You’ve been looking at patients who have had breast conserving therapy for ductal carcinoma in situ, can you tell me what you were trying to do with this new gene test?
Ductal carcinoma in situ is a non-invasive cancer and it’s associated with a very high rate of survival. The treatment is recommended because some women will go on to recur. Most women will have breast conserving surgery followed by radiation treatment but guidelines recommend that breast conserving surgery alone, without radiation, is an option for women at low risk of recurrence. The challenge is that traditional clinical factors and the pathological features of DCIS do not reliably help clinicians identify those individuals at low risk of recurrence. So we know currently many women with DCIS receive unnecessary treatment or over-treatment and many do not have sufficient treatment or are under-treated. This is a biomarker assay; it’s 12 genes of the 21 genes that comprise the Oncotype-DX recurrence score which is prognostic in women with early invasive cancer. These 12 genes have been shown to be associated with the risk of recurrence in women with DCIS treated with breast conserving surgery alone.
Now you’ve done a study with substantial numbers of patients, can you tell me exactly what you did? What was the protocol?
Yes. So, the initial study in the ECOG E5194 analysis showed that this multi-gene assay is associated with recurrence. But the individuals in that study were highly selected for this prospective cohort study and it remained unknown if the DCIS score would be prognostic in a more general population of women with DCIS. So we established a population based cohort of women with pure DCIS diagnosed in Ontario from 1994 to 2003. We went through a very rigorous process to identify women treated with breast conserving surgery alone. We did a pathology review of their slides and identified those with clear margins; that’s the study cohort – 571 women. We then evaluated the DCIS score as an independent predictor of local recurrence in this population.
And what numbers come out of this?
We found that in this population women who had a low risk score had a significantly lower risk of recurrence at ten years compared to those in the intermediate and high risk groups. This was highly statistically significant. Individuals, the DCIS score was associated with a hazard ratio of about 2 for every 50 point increase but the DCIS risk group, as was previously defined, low, intermediate and high, the individuals in the low risk group had about a 12% risk of recurrence at ten years compared to 25-30% for those in the intermediate and high risk group.
Now how does that rather precise molecular signature of risk compare with the classical ways of assessing risk?
What’s very exciting about this is this is the first multi-gene assay in DCIS to provide individualised estimates of risk. So in the future a woman and her physicians can better understand her risk of recurrence after treatment by breast conserving surgery alone. This applies to the average woman with DCIS, not one with many high risk features. But the majority of women fall into the category of average risk where we’re really uncertain as to whether or not radiation is indicated. This assay provides a more accurate assessment of recurrence risk and that can better inform clinicians and patients of the risk of recurrence and they then can have a more informed discussion about the potential benefits of treatment such as radiation and even Tamoxifen.
And to get some idea of the efficiency, the usefulness, of this new addition to the armoury of ways of assessing risk, how much radiation do you think you could, or how many cases of radiation, could you avoid?
That’s difficult to tell; it’s beyond the scope of this study. It really depends on the population and the utilisation of radiation. But we start by having a more accurate and individualised estimate of recurrence risk and then that can better inform the physician-patient discussion on the potential benefits or even the need for additional treatment.
So how would you like to see doctors applying this sort of information and this new test?
DCIS should be treated and is often treated in a multidisciplinary setting with surgeons, radiation oncologists and medical oncologists. Individuals that are at average risk for whom we consider omitting radiation treatment, this test can provide a risk estimate, an individualised risk estimate. Then that can be taken to the patient and a more informed discussion about the potential benefits of radiation treatment, or even the need for radiation treatment, will then depend on the individual’s preferences as well as her risk and other comorbid conditions she might have. It really does help provide a better estimate of risk and a better understanding of the potential need and benefits of treatment.
And how easy is it for the multidisciplinary team to come to the sort of consensus about what needs to be done?
Again, that’s beyond the scope of this study and that for future consensus conferences and treatment guidelines will help guide us in the integration of the DCIS score into clinical practice.
So could you summarise for me what you’ve achieved with this study?
The biggest achievement of this study is to confirm that the DCIS score is predictive of recurrence in a general population cohort of women with DCIS who were treated with breast conserving surgery alone.
And what doctors should take home from all of this?
Doctors should take home that this assay can help provide individualised estimates and help them and their patients better understand risks and potential benefits of future treatment. Hopefully this can help towards the goal of reducing over-treatment and reducing under-treatment for women with DCIS in the future.