Mixed Cancer Types (MIXED)

Overview

The MIXED OncoTree code designates tumors with mixed histologic features that do not cleanly fit a single cancer type. In the breast cancer context within this corpus, it specifically denotes mixed invasive ductal/invasive lobular carcinoma (mixed IDC/ILC), which accounts for approximately 3–11% of invasive breast cancers. These tumors contain elements of both ductal and lobular morphology and have historically been classified as a distinct entity, but molecular profiling indicates they are not a third hybrid class.

Cohorts in the corpus

  • brca_tcga_pub2015 — 88 mixed IDC/ILC tumors profiled alongside 127 ILC and 490 IDC samples; the largest molecular characterization of this histologic category to date PMID:26451490.

Recurrent alterations

  • Mixed IDC/ILC tumors molecularly resolve into ILC-like (24/88) or IDC-like (64/88) classes by majority vote of three orthogonal classifiers (ISOpure, OncoSign-adapted, ElasticNet); CDH1 mutation status is the dominant discriminating feature — all CDH1-mutated mixed tumors classified as ILC-like PMID:26451490.
  • CDH1 alteration rate in mixed tumors is intermediate between ILC (63%) and IDC (2%), consistent with the histologic mixture PMID:26451490.
  • MET500 cohort (n=500 metastatic solid tumors across 20 cancer types) is the defining MIXED-lineage study in this corpus: top three types were PRAD (18.6%), BRCA (18.2%), and SARCNOS (8.4%); pan-cancer somatic landscape across lineages found TP53 (53.2%), CDKN2A (16%), PTEN (15.8%), PIK3CA (13.4%), AR (12.6%), and KRAS (10.2%) as most-altered genes. PMID:28783718

Subtypes

  • Mixed IDC/ILC tumors are not a third molecular entity; they are best characterized as ILC-like or IDC-like based on CDH1 status and multi-platform molecular profiles PMID:26451490.
  • The clinical designation “mixed ductal/lobular” aggregates tumors with “IDC with lobular features” — a non-standardized pathology criterion that contributes to molecular heterogeneity in this category PMID:26451490.

Therapeutic landscape

  • Treatment implications for mixed IDC/ILC depend on the molecular ILC-like vs IDC-like classification: ILC-like mixed tumors inherit the high pAKT/AKT pathway activation typical of ILC, suggesting potential benefit from PI3K/AKT/mTOR inhibition; IDC-like mixed tumors follow IDC biology PMID:26451490.
  • Metastatic surveillance for ILC-like mixed tumors should include anatomical (CT) rather than PET scanning, given low metabolic activity characteristic of ILC PMID:26451490.

Sources

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