Abstract CT086: Treatment of ductal carcinoma in situ (DCIS) with pasireotide, an IGF-I inhibitor

Abstract

Abstract DCIS is a non-obligate precursor in which epithelial cells with features of cancer reside in and expand otherwise normal appearing mammary ducts and lobules. DCIS increases the relative risk of developing invasive breast cancer (IBC) by up to 10 fold. Treatment of DCIS includes breast conserving surgery (BCS), tumor margins permitting, followed by radiation, or mastectomy. Recently we found that pasireotide, a somatostatin analog inhibitor of IGF-I, was effective in reducing cell proliferation and increasing apoptosis in patients with atypical hyperplasia (AH) and or proliferative disease of the breast. At present there are no recognized medical treatments for DCIS. Here we raise the possibility that pasireotide might also be an effective therapy for some DCIS. To make this determination, 8 patients previously diagnosed with DCIS were treated with pasireotide, 600µg twice daily subcutaneously for a period of 20 days. Lesion size was assessed on DCE-MRIs in 3 planes before and after treatment. Of the eight, two had lesions characterized as low grade DCIS on core biopsy, 4 had intermediate or intermediate to high grade lesions, and two had high grade lesions. After treatment they all had surgical excision biopsies. We also measured proliferation and apoptosis to assess effects of pasireotide by expression of Ki67 and caspase 3. To confirm that the effect of pasireotide was mediated via the IGF-I pathway, p-AKT and p-ERK 1/2 were evaluated. Core and excision samples from 14 untreated patients where used as control. Overall, treatment with pasireotide reduced DCIS lesion size by ≥30% according the RECIST criteria in 4 of 8 patients, as measured by DCE-MRI. Of those, pathology of the surgical excision confirmed that there was no remaining DCIS tissue in the two patients with low grade disease. The two additional lesions that were reduced in size one was intermediate to high grade and the other a high grade DCIS. The remaining 4 patients had tumors that were stable in size. Pasireotide reduced cell proliferation and significantly increased apoptosis in the DCIS lesions. While DCIS is less responsive to pasireotide than AH and proliferative disease, it may nevertheless provide a window of opportunity for treatment and possibly eradication of some low grade or higher grade DCIS as well. The main side effect included hyperglycemia, intestinal discomfort and rash or redness at the injection area. Our data show that hyperglycemia disappears relatively fast after ending treatment with pasireotide. In conclusion, treatment with pasireotide eliminated 2 low grade DCIS lesions, shrunk two higher grade ones and also decreased proliferation and increased apoptosis. Additional evidence in a larger number of patients will be necessary. Citation Format: Irineu Illa-Bochaca, Linda Moy, Julia Smith, Debora Axelrod, Baljit Singh, David L. Kleinberg. Treatment of ductal carcinoma in situ (DCIS) with pasireotide, an IGF-I inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT086. doi:10.1158/1538-7445.AM2017-CT086