Patients with low-risk ductal carcinoma in situ (DCIS) who omitted adjuvant radiotherapy after breast-conserving surgery had comparable five-year outcomes to those with high-risk DCIS who received adjuvant radiotherapy, according to results from clinical trial E4112 presented at the San Antonio Breast Cancer Symposium, held December 5-9, 2023.
Almost all women with DCIS – a non-invasive form of breast cancer – will have their cancer successfully removed, but some women will have a high risk of the disease coming back or progressing to invasive breast cancer.”
Seema A. Khan, MD, professor of surgery and the Bluhm Family Professor of Cancer Research at Northwestern University’s Feinberg School of Medicine and Lurie Comprehensive Cancer Center
She explained that most patients with DCIS undergo breast-conserving surgery followed by adjuvant radiation therapy, which aims to reduce the chance of the disease coming back as DCIS or invasive breast cancer. About a quarter of DCIS patients undergo a mastectomy.
“There is a growing realization that DCIS carries an unnecessary treatment burden for many women,” Khan noted. “Using personalized diagnostic tools to predict risk of relapse or progression may prevent overtreatment for some patients.”
Khan and colleagues conducted the E4112 clinical trial to assess the potential of bilateral magnetic resonance imaging (MRI) combined with a DCIS gene profile to guide therapy for patients with DCIS. Previously reported results from that trial showed that MRI could help identify patients who might choose less invasive breast-conserving surgery instead of mastectomy, Khan noted.
The most recent analysis aimed to determine whether some of these patients who underwent breast-conserving surgery based on MRI results could also be safely forgone from subsequent radiation therapy based on a DCIS gene expression profile. This approach could help reduce treatment in patients whose DCIS carries a low risk of recurrence, he explained.
The analysis included 171 patients with DCIS who underwent breast-conserving surgery and whose tumor tissue was determined using the Oncotype DX Breast DCIS Score test.
The Oncotype DX Breast DCIS Score is a laboratory test that examines the expression levels of cancer-related genes in DCIS tissue. The test results are reported as a score between zero and 100, with higher scores associated with higher expression of cancer-related genes and a greater likelihood of the disease recurring in the same breast, either as DCIS or invasive cancer.
In this study, patients who scored lower than 39 were considered to have low-risk DCIS and were eligible to skip adjuvant radiotherapy, while patients with a score of 39 or higher were recommended to receive adjuvant radiotherapy.
Adherence to treatment recommendations based on the score was 93%: 75 of 82 patients with low-risk DCIS elected to forgo adjuvant radiotherapy and 84 of 89 patients with high-risk DCIS elected to undergo adjuvant radiotherapy.
At a median follow-up of five years after surgery, 5.1% of 82 patients with low-risk DCIS and 4.5% of 89 patients with high-risk DCIS experienced disease recurrence in the same breast as the primary DCIS. Similar results were found when comparing only those patients who complied with the score-based recommendations: 5.5% of 75 patients with low-risk DCIS who skipped radiation therapy experienced disease recurrence, compared with 4.8% of 84 patients with high-risk DCIS who received radiotherapy. The differences were not statistically significant or affected by patient age in either analysis.
“Our results show that the Oncotype DX Breast DCIS Score was an effective tool for stratifying patients for adjuvant radiation therapy after breast-conserving surgery. Women who skipped radiation based on this score did not have an excess risk of recurrence in the same breast during the five-year follow-up period,” Khan said. “These findings reveal a new approach to guide treatment decisions by identifying which patients can benefit from radiation therapy and which patients can safely forego it.”
Combined with previously reported data from the trial, the results demonstrate the potential of MRI and the Oncotype DX Breast DCIS Score to guide surgery and adjuvant therapy, respectively, for patients with DCIS, he added.
Limitations of the study include the short follow-up time, small sample size, and non-randomized design.
Study E4112 was designed and conducted by the ECOG-ACRIN Cancer Research Group with support from the National Cancer Institute of the National Institutes of Health. Other collaborative groups involved were the Alliance for Clinical Trials in Oncology, NRG Oncology and the SWOG Cancer Research Network. Khan declares no conflict of interest.
