Imaging features of genomic instability in circulating tumor cells (CTCs) from metastatic triple-negative breast cancer (metTNBC) patients (pts) who received PIKTOR

Autor: Priscilla Ontiveros, Joyce O'Shaughnessy, Beverly Hom, Ryan Dittamore, Yipeng Wang, Maren K Levin
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Oncology. 37:e14527-e14527
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2019.37.15_suppl.e14527
Popis: e14527 Background: A subset of TNBCs have homologous recombination deficiency (HRD) with upregulation of compensatory DNA repair pathways. A combination of TAK-228 and TAK-117 (PIKTOR), investigational oral TORC1/2 and PI3Kα selective inhibitors, respectively, is hypothesized to increase genomic instability (GI) and decrease double strand DNA repair. CTCs from metTNBC pts are being characterized for imaging features that may correlate GI in blood obtained at baseline (BL) prior to beginning PIKTOR, and at disease progression (PD) on PIKTOR. Pts are treated with a cisplatin-based regimen after PD on PIKTOR. Methods: Following IRB-approved informed consent, metTNBC pts received 4 mg PO TAK-228 and 200 mg PO TAK-117 QDx3d QW until PD. Blood samples collected at BL and at PD were sent to Epic Sciences for CTC analyses including enumeration, cell morphology, phenotypic heterogeneity, and GI analysis via a previously developed GI prediction algorithm based on cell phenotypes (Jendrisak et al AACR 2018). Results: The 9 pts treated with PIKTOR to date had mets in lymph nodes (n = 8), lung (n = 5), chest wall (n = 2), and bone (n = 2). Median number of prior regimens for metTNBC was 2; median duration of PIKTOR treatment was 8 wks (range, 5-15). CTCs were detected in 62.5% (5/8) BL and 100% (9/9) PD samples. 2 pts had high phenotypic CTC heterogeneity at both BL and PD (pt#36: 0.69 to 0.64; pt#80: 0.93 to 1.41), 1 pt had increased heterogeneity (pt#75: 0 to 1.68) and 1 pt had decreased heterogeneity (pt#67: 1.26 to 0) post-PIKTOR. 1 pt had predicted phenotypic GI (pGI+) CTCs detected at both BL and PD (pt#80), 1 pt had pGI+ CTCs at BL only (pt#36) and 1 pt at PD only (pt#75). Higher expression of the epithelial marker, cytokeratin (CK), and larger cell size were observed in the PD samples. Conclusions: Following treatment with and PD on PIKTOR, higher CK expression, higher phenotypic heterogeneity, and more pGI+ CTCs were observed in a subset of pts, suggesting that these TN CTCs may have developed epithelial transition and greater GI with PIKTOR treatment. Accrual continues and CTC GI biomarkers will be correlated with pts’ response to subsequent cisplatin-based therapy.
Databáze: OpenAIRE
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