Researchers leading the LORD trial of active surveillance for ductal carcinoma in situ (DCIS) described early results as “reassuring” in a presentation to the 15th European Breast Cancer Conference (EBCC15) in Barcelona (Abstract 2LBA).
People diagnosed with DCIS have abnormal cells inside the milk ducts of their breast, but because these cells have not spread into the surrounding breast tissue, DCIS is not invasive breast cancer. DCIS can develop into invasive breast cancer over time, but research suggests that about four out of five cases will never become invasive or life-threatening. DCIS is typically treated with surgery and sometimes with radiotherapy or hormone therapy. Researchers launched the LORD trial (ClinicalTrials.gov identifier NCT02492607) to evaluate whether patients with low-risk DCIS can be safely monitored with regular check-ups instead of having immediate surgery.
The research was presented at EBCC15 by Jelle Wesseling, MD, PhD, of the Netherlands Cancer Institute and Leiden University Medical Center. He said, “For decades, DCIS was framed as ‘early-stage breast cancer’. As a result, it has almost always been treated in the same way as breast cancer. But if most DCIS will never become dangerous, an important question arises: are some women receiving more treatment than they need? As a doctor, I am guided by the principle ‘first, do no harm’. My motivation for starting the LORD trial was simple: to help make care safer and more balanced. We wanted to find out whether carefully selected women with low-risk DCIS can be safely monitored with regular check-ups, known as active surveillance, instead of having immediate surgery. The goal is to avoid unnecessary treatment without putting women at risk.”
Findings From LORD
Dr. Wesseling presented data on 1,423 patients who have been taking part in the trial for around 2 years on average. The patients were being treated for low-risk DCIS (meaning grade 1 or 2 DCIS that was picked up via breast screening) at approximately 60 hospitals across the Netherlands.
The trial began in 2017, and the first 73 patients to join the trial were randomly assigned to receive either standard treatment (surgery to remove the DCIS) or active surveillance (close monitoring with treatment initiated only if needed). At that point, following feedback, the trial was adapted to allow patients to choose between the two options, with around three-quarters opting for active surveillance (n = 1,025 vs n = 330 choosing immediate treatment).
Out of the 363 patients treated with immediate surgery, examination of the breast tissue that had been removed revealed that 29 patients had signs of invasive breast cancer at the start of the trial.
A further 4 patients out of the 363 who received surgery at the start of the trial have since been diagnosed with invasive breast cancer.
Out of the 1,060 patients who have been having active surveillance, 63 have been diagnosed with invasive breast cancer. The study has now been stopped, as per its protocol, which stated that the trial should not continue once 60 patients had been diagnosed with invasive breast cancer.
Putting together all the patients who have been diagnosed with invasive cancer so far, there are 33 out of 363 in the standard treatment group (9%), compared to the 63 of 1,060 (6%) in active surveillance group. Researchers found that the tumors diagnosed in patients having active surveillance were slightly larger on average (6 mm compared to 9 mm), but they were not more aggressive.
Dr. Wesseling said: “For women with low-risk DCIS, these interim results are reassuring. There is currently no indication that active surveillance leads to worse early outcomes compared with immediate surgery. It’s important to explain that active surveillance does not mean withholding treatment; it does mean that patients are closely monitored and that surgery remains possible at any time. More broadly, this study contributes important evidence to the discussion about reducing overtreatment in breast cancer care. However, longer follow-up will be crucial before making changes to existing guidelines.”
The researchers are continuing to follow up with all patients who are taking part in the trial to monitor the safety of the two approaches in the long term. They are also looking in more detail at which patients develop invasive cancer to try to understand which women can safely avoid immediate surgery.
DISCLOSURE: For full disclosures of the study authors, visit cm.eortc.org/cmPortal/Searchable/ebcc15.
