DUCTAL CARCINOMA IN SITU (DCIS) is a noninvasive form of breast cancer that develops in the lining of the breast duct. Often called stage 0 disease, DCIS itself is not life-threatening and often does not progress, but it can potentially spread and lead to invasive breast cancer. Because of that potential danger, most people diagnosed with DCIS receive treatment to reduce their risk, but some experts fear many patients are being overtreated.

New research presented Dec. 12 at the San Antonio Breast Cancer Symposium highlighted ways select people with DCIS can skip portions of treatment without increasing their breast cancer risk. One study found endocrine therapy can reduce recurrence among people who opt not to get radiation, while another found certain patients can select active monitoring instead of immediate surgery without increasing their risk.

Endocrine Therapy for People Who Forgo Radiation

The main treatment for DCIS is breast-conserving surgery, also called a lumpectomy, to remove the abnormal cells, according to National Comprehensive Cancer Network guidelines. Most people receive radiation after surgery to reduce their recurrence risk, but radiation may not be needed for a small group of patients who have a low chance of the disease returning. People diagnosed with grade 1 or 2 DCIS that was 2.5 centimeters or smaller and who had no cancerous cells in the 3-millimeter outer edge of the tissue removed during surgery have the option to forgo radiation.

But how can those who don’t opt for post-surgical radiation further reduce their recurrence risk? Some research suggests endocrine therapy could limit the chance of cancer returning, but the evidence has been unclear. “In this setting, most modern studies have left the use of endocrine therapy at the discretion of the treating physician and the patient without mandating its use, and as a result, practice is highly variable,” said Jean L. Wright, a radiation oncologist at Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill.

Wright and her colleagues investigated if a form of endocrine therapy called tamoxifen could reduce recurrence risk in this population. Using data from two prior studies, researchers looked at outcomes for 878 people with DCIS who underwent breast-conserving surgery and did not receive subsequent radiation. Of these participants, 43% took tamoxifen following surgery. After 15 years of follow-up, 117 people had a cancer recurrence in the same breast. Researchers found the 15-year recurrence risk for people treated with tamoxifen after surgery was 11.4%, compared with 19% for those who did not take endocrine therapy. When researchers analyzed subgroups based on age, race and disease characteristics, they continued to see lower recurrence rates with tamoxifen use “across all subsets of patients, suggesting a broad benefit,” Wright said.

While research has yet to assess tamoxifen’s impact on survival, Wright said these findings can help people as they consider post-surgical options for reducing their chance of recurrence. “The decision to recommend endocrine therapy in the setting of radiation omission should still be a shared-decision process, but I think we now have much clearer data to present to our patients who are considering forgoing radiation therapy,” she said.

Wright noted radiation and endocrine therapy have vastly different durations and side effects. While radiation occurs over one to five weeks, endocrine therapy is recommended for a five-year period. Radiation can cause fatigue, hair loss, skin changes and swelling, among other toxicities, while endocrine therapy’s side effects include hot flashes, night sweats and vaginal dryness.

Wright said these findings should allow people with low-risk DCIS to be better informed when selecting which option works best for them. “It’s always important to engage the patient in these types of decisions,” she said. “It would be very reasonable for patients to choose one or the other based on the information that we now have.”

Active Monitoring in Low-risk DCIS

While some cases of DCIS will progress to invasive breast cancer, many will not and pose no danger to the person’s health. With current standard treatment calling for surgery, many people with DCIS are overtreated for something that would have never developed into cancer and have to deal with the physical and mental impact of surgery.

To avoid overtreatment, researchers are investigating a strategy known as active monitoring, where patients forgo treatment until the disease shows signs of progression. The strategy has gained prominence in prostate cancer, but a new study, which was simultaneously published in JAMA, suggests it also may be an option for people with DCIS.

In a clinical trial, 995 people with grade 1 or 2 HR-positive, HER2-negative DCIS were randomly assigned to either start active monitoring or receive standard care, which consisted of surgery to remove the cancer with the option for subsequent radiation. Participants in the active monitoring group received a mammogram of the affected breast every six months, along with an annual mammogram of both breasts, and they had the option to receive surgery if the cancer showed signs of progression. People in both groups could choose to start endocrine therapy.

After two years, 5.9% of people who had standard care were diagnosed with invasive cancer in the same breast, compared with 4.2% of the active monitoring group. Among participants who received endocrine therapy, 7.15% of the standard care group developed cancer, compared with 3.21% of the active monitoring group.

Researchers also looked at quality of life in a separate analysis simultaneously published in JAMA Oncology. Participants completed questionnaires that assessed their quality of life, anxiety, depression and level of fear of recurrence at the start of the trial. They filled out the same questionnaire six months and one year later and then annually. Researchers found participants reported stable levels of health-related quality of life throughout the first two years. Additionally, there were no significant differences between the active monitoring and standard care groups in anxiety, depression or level of worry about cancer.

E. Shelley Hwang, a study author and a surgical oncologist at the Duke Cancer Center in Durham, North Carolina, called the study results “provocative” and “encouraging” but said more follow-up is needed. Researchers will analyze outcomes after five, seven and 10 years. “If these results are durable, then I believe these will be practice-changing findings,” she said.

In the meantime, Hwang said, the study adds evidence that this population has a low risk for invasive disease and can rethink the typical leap to treatment triggered by hearing the word “cancer.” “We’ve always treated DCIS as a cancer, but I think these preliminary results at least start the conversation of thinking about DCIS and casting it in a very different way for both patients and clinicians who are taking care of them,” she said.

Thomas Celona is an editor at Cancer Today.