Study reveals short term safety of active monitoring for ductal carcinoma in situ

The early results of the Comparing an Operation to Monitoring with or without Endocrine Therapy (COMET) study suggest women and their doctors may consider active monitoring as a safe, less-aggressive alternative for treating low-risk DCIS. Researchers have believed that many women diagnosed with DCIS do not benefit from treatment, but this has not been put to the test in a clinical trial.

Study results are being presented Dec. 12 at the San Antonio Breast Cancer Symposium by co-principal investigator E. Shelley Hwang, M.D., of the Duke Cancer Institute, who is vice-chair of research in Duke's Department of Surgery. The study is simultaneously published in the Journal of the American Medical Association (JAMA).

Often called "stage-zero breast cancer," or "precancer," DCIS is identified by abnormal cells within the milk ducts. It doesn't always become the invasive type of cancer that can spread outside the breast. DCIS accounts for roughly one in five new breast cancer cases in the U.S., affecting more than 50,000 women every year.

Currently, nearly all women with DCIS are treated with surgery, and as many as one-third undergo a mastectomy, which can result in long-term symptoms and altered body image.

Active monitoring is an alternative to surgery and radiation that involves performing mammograms routinely to check for early changes.

"Many women wonder -- 'Do I really need to do this to myself?' -- when they're faced with surgery and possibly radiation to remove DCIS," Hwang said. "These early results from our study give us reassurance that active monitoring is safe in the short term and that the cancers that are diagnosed during active monitoring are detected at an early stage."

For the COMET study, Hwang and the research team -- including co-principal investigator Ann Partridge, M.D., of Dana-Farber Cancer Institute -- enrolled nearly 1,000 women ages 40 and up.

After biopsy and confirmation of DCIS, study participants were randomized into two treatment groups: the current standard of care involving surgery and radiation, or the alternative of active monitoring. Most women in both groups also received endocrine therapy to block the estrogen hormone, which often fuels cancer cells.

At two years, the rate of invasive cancer in women in the surgery group was 5.9%, compared to 4.2% in women who did active monitoring. Hwang said the higher rate of invasive cancers found among the group receiving traditional treatment could be the result of "upstaging," in which invasive cancer is identified in patients diagnosed with DCIS at the time of surgery.

"We noted there were fewer cancers diagnosed in those patients who had active monitoring, and we feel that part of this was due to the hormone blocking treatment that many of them had," Hwang said. "Although this was optional on the study, over 70% of women combined active monitoring with endocrine therapy, suggesting that this may be an important part of active monitoring in the future for women with DCIS."

Both selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have been shown to reduce the incidence of invasive cancer by approximately 50%, with plausible mechanisms being either prevention of DCIS progression or reversal of invasive cancer.

"These early results are provocative and potentially exciting for patients, but we clearly need more long-term follow-up," Hwang said. "If these results hold up over time, most patients who have this type of low-risk disease will have the option of avoiding invasive treatments. That would be a complete change in how we care for these patients and think about this disease."

In a separate analysis, Hwang and Partridge co-led an additional study measuring patient-reported outcomes from both groups involved in the COMET study.

"The women in the study also told us in surveys how they felt over time," said Partridge, interim chair of Medical Oncology at Dana-Farber Cancer Institute. "Fortunately, the overall health-related quality of life, anxiety, depression, worries, and symptom trajectories were comparable regardless of the treatment received during two years of follow-up."

In addition to Hwang, study authors from Duke include Thomas Lynch, Marc D. Ryser, Lars Grimm, Jeffrey Marks, Rachel Factor, and Yan Li. 

The COMET study was sponsored by Alliance Foundation Trials and received funding support from the Patient-Centered Outcomes Research Institute (PCS-1505-30497), the Breast Cancer Research Foundation, and Rising Tide Foundation.