A newly released study examining adjuvant therapy in patients with ductal carcinoma in situ (DCIS) following breast-conserving surgery confirms previous findings on the role of radiation and demonstrates when endocrine therapy may benefit patients, using a seven-gene predictive DCIS biosignature.

“Past studies such as NSABP B24 and NSABP B35 have looked at the role of endocrine therapy in DCIS and have shown a benefit,” says Chirag Shah, MD, a physician in Cleveland Clinic’s Department of Radiation Oncology, Co-director of the Breast Cancer Program and second author on the study. “However, we wanted to ascertain if all patients derive a consistent benefit and if some do not require endocrine therapy given that endocrine therapy is associated with side effects and additional costs.”

Study methods and analysis

Patients with DCIS have traditionally been treated with breast-conserving surgery, followed by radiotherapy and adjuvant endocrine therapy based on multiple randomized and prospective clinical trials. However, those trials have failed to identify subsets of patients who do not benefit from adjuvant radiation therapy or endocrine therapy after breast-conserving surgery.

The multi-center study, which was presented at the annual meeting of the American Society of Clinical Oncology in June, evaluated the ability of a seven-gene predictive DCIS biosignature to assess the impact of endocrine therapy on 10-year ipsilateral breast recurrence risk after breast-conserving surgery alone or with radiation therapy.

“We looked at the three groups that the biosignature defines – low risk, elevated risk and residual risk – and evaluated the impact of adjuvant endocrine therapy for each, as well as the interaction of radiation and endocrine therapy,” says Dr. Shah. The three groups are defined by decision scores (DS) from the DCISionRT® test with integrated residual risk subtype (RRt) by PreludeDX: Low risk (DS ≤ 2.8), elevated risk (DS > 2.8 without RRt) and residual risk (DS > 2.8 with RRt). The groups were assessed for 10-year total ipsilateral breast recurrence risk by Kaplan Meier and Cox proportional hazards survival analysis.

Results and clinical implications

The study included approximately 900 women who were treated with breast conserving surgery with or without adjuvant radiation therapy and with or without endocrine therapy. Results were as follows:

• For low-risk patients, there was no benefit to endocrine therapy in patients treated with breast-conserving surgery without radiation therapy. Also, no benefit was seen with radiation therapy after breast-conserving surgery. This was consistent with previous studies evaluating the biosignature.
• For patients in the elevated risk group, there was a benefit to the addition of radiation, but no additional benefit to endocrine therapy for those who received radiation. However, there was a benefit to endocrine therapy for patients who did not receive radiation.
• In the residual risk group, there was no benefit to endocrine therapy for patients who received radiation; while radiation reduced rates of recurrence, rates of recurrence in this cohort remained elevated compared to other groups. Among patients not receiving radiation, endocrine therapy reduced recurrence rates.

Dr. Shah says the results point to the need for conversations and informed decision-making with patients in all three groups.

“It spurs the discussion with low-risk patients about whether surgery alone is adequate given their low risk of recurrence,” he says. “For elevated-risk patients, perhaps a short course of radiation should be considered as a substitute for endocrine therapy. Similarly, do we need to adjust or intensify our treatment strategy in patients with residual risk, given that they are still at an elevated risk regardless of what we do?”

Dr. Shah and his colleagues would like to conduct follow-up research, tracking the study participants for 10 years to determine long-term outcomes in patients with breast-conserving surgery with or without radiation therapy and/or endocrine therapy.