ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Transcriptomic Insights into Lobular Breast Cancer Biology and Patient Outcomes: Analysis of the MINDACT Clinical Trial.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeInvasive 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 (ER)-positive/HER2-negative ILC and ER+/HER2- IBC-NST; classic and nonclassic ER+/HER2- ILC; and recurring and nonrecurring ER+/HER2- ILC in patients with a low genomic risk and either a low clinical/low genomic (cL/gL) or high clinical/low genomic (cH/gL) risk. EXPERIMENTAL
designWe analyzed 4,262 ER+/HER2- tumors (63.7%; 464 ILC and 3,798 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 survival and distant recurrence-free survival.
resultsAn increased expression of CDH1 (E-cadherin) in IBC-NST compared with ILC was observed. ILC showed more uptake of extracellular lipid sources (LPL, CD36, LEP, and LEPR), whereas IBC-NST favored lipid synthesis (FASN). Decreased ER signaling, increased PI3K/Akt signaling, and differences related to the extracellular matrix were also observed in ILC. Classic and nonclassic ILC differed subtly, notably in cell-cycle regulation. In patients with ER+/HER2- ILC with a cL/gL risk, enrichment of apoptosis, inflammatory response, hypoxia, and oncogenic signaling (PI3K/Akt, Ras, and c-Myc) were associated with worse survival. In contrast, in the cH/gL group, associations between ILC transcriptomic features and survival were more subtle.
conclusionsThis represents the largest transcriptomic dataset for ILC from a clinical trial with central histology review. These findings may provide insights to refine treatment strategies and relapse risk assessment for patients with ILC.
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