Practice Uncertainties

Should patients with ductal carcinoma in situ be treated with adjuvant whole breast radiotherapy after breast conservation surgery?

BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1410 (Published 17 May 2018) Cite this as: BMJ 2018;361:k1410
  1. Jessamy Bagenal, senior medical editor, The Lancet1,
  2. Nicola Roche, consultant breast surgeon1,
  3. Gill Ross, consultant clinical oncologist1,
  4. Anna Kirby, consultant clinical oncologist1,
  5. David Dodwell, consultant clinical oncologist2
  1. 1The Royal Marsden Hospital, London, UK
  2. 2Nuffield Department of Population Health, University of Oxford, Oxford, UK
  1. Correspondence to J Bagenal jessamy.bagenal{at}googlemail.com

What you need to know

  • Women with ductal carcinoma in situ are usually offered breast conserving surgery (BCS), often followed by whole breast radiotherapy (WBRT).

  • WBRT reduces ipsilateral breast events but there is insufficient evidence that it improves breast cancer specific or overall mortality.

  • Patients will have different perceptions of the risks and benefits of WBRT and should be assisted in their decision making by clear presentation of the information.

Ductal carcinoma in situ (DCIS) affects around 8000 women a year in the UK.1 Since the introduction of mammographic screening, the incidence of DCIS has increased and it now represents around 20% of all new screen detected breast cancers.2

DCIS is categorised into low, intermediate, and high grade based on histological features. Most cases of DCIS are treated with breast conserving surgery (BCS), often followed by whole breast radiotherapy (WBRT). An individual patient level meta-analysis (four randomised controlled trials, 3729 women) found that WBRT approximately halved the rate of ipsilateral DCIS or invasive recurrence at 10 years compared with no radiotherapy following BCS.3 However, WBRT can cause side effects such as impaired cosmesis, skin changes, and late cardiac toxicity4 Patients might also find WBRT inconvenient and expensive.

National Institute of Health and Care Excellence (NICE) guidelines recommend offering WBRT to all patients with DCIS treated by BCS.5 The European Society of Medical Oncology guidelines suggest that WBRT might be omitted in some low risk patients.6

However, observational studies done in the UK, US, and Europe note wide variations in the use of adjuvant radiotherapy in these patients.7 This variation possibly reflects uncertainty as to whether the benefits of WBRT are large enough to warrant the blanket use of adjuvant WBRT or whether WBRT can be safely omitted in a subset of lower risk patients.

In this article we discuss the evidence surrounding radiotherapy use in DCIS.

What is the evidence of uncertainty?

Search strategy

We searched the Cochrane Library (including the Cochrane Central Database of Controlled Trials), Ovid Medline, and clinical trial registers (clinicaltrials.gov, controlled-trials.com, who.int/trialsearch), PROSPERO, National Cancer Research Institute portfolio, Cancer Research UK, and Macmillan websites from 1990 until May 2017. We also cross referenced bibliographies. We ran multiple searches using the terms:

“Ductal carcincoma,” “DCIS” AND “RADIOTHERAPY,” “DCIS” AND “Treatment” in combination and alone. We selected manuscripts and trials that were most relevant to the article through discussion between the authors.

What is the risk of an ipsilateral breast event in a DCIS patient?

Evidence from three prospective studies in patients with DCIS who have undergone BCS suggests that the risk of an ipsilateral breast event continues to rise with time. 8-11These studies failed to identify a sufficiently low risk group of patients that gain no appreciable benefit in terms of a reduced risk of recurrence from WBRT. In a trial with 636 women with low or intermediate grade DCIS, at a median follow-up of seven years, the ipsilateral event rate was 0.9% in the WBRT arm versus 6.7% in the observation arm (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.47; P<.001).9 A single-arm trial in 158 women with low and intermediate grade DCIS closed early as the ipsilateral breast event rate of 2.4% per patient-year met the predetermined stopping rules.10 In another prospective non-randomised study, the risk of an ipsilateral breast event at 12 years was 14.4% for the low-intermediate grade group (561 women) and 24.6% for the high grade group (104 women).11 Patients might have differing opinions on what constitutes an acceptable risk of an ipsilateral breast event.

Scoring systems 12-14 have been developed to predict the risk of local recurrence in an attempt to identify patients at low risk of recurrence who may be able to avoid WBRT and thereby guide adjuvant therapy recommendations (table 1). However, these scores are used variably in practice as they do not provide sufficiently precise estimates.

Table 1

Predictive scoring systems in DCIS [Online only]

View this table:

Does WBRT reduce overall or breast cancer specific mortality?

