Refining Breast Tumor Classification Could Lead to Improved Clinical Trials

Cancer researchers have suggested changing the way breast tumors are classified after finding that the basal-like or triple-negative class of tumors is actually biologically heterogeneous.

Triple-negative (TN) and basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormone receptors and overexpression and/or amplification of HER2 (human epidermal growth factor receptor 2).

Considering that up to 30% of tumors identified as triple-negative do not actually fall into the basal-like subtype category, investigators at the University of North Carolina (Chapel Hill, USA) and their colleagues at the Vall d’Hebron Institute of Oncology (Barcelona, Spain) analyzed more than 1,700 tumor samples from 12 publicly available datasets in order to fine-tune the class definitions.

They reported in the February 12, 2013, online edition of the journal the Oncologist results of molecular characterizations, which compared and contrasted the results in terms of common patterns and distinct patterns for each class of tumor. In total, when testing 412 TN and 473 BL tumors, 21.4% and 31.5% were identified as non-BL and non-TN, respectively. TN tumors identified as luminal or HER2-enriched (HER2E) showed undistinguishable overall gene expression profiles when compared versus luminal or HER2E tumors that were not TN. Similar findings were observed within BL tumors regardless of their TN status, which suggested that molecular subtype was preserved regardless of individual marker results. Interestingly, most TN tumors identified as HER2E showed low HER2 expression and lacked HER2 amplification, despite the similar overall gene expression profiles to HER2E tumors that were clinically HER2-positive.

“Our findings have very important implications for clinical trials focused on triple-negative breast cancers,” said senior author Dr. Charles Perou, associate professor of genetics at the University of North Carolina. “Future clinical trials focused on triple-negative breast cancers should consider stratifying patients based on basal-like versus non-basal-like gene expression profiles, which appear to be the main biological difference seen in patients with triple-negative breast cancer. In addition, our findings argue for very rigorous hormone receptor and HER2 testing due to the known reproducibility issues associated with these pathology-based biomarkers. Recognizing the molecular diversity of triple-negative tumors and subclassifying them as separate entities could support efforts to identify new biomarkers, which might possibly result in tests for subtype specific responses to different treatments, and conduct more targeted research on the clinical importance of the various molecular subtypes.”

Related Links:
University of North Carolina
Vall d’Hebron Institute of Oncology