With right-sizing treatment an aim of many treatment approaches in breast cancer today, ductal carcinoma in situ (DCIS), as well as its overtreatment, has become a potential target of change. Which patients, however, might safely forgo the current recommendations and be safely followed with active monitoring? This issue was tackled at the 2025 Miami Breast Cancer Conference by Alastair M. Thompson, BSc (Hons), MBChB, MD, FRCS (Ed), the Olga Keith Weiss Chair of Surgery at Baylor College of Medicine in Houston.
Dr. Thompson noted that for some prostate cancer, cervical neoplasia, small thyroid cancers, and small renal cancers—considered low-risk malignancies—active monitoring may be a viable alternative to surgery. “The question that arises in breast cancer is whether every patient with DCIS needs surgery, or whether active monitoring might also work,” he said.
“The question that arises in breast cancer is whether every patient with DCIS needs surgery, or whether active monitoring might also work.”— ALASTAIR M. THOMPSON, BSc (HONS), MBChB, MD, FRCS (Ed)
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DCIS is a very heterogeneous condition. It may remain stable as an indolent process within the breast, or it may progress to invasive disease. A pivotal study conducted in 2015 in the United States showed that grade 1 DCIS carried a 5% risk of progression to invasive breast cancer at 10 years, whether patients were treated with surgery or active monitoring. The risk increased by grade, with the 10-year risk reaching 19% for grade 3 disease that was actively monitored.1
Difficulty in Defining Low Risk
The definition of “low risk” varies by country; therefore, the incidence of low-risk disease within the DCIS population also varies, from 8% in the United Kingdom to 40% in Japan. In general, the risk of invasive disease is more likely for patients who are young or who have palpable or extensive disease, comedo necrosis, and high-grade disease.2 Validated genetic signatures can also be informative, including Oncotype DX Breast DCIS Score and DCISionRT. Although all these factors are helpful, Dr. Thompson said, “the problem” is the lack of agreement among pathologists as to the level of the tumor grade and the presence of comedo necrosis. “This makes it tough, if we are asking patients to consider active monitoring, and we can’t standardize our grading or agree whether comedo necrosis is present,” he noted.
COMET Findings
Four large international trials are evaluating surgery vs active monitoring. “In due time,” he said, they will each produce patient-reported outcome data and allow for a meta-analysis. The first to report findings is COMET, for which Dr. Thompson is a co-investigator.3
COMET is a prospective, randomized, noninferiority trial comparing 997 patients who received guideline concordant care or active monitoring. Patients are aged 40 or older; they have low-risk DCIS (grade 1 or 2) and no palpable mass and are allowed to have comedo necrosis (because of interpathologist variations). When the extent of DCIS exceeds 4 cm, biopsies from two sites are required to show all sites to be low-grade disease.
COMET is designed to answer whether active monitoring is safe and acceptable to patients suitable for breast conservation. The primary outcome at 2 years is the comparison of invasive cancers with active monitoring compared with guideline-concordant care (surgery and potentially radiation therapy after lumpectomy). Endocrine therapy could be received by patients in either arm.
The findings at 2 years were reassuring to patients who did not undergo surgery, according to Dr. Thompson. Outcomes in the active monitoring group were noninferior to those who received surgery, radiotherapy or other guideline-concordant treatment, with 2-year rates of invasive cancer of 4.2% (for active monitoring) and 5.9%, respectively, a nonsignificant difference of 1.7%. Furthermore, patient-reported outcomes were similar, with general health scores relatively stable and comparable to population norms.
“At the 2-year mark, the bottom line is that active monitoring does appear to be safe, and for the patients in the trial, it was acceptable,” stated Dr. Thompson. “Like any good trial, this raises many questions: How do we establish, on an individual patient basis, low-risk DCIS, and to what extent is active monitoring actually safe long term?”
It is possible, he acknowledged, that COMET’s results could have been affected by the receipt of endocrine therapy by 70% of the active monitoring arm (similar to the guideline-concordant care arm). Furthermore, minimum follow-up was short—2 years, as required by protocol—though the mean follow-up was 3 years; some have suggested that at least 5 years is necessary for understanding the outcomes of treatment in DCIS. Additionally, in COMET the actively monitored patients underwent mammography every 6 months, not annually as in most trials; after 5 years, patients will return to annual mammography. “The question now is whether COMET is going to change our practice or just inform our practice,” Dr. Thompson said.
State of Active Monitoring in DCIS
Dr. Thompson shared his take on the current state of low-risk DCIS management:
- Active monitoring for low-risk DCIS is safe, at least in the short term.
- Active monitoring is acceptable to patients, at least in the COMET trial.
- Longer follow-up of COMET will be important.
- Results are awaited for trials being conducted in the United Kingdom, the Netherlands, and Japan. They will need to be pooled together with COMET for a meta-analysis, which would provide more confidence in this as a global approach.
- Active monitoring is not an optimal strategy for all patients with DCIS, but it is certainly appropriate for some low-risk patients.
DISCLOSURE: Dr. Thompson reported no conflicts of interest; his spouse is employed by Eli Lilly and Company.
REFERENCES
1. Sagara Y, Mallory MA, Wong S, et al: Survival benefit of breast surgery for low-grade ductal carcinoma in situ: A population-based cohort study. JAMA Surg 150:739-745, 2015.
2. van Seijen M, Jóźwiak K, Pinder SE, et al: Variability in grading of ductal carcinoma in situ among an international group of pathologists. J Pathol Clin Res 7:233-242, 2021.