Although WBRT has been shown to decrease the risk of within-breast recurrence by around 50%, it has not been shown to improve breast cancer mortality.15 16 Five randomised controlled trials in women with DCIS showed that WBRT did not influence breast cancer mortality or overall survival (table 2). The EBCTCG patient-level meta-analysis reported a 10 year breast cancer mortality of around 4%3 and therefore a very large study would be required to show a modest reduction in breast cancer mortality from WBRT. Similarly, recent large population based longitudinal studies find insufficient benefit of WBRT in reducing breast cancer specific mortality at 10 and 20 years to warrant its use in all patients.16 17

Table 2

Randomised controlled trials of WBRT in DCIS summary [online only]

View this table:

[Online only] A recent study analysed 10 and 20 year breast cancer specific mortality using the Surveillance Epidemiology and End Results (SEER) data (18 registries, 108 196 women with DCIS). Invasive recurrence increased the risk of dying from breast cancer (hazard ration 18.1, 95% confidence interval 14.0-23.6; P<0.001), but the prevention of recurrence by WBRT did not diminish breast cancer specific mortality at 10 years.16 It is not possible to identify and account for the potential confounding factors in a study of this type, but these results suggest that the increased mortality risk associated with invasive recurrence is unlikely to be great enough to warrant WBRT.

Another large population based longitudinal study also used SEER data 17 to study breast cancer specific mortality after BCS alone and in patients who received BCS and WBRT. The study used a patient prognostic scoring model comprising clinical and pathological features for risk stratification and propensity scoring to address possible confounding. In this cohort of 32 144 women, breast cancer mortality rate was 0.9%. The 10 year breast cancer mortality rate was 1.8% in the WBRT group and 2.1% in the non-WBRT group (absolute difference, 0.3%; log-rank test, P=0.003; hazard ratio, 0.73; 95% confidence interval, 0.62 to 0.88). However, the hazard ratios depicting the apparent effect of WBRT for each of the defined prognostic groups had wide confidence intervals, and a causal relationship between WBRT and reduced breast cancer mortality cannot be confirmed.

Any small benefit derived from WBRT in breast cancer specific mortality, if this exists, must be appreciated in the context that patients with screen detected DCIS are much more likely to die of other causes than those related to breast cancer.17

Is ongoing research likely to provide relevant evidence?

We searched clinical trial registries and found three large studies that might shed light on some of the uncertainty around the use of radiotherapy in patients with DCIS. The two largest trials aim to identify low risk DCIS patients based on clinical and pathological factors and compare active surveillance with standard therapy (breast conserving surgery and WBRT) using 10 year rate of invasive local recurrence as an endpoint18 (table 3). These studies should help to elucidate the natural history of DCIS and how to identify patients with a low risk of invasive recurrence.

Table 3

New trials [online only]

View this table:

What to do in the light of the uncertainty

  • The benefit of WBRT in DCIS in many cases is small, and patients who wish to avoid WBRT can be supported and reassured in this decision.

  • Discuss the uncertainty over the risks and benefits of WBRT treatment with patients fully.

  • It is likely that a subset of patients does not need WBRT, but we have yet to develop the best way to identify this group.6

  • A reasonable approach is to risk stratify patients using one of the scoring systems in table 1. Table 4 lists clinical and pathological features shown to be associated with recurrence. Where possible, use shared decision making aids to help the conversation with patients.32 Offer counselling with specialist nurses and provide information leaflets that display all treatment options.

Table 4

Clinical pathological features found to be associated with recurrence

View this table:

What patients need to know

  • Ductal carcinoma in situ very rarely leads to death.

  • Most DCIS is treated with breast conserving surgery (BCS), often followed by whole breast radiotherapy (WBRT).

  • WBRT reduces the risk of recurrence, but WBRT does not reduce the risk of dying from breast cancer or improve overall survival.

  • You should expect your doctor to advise you on the likely benefits and risks of radiotherapy, taking into consideration the severity of your disease and any other health problems, and accepting that there is some uncertainty about the benefits of treatment.

  • Because of this uncertainty, you might wish to explore what type of treatment is best for you based on your personal risk tolerance and life expectancy.

[Online only] Recommendations for future research

  • Development of better predictive markers/tools to identify a group of patients in whom WBRT can be safely omitted

  • Explore how current evidence is understood by clinicians and delivered to patients to reduce geographical variations in the proportion of patients being offered WBRT

  • Explore how patients feel about making decisions around WBRT

Education into Practice

  • How has reading this article changed the way you might approach discussions of radiotherapy with patients with DCIS?

  • How might you better support patients who have received a diagnosis of DCIS?

How patients were involved in the creation of this article

A draft manuscript was reviewed by representatives of ICPV (http://www.independentcancerpatientsvoice.org.uk/). They were happy with the overall manuscript but had specific statements about what a patient can expect from their doctor and this was addressed in the “what patients need to know” box. A patient with DCIS kindly reviewed this paper. She endorsed the uncertainty around appropriate treatment for DCIS and that medical professionals must recognise that patients have different personal risk tolerances. We have emphasised this and suggest that doctors discuss the risk and benefits of WBRT and assist patients in making a shared decision.

Footnotes

  • This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series advisers are Sera Tort, clinical editor, and David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at uncertainties{at}bmj.com

  • Provenance and peer review: Commissioned, based on an idea from the author; externally peer reviewed.

  • Competing interests: We have read and agreed to the BMJs conflict of interest policy. JB was a clinical editor at BMJ from 2015 to 2017.

View Abstract

Log in

Log in through your institution

Subscribe

* For online subscription