Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2018 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Molecular, biologic and clinical profiling of chromosomal instable, hormone receptor positive, invasive ductal breast cancer (IDBC).
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr e12524)
Author(s): David Demanse, D. Pinet, S. Bailey, H. Bitter, W. Hackl; Novartis Pharma AG, Basel, Switzerland
Background: The relationship between sporadic breast cancer and the accumulation of molecular abnormalities resulting from estrogens and other carcinogens is well established. The spectrum of molecular changes is diverse, including numerical or structural chromosomal abnormalities, gene expression alterations and epigenetic changes. The objective of this study was to determine the molecular profile of the subpopulation of ER and/or PR positive, HER2 negative IDBCs of the METABRIC collection (N = 1.104) characterized by high chromosomal instability (25%). Methods: Clinical-pathologic and genomic variables (oncogenic mutations/CNVs, gene expression) were used to develop a parsimonious prognostic model for disease free survival using a robust, innovative statistics approach combined with cross-validation methodology. The predictive accuracy of the different sets of information was assessed using time-dependent ROC curves. Results: Common molecular features of this IDBC subpopulation include RB deficiency, TP53 loss-of-function mutation (41%), 11q13-14 (30%) and/or 8p11-12 (25%) amplification and PIK3CA gain-of-function mutation (32%). Hallmarks include high proliferation activity, defect apoptosis, epithelial-mesenchymal- transformation (EMT), BRCA-ness, multiple-drug resistance (MDR) and early relapse. Classification based on clinical-pathologic baseline variables revealed a subgroup of tumors with low (35%) and another one with high distant recurrence risk at 5 years (65%). The estimated relapse-free-survival rate at 5 years of the whole group of chromosomal instable, ER and/or PR positive, HER2 negative IDBCs was statistically significantly shorter compared to chromosomal stable luminal IDBCs (77% [95%CI: 72; 82] vs 91% [89; 93]) and comparable to the group of triple negative IDBCs of the METABRIC collection (70% [95%CI: 65; 76]). Conclusions: Collectively our data suggest that chromosomal instable, luminal IDBCs represent a novel and unique entity of luminal breast cancers of very high medical need. Implications for the molecular diagnosis of this entity of luminal breast cancers and their treatment will be discussed.
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