Abstract
PATIENTS AND METHODS
We analyzed 4261 ER+/HER2- tumors (63.7%, 464 ILC, 3798 IBC-NST) with central pathology review. Differential gene expression analysis was adjusted for age and grade, followed by gene set enrichment analysis. Adjusted regression models evaluated associations of transcriptomic profiles with disease-free (DFS) and distant recurrence-free survival (DRFS).
CONCLUSIONS
This represents the largest transcriptomic dataset for ILC from a clinical trial with central histology review. Findings may provide insights to refine treatment and relapse risk assessment for ILC patients.
RESULTS
An increased expression of CDH1 (E-cadherin) in IBC-NST compared to ILC was observed. ILC showed more uptake of extracellular lipid sources (LPL, CD36, LEP, LEPR), while IBC-NST favored lipid synthesis (FASN). Decreased ER-signaling, increased PI3K/Akt-signaling, and differences related to the extracellular matrix was also observed in ILC. Classic and non-classic ILC differed subtly, notably in cell cycle regulation. In ER+/HER2- ILC patients with a cL/gL risk, enrichment of apoptosis, inflammatory response, hypoxia and oncogenic signaling (PI3K/Akt, Ras, c-Myc) was associated with worse survival. In contrast, in the cH/gL group, associations between ILC transcriptomic features and survival were more subtle.
BACKGROUND
Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer after invasive breast cancer of no special type (IBC-NST). This retrospective analysis of the MINDACT trial investigated transcriptomic differences between estrogen receptor-positive/HER2-negative (ER+/HER2-) ILC versus ER+/HER2- IBC-NST, classic and non-classic ER+/HER2- ILC, and, recurring and non-recurring ER+/HER2- ILC in patients with a low genomic risk and either a low (cL/gL) or high clinical risk (cH/gL).