and pathological risk-factor analysis will soon be available.Achieving complete local excision of a non-palpable DCIS is a technically difficult procedure and local recurrence often reflects failed complete excision. Radiotherapy has been proved to reduce risk of relapse and progression by one third in two randomised trials. Until randomised studies have confirmed that there are subgroups of patients who can be safely treated by local excision alone, the available evidence indicates that breast conservation for patients with DCIS should include complete local excision and breast irradiation. Authors' reply Sir—Although some have described the benefits of breast irradiation for DCIS as a Pyrrhic victory, the results of the EORTC 10853 trial do, nevertheless, contribute to an advance in evidencebased medicine. For some time the only published randomised trial for DCIS was the B-17 study,1Fisher B Costantino J Redmond C et al.Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer.N Engl J Med. 1993; 328: 1581-1586Crossref PubMed Scopus (622) Google Scholar done by the NSABP, the results of which have not been universally reproducible. EORTC 10853 and NSABP B-17 had similar designs and showed that radiotherapy could reduce the risk of recurrence. However, the 3·5-fold reduction in invasive progression found in NSABP B-17 was not quantitatively confirmed. The increased incidence of contralateral cancers in the irradiated group, although probably a chance finding, does remain a concern. Since the carcinogenic effect of irradiation would be expected to occur many years after the event, we will closely monitor the participants to assess this phenomenon after longer follow-up. However, we agree with David Brenner and colleagues that the available evidence on radio-induced breast cancer makes a causal relation between irradiation and contralateral breast cancer unlikely. The use of tamoxifen was not recommended in the protocol. We requested information about any anticancer drugs given, and only incidentally the use of tamoxifen was mentioned. Tamoxifen use was balanced over the two treatment arms. Kefah Mokbel and colleagues point out that other factors, such as the extent of local surgery and hence the width of DCIS-free margin, might play an important part in risk of local recurrence. We agree that there is a need for subgroups, which have a very low risk of recurrence and progression and so might be treated safely without irradiation, to be defined. Even more importantly, we feel that those patients with an unacceptably high risk of invasive progression after breastconserving treatment for DCIS should be identified so that they can be offered mastectomy with immediate reconstruction to minimise their risk of subsequent metastatic disease. Many studies have attempted to identify risk factors for relapse but most are not randomised and suffer selection bias. The minimum free margin of 10 mm or more recommended by Silverstein and colleagues2Silverstein MJ Lagios MD Groshen S et al.The influence of margin width on local control of ductal carcinoma in situ of the breast.N Engl J Med. 1999; 340: 455-461Crossref PubMed Scopus (635) Google Scholar has not been confirmed by any other study. Silverstein and colleagues have acknowledged that they have not proved their hypothesis that radiotherapy is of no benefit in patients with a margin width of 10 mm or more.3Silverstein MJ Groshen S Waisman JR Treatment of ductal carcinoma in situ.N Engl J Med. 1999; 341: 998-1000Crossref Scopus (2) Google Scholar The EORTC trial was designed to investigate the role of radiotherapy in breast-conserving treatment for DCIS. Because of the large scale of the trial, with 42 centres participating, it was not possible to assess margin status in all patients, despite an attempt to standardise pathological handling of specimens. Accurate measurement of margin width requires uniform work-up of the resected specimen including inking of margins, sectioning, and radiography of the lamellated specimen, and representative sampling of suspect areas and margins. The results of a central pathology review, including both clinical and pathological risk-factor analysis will soon be available. Achieving complete local excision of a non-palpable DCIS is a technically difficult procedure and local recurrence often reflects failed complete excision. Radiotherapy has been proved to reduce risk of relapse and progression by one third in two randomised trials. Until randomised studies have confirmed that there are subgroups of patients who can be safely treated by local excision alone, the available evidence indicates that breast conservation for patients with DCIS should include complete local excision and breast irradiation. Adjuvant radiotherapy for DCISThe investigators of the European Organization for Research and Treatment of Cancer (EORTC) (Feb 12, p 528)1 on breast-conserving surgery with or without radiation for treatment of ductal carcinoma in situ (DCIS) point out that if their finding that there is an increased rate of cancers in the contralateral breast in the surgery plus radiation group was truly radiation induced, it might well cancel out (and more) the clinical gains afforded by adjuvant radiotherapy. Full-Text PDF Adjuvant radiotherapy for DCISJean-Pierre Julien and colleagues1 observed that adjuvant radiotherapy after breast-conserving surgery for DCIS significantly reduced the incidence of local recurrence. Their results are comparable to those of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 study. Furthermore, their definition of complete excision and clear margins (absence of malignant cells at the inked margins) was comparable to that of the NSABP B-17 trial. It is very likely that the benefits of radiotherapy in both studies reflect the effects of radiotherapy on residual disease. Full-Text PDF Adjuvant radiotherapy for DCISThe early results of the EORTC trial1 confirmed the results of the similar NSABP B-17 trial.2 Radiotherapy in this situation reduced significantly the risk of subsequent occurrences (invasive or non-invasive) in the irradiated breast. This is somewhat grudgingly conceded by Melvin Silverstein and Michael Lagios in their commentary.3 We would, however, take issue with two points they raise. Full-Text PDF Adjuvant radiotherapy for DCISThe EORTC 10853 study1 shows, like the NSABP B-17 study,2 that postoperative radiotherapy for DCIS reduces both invasive and non-invasive recurrences in the ipsilateral breast. However unlike B-17, the EORTC study showed an increased number of contralateral breast events in the patients randomly allocated adjuvant radiation (8 vs 21; p=0·01). The investigators suggest that the increase might be a consequence of the radiation. We feel this is highly improbable given the short latency time, the low doses scattered to the contralateral breast, and the lack of such an effect in numerous studies where radiation has been used to treat invasive disease. Full-Text PDF