Abstract GS5-05: Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance)

Abstract

Background: Standard treatment for ductal carcinoma in situ (DCIS) consists of surgery, often followed by adjuvant radiation therapy or endocrine therapy. This current approach is thought to represent overtreatment for some patients. This study was undertaken to determine whether an alternate approach of primary endocrine therapy alone could result in measurable radiographic changes in unresected estrogen receptor (ER)-positive DCIS. Methods: A phase II open-label single arm multi-center cooperative group trial (CALGB 40903) was conducted for postmenopausal patients diagnosed with ER-positive DCIS. All eligible patients underwent baseline mammography and MRI, followed by 6 months of preoperative therapy with letrozole. Follow up breast MRI was obtained at 3 and 6 months of treatment. The primary endpoint was change in total MRI volume of DCIS enhancement from baseline to 3 months and from baseline to 6 months. Secondary endpoints were change in MRI maximum diameter over baseline and change in mammographic extent of disease over baseline. Endpoints were analyzed via 2-sided paired t-tests (a=0.05). Results: From 8/1/12 to 2/1/16 108 patients were enrolled; Of the 77 patients who completed letrozole treatment per protocol, 66 patients were assessable. 2 additional patients who did not complete treatment per protocol were considered assessable and thus included in the analysis for a total of 68 patients. Median age of the cohort was 62.7 years. DCIS nuclear grade was low in 10% of patients, intermediate in 49%, and high in 40%. 82% of patients had ER-positive, PR-positive DCIS. The total mean MRI volume decreased from baseline to 3 months by 1.93 cm3 (p<0.001) and from baseline to 6 months by 1.82 cm3 (p<0.001). There was no significant difference in tumor volume between 3 and 6 months. Mean total mammographic tumor diameter decreased from baseline to 6 months by 3.31 mm2 (p=0.078). Conclusions: In a cohort of postmenopausal women treated with 6 months of preoperative endocrine therapy for ER-positive DCIS, MRI volume decreased markedly by 3 months, while mammographic extent of disease was not altered significantly. Correlation of imaging changes with pathology and baseline biomarkers will be conducted. These results will help determine whether MRI could be an effective modality for monitoring treatment response in some patients treated with primary endocrine therapy for ER-positive DCIS. Citation Format: Hwang ES, Duong S, Bedrosian I, Allred J, Wisner D, Hyslop T, Caudle A, Guenther J, Hudis C, Winer E, Esserman L, Hylton N. Primary endocrine therapy for ER-positive ductal carcinoma in situ (DCIS) CALGB 40903 (Alliance) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-05.

De-Escalation of Locoregional Therapy in Low-Risk Disease for DCIS and Early-Stage Invasive Cancer

“…More notably, however, there was a 15% rate of pathologic complete response (pCR), including a 75% rate of pCR among patients with low-grade disease. 46 Such data support a more individualized approach for DCIS, which could be based on projected risk of invasive progression rather than merely the diagnosis of DCIS.…”

Ductal carcinoma in situ: current and future management for the surgeon and non-surgeon: a narrative review

“…A phase II clinical trial studied the MRI volume detected changes in post-menopausal DCIS patients who are ER positive and receiving 6 months of neoadjuvant daily oral letrozole (55). There was a 33% decrease in DCIS volume detected on MRI after 3 months of letrozole, which did not increase after 6 months of therapy.…”

Update Breast Cancer 2018 (Part 1) – Primary Breast Cancer and Biomarkers

“…But such data are not available for patients with ductal carcinoma in situ (DCIS), although the question of whether patients with DCIS should receive anti-hormone therapy and if so, which patients with DCIS should receive it, is currently being discussed. A recent single-arm phase-II trial (CALGB 40903) investigated outcomes after a 6-month therapy with letrozole in a preoperative setting in 55 patients with estrogen receptor-positive (≥ 1% positive cells in immunohistochemistry) DCIS 24 . The aim of the study was to identify those subgroups who would benefit most from systemic anti-hormone therapy.…”

“…Für Patientinnen mit einem duktalen Carcinoma in situ (DCIS) sind solche Daten jedoch nicht bekannt, obwohl es eine Diskussion gibt, ob und welche DCIS-Patientinnen mit einer antihormonellen Therapie behandelt werden sollten. Eine kürzliche, einarmige Phase-II-Studie (CALGB 40903) hat eine 6-monatige Therapie mit Letrozol im präoperativen Setting bei 55 Patientinnen mit östrogenrezeptorpositivem (≥ 1% positive Zellen in der Immunhistochemie) DCIS untersucht 24 . Ziel der Studie war die Identifikation von Subgruppen, die am ehesten für eine systemische antihormonelle Therapie geeignet sind.…”