Safe omission of post-surgery radiotherapy for patients with low DCIS score

The E4112 clinical trial demonstrated a comparable ipsilateral breast event (IBE) rate for patients with a low DCIS score (DS) who were only treated with a wide local excision (WLE) as for intermediate/high DS patients who were treated with WLE and radiation. As such, this prospective trial provides evidence that it is safe to omit radiotherapy after surgery in DCIS patients with a low DS and advocates for its application in those with intermediate/high DS.

Nearly all women with Ductal Carcinoma In Situ (DCIS), a non-invasive form of breast cancer, will have their cancer successfully removed. Still, some women have a high risk of disease recurrence, or progressing to invasive breast cancer. Most patients with DCIS undergo breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT), which is intended to reduce the likelihood for a recurrence. About a quarter of patients with DCIS undergo mastectomy instead. However, there is an increasing consensus on the fact that this treatment strategy puts an unnecessary treatment burden of a large proportion of women. In this, personalised diagnostic tools to predict the risk of recurrence or progression may prevent excessive treatment for some patients. Advanced diagnostics such as magnetic resonance imaging (MRI) and gene-expression profiles are potentially useful to guide treatment decisions in patients with DCIS. Based on this rationale, the E4112 clinical trial assessed the potential of bilateral MRI coupled with a DCIS gene profile to guide treatment decisions in patients with DCIS. Previously reported results from this trial indicated that MRI could help to identify patients who could opt for the less intensive BCS instead of a mastectomy. At SABCS 2023, a pre-planned analysis of the incidence of ipsilateral breast events (IBE) at five years was reported.

Methods

The trial enrolled women with core-biopsy-proven unilateral DCIS, excluding cases with microinvasion, suitable for BCS based on conventional imaging, no prior history of invasive breast cancer or DCIS and no use of anti-oestrogens in the last three months. All registered patients underwent breast MRI, and those eligible for wide local excision (WLE) proceeded with resection after follow-up biopsies. Patients with a low RT DCIS score (DS < 39) were advised to omit RT, while those with intermediate/high DS (≥39) were recommended to receive it. For this trial, IBE was defined as a recurrence, either DCIS or invasive, in the ipsilateral breast post-WLE.

Results

Out of the 339 evaluable women who were included in the previously reported primary analysis, 171 (50.4%) had a WLE with free surgical margins and had a DS result available (ITT population). Of note, 7 out of the 82 patients with a low DS underwent RT, and 5 out of 89 patients with intermediate/hight DS declined RT. Consequently, the adherence to DS-based RT recommendations was 93%.

After a median follow-up of 5 years from the WLE, the ITT population (n=171) experienced a total of eight IBE events (4.8%). The 5-year IBE rates were similar for participants with a low DS (5.1%) and with an intermediate/high DS (4.5%). Similar outcomes were observed in patients adhering to their DS-based RT recommendation (n=159), with eight IBE events in total (5.2%) and comparable 5-year IBE rates for low DS (5.5%) and intermediate/high DS (4.8%). Stratification by age did not alter these results. Among women aged <50 years (n=33), the IBE rate was 6.7% for low DS and 5.6% for intermediate/high DS. There were two invasive IBE events, one in the RT and one in non-RT groups. Among women aged ≥50 years (n=138), the IBE rate was 4.7% for low DS and 4.3% for intermediate/high DS. There were three IBE events in both RT and non-RT groups, one invasive in each group.

Conclusion

Despite the limited sample size, the findings of this prospective study offer reassurance that the IBE rate is similar for DS low patients treated with WLE alone as for intermediate/high DS patients treated with WLE and radiation. As such, this trial provides evidence supporting the omission of RT after surgery in DCIS patients with low DS, and its use in patients with intermediate/high DS.

Reference

Khan S, Romanoff J, Gatsonis C,et al. Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112. Presented at SABCS 2023; Abstract GS03-01.