Cancer Australia

Local excision alone without irradiation for ductal carcinoma in situ of the breast

July, 2010

Commentary by Winthrop Professor Christobel Saunders and Dr Mandy Taylor

The article

Hughes LL, Wang M, Page DL, et al. Local excision alone without irradiation for Ductal Carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009;27:5319-24

The reviewers

Winthrop Professor Christobel Saunders is Professor of Surgical Oncology at the School of Surgery, University of Western Australia. Dr Mandy Taylor is a Radiation Oncologist at Sir Charles Gairdner Hospital, Perth.

SUMMARY

Abbreviations

Contralateral Breast Event (CBE); Confidence Interval (CI); Ductal Carcinoma In Situ (DCIS); Disease-Free Survival (DFS); Ipsilateral Breast Event (IBE); Overall Survival (OS)

Study Design

This prospective single arm multi-institutional study investigates the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation. The study was conducted in North America and includes 565 cases of low/intermediate grade DCIS ≤ 2.5cm; and 105 high grade DCIS <1cm who had microscopic margin widths of 3 mm or wider and no residual calcifications on post-operative mammograms. Low/intermediate grade was defined by the presence of nuclear grade 1 or 2 with limited or no foci of necrosis. High grade was defined by the presence of nuclear grade 3 atypia and comedo-type necrosis that was zonal (ie present in contiguous ductal spaces). The median follow-up time was 6.3 years for all patients.

Findings

* to date no death has been due to breast cancer

Conclusion

The authors conclude that at 5 years after excision without irradiation, rigorously evaluated and selected patients with low/intermediate grade DCIS had acceptably low rates of IBE however patients with high grade DCIS had much higher rates. The authors suggest that for high grade DCIS, excision alone may be inadequate treatment.

COMMENTARY

What does this article add to existing clinical evidence in this area?

Radiotherapy for women with ‘low-intermediate risk’ DCIS after breast conserving surgery remains an area of clinical controversy. For example, in Western Australia we have two providers of radiotherapy services – and two different protocols for management of these patients.

DCIS has been placed high on the national agenda with the publication of the AIHW/NBOCC DCIS report¹ in March 2010. This reported that for women diagnosed with DCIS, the probability of developing a subsequent invasive breast cancer is 5% within 5 years and 11% within 10 years; this is four times as likely as the general Australian female population. For those aged under 40 at time of DCIS diagnosis, the probability of developing a subsequent invasive breast cancer is 8% within 5 years and 16% within 10 years; nearly 20 times as likely compared to other Australian women in this age group.

The reviewed article aims to evaluate the omission of radiotherapy in the treatment of selected patients with DCIS. It includes two cohorts of patients. Those with low-intermediate grade DCIS less than 2.5 cm, and those with less than 1cm of high grade DCIS, excised with clear (over 3mm) margins.

Accrual to the high-grade arm was slower than anticipated and could not be completed in a reasonable timeframe. Reasons for this are not clear and have not been addressed in the article. Despite being underpowered, the ipsilateral breast event (IBE) rate in the high-grade arm at 5 years was 15% and a third of these were invasive cancers. The authors considered this to be “unacceptably” high.

In the low-intermediate risk arm, the IBE rate at 5 years was 6% - which the authors suggested would be “acceptable” to many patients and physicians. However, with an increase in events (11% at 7 years) observed beyond 5 years, longer follow-up is needed. This may be particularly relevant for younger women because although only 20% of patients in the study were aged under 50 years, over 50% of subsequent breast events in the low-intermediate risk group were potentially life-threatening invasive cancers. How this translates into long term mortality is unknown.

How adequate was the methodology used in addressing the aim of this study?

This study is prospective, multi-institutional and, although not randomised, carefully conducted. Strengths of this study include rigorous, centralised pathology and imaging review and careful patient selection. The study is limited however by being a single-arm study of selected patients. In addition, only 5-year survival results are available, which are limited for a study of DCIS.

The investigators took the pragmatic decision to allow the use of tamoxifen after the 2000 publication of NSABP B-24. Nearly a third of the women joining after this time took the drug. Data from the National Breast Cancer Audit has indicated that tamoxifen is not routinely prescribed in Australia for DCIS management² which may potentially complicate the extrapolation of study results to local practice.

What are the implications of this study for clinical practice in Australia?

So how should we view this new data? While this is an interesting and potentially useful study which contributes to our knowledge about this heterogeneous disease, studies with more robust design and longer follow-up are needed to inform practice change. It provides some useful insights into the management of highly selected patients which may not be more generalisable; the majority of the patients in the study had lesions <1cm and margin width ≥5mm. Longer follow-up is required, in particular for the low-intermediate grade group. The recurrence rate in the low/intermediate risk group is said to be acceptable – we do not know if patients think this is the case but at least we now have a benchmark to inform them. A communication aid for clinicians to support discussions with women diagnosed with DCIS is available.^{3[^]}

Future RCTs as well as development of better biomarkers for recurrence and progression to invasion in DCIS will be vital to finally answer the questions on how best to manage DCIS and what effects our treatment have on long term survival. In the meantime, DCIS remains an enigmatic disease where our knowledge is just beginning to make inroads into better outcomes.

[^] The information contained in the communication aid pertaining to risk of ipsilateral breast events without radiotherapy was based on an earlier randomised trial with a 10 year follow-up.

References

1. Australian Institute of Health and Welfare & National Breast and Ovarian Cancer Centre 2010. Risk of invasive breast cancer in women diagnosed with ductal carcinoma in situ in Australia between 1995 and 2005. Cancer series no. 51. Cat. no. CAN 47. Canberra: AIHW.
2. Cuncins-Hearn A, Boult M, Babidge W et al. National Breast Cancer Audit: ductal carcinoma in situ management in Australia and New Zealand. ANZ Journal of Surgery. 77(1-2):64-8, 2007
3. National Breast and Ovarian Cancer Centre. Understanding ductal carcinoma in situ. National Breast and Ovarian Cancer Centre, Surry Hills, NSW, 2010.

Editor: Dr Anne Nelson, Evidence Review and Research Leader, National Breast and Ovarian Cancer Centre

Clinical Update – Breast Cancer Editorial Committee: Mr John Collins - Surgeon, Ms Jo Keyser - Specialist Breast Nurse, Dr Warwick Lee - Radiologist, A/Prof Liz Lobb – Senior Research Fellow, Dr Sue-Anne McLachlan - Medical Oncologist, Dr Sally Meade - Breast Surgeon, Dr Sue Pendlebury - Radiation Oncologist, A/Prof Martin Stockler - Medical Oncologist.

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