Letrozole Presurgery Yields Drastic Biomarker Changes in ER+ DCIS
Presurgery letrozole led to significant imaging and biomarker changes in postmenopausal patients with estrogen receptor (ER)-positive ductal carcinoma in situ (DCIS) in a phase 2 clinical trial (J Clin Oncol. 2020;38[12]:1284-1292).
“Primary endocrine therapy for [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 [ER-positive] DCIS,” explained lead investigator E. Shelley Hwang, MD, MPH, Duke Cancer Institute, Duke University, Durham, North Carolina, and colleagues.
A total of 79 postmenopausal patients diagnosed with ER-positive DCIS without invasion were enrolled in the multi-center, single-arm study and given letrozole 2.5 mg daily for 6 months before surgery.
Dr Hwang and co-investigators collected breast magnetic resonance imaging (MRI) data at baseline, 3 months, and 6 months, and assessed for a primary end point of change in 6-month MRI enhancement volume versus baseline.
Ultimately, 70 patients completed 6 months of letrozole therapy, 67 of whom had MRI data available for each timepoint. Findings showed baseline MRI volumes ranging from 0.004 to 26.3 cm3, and median reductions from baseline (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).
According to the investigators, there were consistent reductions 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).
Among 59 patients who had surgery per study protocol, 50 (85%) had persistent DCIS, 6 (10%) had invasive disease, and 9 (15%) had no residual DCIS or invasive disease.
“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,” Dr Hwang et al concluded.—Hina Porcelli
