Active monitoring of DCIS shows promise in short-term study

Abstract

Early results from the first study comparing active monitoring to surgery for patients with low-risk ductal carcinoma in situ (DCIS) support the short-term safety of active monitoring.

Researchers released the 2-year findings from a prospective, randomized clinical trial known as the Comparing an Operation to Monitoring With or Without Endocrine Therapy (COMET) study. Results showed that the rate of invasive cancer in both groups was low, but patients who had surgery (or guideline-concordant care) for DCIS had a slightly higher rate of invasive cancer than the group that underwent active monitoring. Although the study is a preliminary analysis, investigators are encouraged by the findings.

“I don’t think we have enough long-term data yet to offer active monitoring to DCIS patients, because two years is pretty short, but if these results are supported and durable at five years, we may be able to start offering it as a possible option,” says coprincipal investigator Shelley Hwang, MD, MPH, who is the vice-chair of research in the Department of Surgery at the Duke Cancer Institute in Durham, North Carolina. “The results are very provocative in terms of turning the assumption that we’ve always had on its head, and that’s why it’s such an important study—because it challenges dogma.”

Dr Hwang and her colleagues presented the COMET study results in December 2024 at the San Antonio Breast Cancer Symposium. Findings were concurrently published in the Journal of the American Medical Association (doi:10.1001/jama.2024.26698).

The trial enrolled 995 women aged 40 years or older with a new diagnosis of hormone receptor–positive grade 1 or 2 DCIS without invasive cancer. Participants were enrolled at 100 US Alliance Cooperative Group clinical trial sites from 2017 to 2023. They were randomized, with 484 participants assigned to active monitoring and 473 assigned to receive surgery. Participants will be followed for 10 years.

The main purpose is to determine if DCIS, which is also called stage 0 breast cancer, needs to be treated with surgery in every patient.

“We’ve never really put our treatments to that sort of test because everyone has been really fearful of doing anything less,” Dr Hwang says.

The study excluded patients who were hormone receptor–negative as well as those who had a physical finding such as a lump, bloody discharge, or changes in the skin. Patients were allowed to enter the study regardless of the size of their DCIS.

Active monitoring, with or without endocrine therapy, included follow-up breast imaging along with a physical examination every 6 months. Although endocrine therapy was not mandatory, more than 70% chose to receive it. Guidance-concordant care was surgery with or without radiation therapy and with or without endocrine therapy. This group also had 6-month follow-ups.

The primary outcome of the preliminary analysis was the 2-year cumulative risk of an invasive breast cancer diagnosis in the DCIS-affected breast.

As the study continues, researchers will analyze how many biopsies were performed on patients with active monitoring based on mammographic findings and how many biopsies were benign. They also will analyze the number of women who remained on endocrine therapy for 5 years.

The median age of the participants was 63.6 years in the surgery group and 63.7 years in the active-monitoring group. Participants included Black (15.7%), White (75%), Hispanic (7%), and Asian women (4.8%).

Because patients with DCIS have an excellent prognosis after surgery, some have questioned why this approach needs to change, Dr Hwang notes. In truth, DCIS is not as worrisome as invasive cancer, and this has prompted the question, for her and others, whether these patients would do just as well without treatment.

The distinction between invasive and in situ breast cancer is frequently unclear to the newly diagnosed patient with breast cancer, says Jennifer Gass, MD, a professor of surgery and obstetrics and gynecology at Brown University (Providence, Rhode Island), who did not participate in the study. “We didn’t develop different protocols on how to treat it [DCIS] because it was viewed as a precursor lesion rather than as a risk factor for future invasive cancer,” she says. “Twenty or thirty years ago, finding a precursor lesion and preventing it from progressing was thought to be critical because invasive breast cancer had a significant risk of mortality. But fast-forward to 2017, when the study was launched, and we’re in a whole different era of breast oncology where curative therapy for stage 1 and 2 breast cancer is the expectation. We don’t know how long non-invasive breast cancer can simply be observed, and that’s the impetus for this study.”

The authors chose to review the results at 2 years to ensure that it was safe for women to remain on active monitoring.

“We didn’t want patients to continue on this study if it turned out we were wrong and there was a high risk they would develop cancer,” Dr Hwang says. “It was important to get that initial safety signal.”

The 2-year cumulative rate of invasive cancer in the DCIS-affected breast was 5.9% in the guideline-concordant care group and 4.2% in the active-monitoring group. These results show that after 2 years, active monitoring apparently resulted in similar outcomes in comparison with guideline-concordant care for patients with low-risk DCIS.

The aforementioned results were in the intention-to-treat analysis. In the per protocol analysis (excluding patients who were randomized but did not get the treatment that was required of their group), the invasive cancer rate was 8.7% for the guideline-concordant care group and 3.1% for the active-monitoring group.

In the preliminary primary analysis, the median follow-up was 36.9 months. At that time, 346 patients had surgery for DCIS: 264 in the guideline-concordant care group and 82 in the active-monitoring group. Forty-six participants were diagnosed with invasive cancer: 19 in the active-monitoring group and 27 in the surgery group.

Because women in the active-monitoring group received endocrine therapy right after they were diagnosed, whereas the surgery group did not receive it until after surgery, it is possible that the hormone treatment may have prevented more cancers in the active-monitoring group, Dr Hwang notes. She cautions, however, that more study is needed in this area.

“We did a concurrent quality-of-life outcome study, and it did not show that women on the monitoring arm were any more anxious or worried about the disease than women who had surgery right away,” Dr Hwang adds.

“These data show that DCIS is not an emergency,” Dr Hwang says. “It doesn’t turn into cancer overnight. Patients have time to make well-informed treatment decisions.”

However, she lists a few caveats. First, the study did not include all grades of DCIS and focused only on those patients with low-risk disease. She cautions that the findings do not imply that all women with DCIS should be actively monitored. Rather, if the results are confirmatory after 5 years, active monitoring should be offered as a safe alternative for some women.

Dr Gass agrees. “I usually bring up this study to let patients know how favorable the disease is, but I haven’t had any patients who haven’t wanted treatment.”

Dr Hwang points out that, in general, approximately 30% of women with DCIS choose mastectomy, even though the current treatment guideline is lumpectomy with radiation. As a result, many women may be undergoing an unnecessary surgery.

Dr Gass wants to see the long-term data. She notes the possibility that endocrine therapy may be suppressing cancer growth in the active-monitoring group. If so, an invasive cancer may be found in some participants of that group after 2 years—one that could have been detected earlier had they undergone surgery after their initial diagnosis.

“The researchers are trying to evaluate if, with active monitoring, we can safely find the women who are going to progress to invasive cancer and cure them at the same rate as with guideline-concordant care. If we can do that, it has the potential to be a huge paradigm shift,” she says.

Dr Gass also would like to see more information on the patient eligibility criteria based on breast calcification size.

“A needle sample of a 10-centimeter spot versus a 10-milimeter spot is totally different,” Dr Gass says. “A sample is part of a larger process, and there’s an underlying concern that there could be an invasive cancer that we don’t find that needs attention.”

The researchers’ goal is to be able to predict which patients’ DCIS will progress to invasive cancer, and they are making some progress. Through the Human Tumor Atlas Network, Dr Hwang and her colleagues have developed a biomarker that appears to predict which patients with DCIS who undergo surgery are more likely to develop invasive cancer. They hope to develop a similar predictive biomarker for women with DCIS who are actively monitored.

“A biomarker would really help promote active monitoring as a rational, maybe even preferable, way of taking care of patients with this disease,” she says.