Abstract
Inflammatory breast cancer (IBC) is a rare, aggressive cancer found in all the molecular breast cancer subtypes. Despite extensive previous efforts to screen for transcriptional differences between IBC and non-IBC patients, a robust IBC-specific molecular signature has been elusive. We report a novel IBC-specific gene signature (59 genes; G59) that achieves 100% accuracy in discovery and validation samples (45/45 correct classification) and remarkably only misclassified one sample (60/61 correct classification) in an independent dataset. G59 is independent of ER/HER2 status, molecular subtypes and is specific to untreated IBC samples, with most of the genes being enriched for plasma membrane cellular component proteins, interleukin (IL), and chemokine signaling pathways. Our finding suggests the existence of an IBC-specific molecular signature, paving the way for the identification and validation of targetable genomic drivers of IBC.
Highlights
Inflammatory breast cancer (IBC) is a rare form of breast cancer associated with poor prognosis compared to other subtypes, and this is attributed to its therapy resistance and a high metastatic potential [1,2,3]
To control for any variability in signature discovery caused by the molecular breast cancer subtypes, we matched both Estrogen receptor (ER) and Human epidermal growth factor receptor 2 (HER2) status of 22/24 samples used for training (Fig. 1a, left, see highlighted ER and HER2 scores)
G59 is the first IBC signature to be successfully validated in an independent dataset and shows the highest accuracy (100% (45/45) in GSE45581 and (60/61) 98.4% in GSE111477) in its prediction [9]
Summary
IBC is a rare form of breast cancer associated with poor prognosis compared to other subtypes, and this is attributed to its therapy resistance and a high metastatic potential [1,2,3]. The majority of IBC patients present with late-stage disease wherein the cancer has spread beyond the primary site [4]. To better diagnose and treat IBC patients, the IBC research community is working on defining an IBC-specific molecular signature. The largest study was published through the establishment of the World IBC Consortium which identified 79 genes, molecular subtype-independent, IBC signature [5]. After, another 132 genes, subtype-independent, IBC signature was reported [6]. Another 132 genes, subtype-independent, IBC signature was reported [6] Both signatures were seen in ~ 16.4% and ~ 25% of breast cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
