Phase II Single-Arm Study of Preoperative Letrozole for Estrogen Receptor–Positive Postmenopausal Ductal Carcinoma In Situ: CALGB 40903 (Alliance)

Abstract

PURPOSE Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)–positive DCIS. PATIENTS AND METHODS A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm3. Median reductions from baseline MRI volume (1.4 cm3) were 0.6 cm3 (61.0%) at 3 months ( P < .001) and 0.8 cm3 (71.7%) at 6 months ( P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.

Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium

“…High-risk lesions such as atypical hyperplasia and lobular carcinoma in situ express ER and are effectively treated with either tamoxifen or aromatase inhibitors [38,39]. ER + DCIS can be treated with preoperative endocrine therapy for 6 months (Priority C) [40]. For management of ER-disease see Surgical Oncology section.…”

Association Between Time to Operation and Pathologic Stage in Ductal Carcinoma in Situ and Early-Stage Hormone Receptor-Positive Breast Cancer

“…The association between pathologic upstaging and time to operation in DCIS patients has previously been studied in the NCDB, with results consistent with ours, although patients were not stratified by ER status. 2 The possible mitigating effect of NET on disease progression in ER+ DCIS has been demonstrated in a small series, 18 and was part of the recommended delay strategies during the pandemic. Although there were too few DCIS patients on NET to render an adequate analysis in the current study, taken together, these data suggest that initiation of NET in patients with ER+ DCIS is a reasonable delay strategy.…”

Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation

“…First, margin width, a crucial covariable used to support RT decisions, is not included in SEER data 10,11 . Similarly, SEER data does not include information on endocrine therapy 60,61 , though it is used as an adjuvant treatment after surgery with/without RT for DCIS [62][63][64] . We also observed that ER/PR-positive tumors treated with RT, had reduced risks of SHMs compared to counterparts with ER/PR-negative diseases.…”