DURHAM, NC – Breast cancers that are typically classified as triple-negative are in fact biologically heterogeneous and should be further classified into distinct molecular subtypes, according to a comprehensive study of breast cancer datasets. The study, published in the February issue of The Oncologist, was conducted by a team of scientists from the University of North Carolina at Chapel Hill and the Vall d’Hebron Institute of Oncology in Barcelona, Spain.
Previous research had identified four main subtypes of breast cancer: luminal A, luminal B, HER2-enriched and basal-like. Basal-like cancer has become more commonly known as triple-negative breast cancer to define breast cancers that lack expression of hormone receptors and overexpression and/or amplification of HER2 – even though up to 30 percent of tumors identified as triple-negative do not actually fall into the basal-like subtype category.
The study examined more than 1,700 samples from 12 publicly available datasets, and highlighted the following findings:
• Triple-negative and basal-like definitions should not be considered synonymous because considerable discordance exists.
• Triple-negative disease is a heterogeneous clinical entity composed of all the intrinsic molecular subtypes, with the basal-like tumors being the most frequent (70%).
• Triple-negative tumors that are identified as non-basal-like (such as HER2-enriched or luminal A/B) show nearly undistinguishable global gene expression patterns versus non-triple-negative tumors that are HER2-enriched or luminal A/B.
• Basal-like tumors that are non-triple-negative show similar genomic features, and an association with young age at diagnosis, as do basal-like tumors that are triple-negative.
• Previously described triple-negative heterogeneity in part reflects known intrinsic subtype biology and microenvironmental heterogeneity.
“Our findings have very important implications for clinical trials focused on triple-negative breast cancers,” said corresponding author Dr. Charles Perou, Ph.D., of the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill. “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.”
Perou and his colleagues suggest that 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.
“The last decade has seen an increasing emphasis on subtyping of common cancers such as breast cancer. Multiple assays have been devised that help oncologists determine prognosis of particular subsets. However, as we move into routine clinical use of these assays, the current study reminds us that there is more work to do in this complex field especially if we are to use molecular assays to help change therapy and predict outcomes,” said Shelley Earp, M.D., Director of the UNC Lineberger Comprehensive Cancer Center.
The full article titled “Molecular Characterization of Basal-Like and Non-Basal-Like Triple-Negative Breast Cancers” can be accessed at www.TheOncologist.com or contact: Sharon Lee at sharonlee@alphamedpress.com.
About The Oncologist
Established by oncologists to help physicians better manage their practices in an ever-changing environment, The Oncologist® is the official journal of the Society for Translational Oncology (STO). Now in its 18th year, this internationally peer-reviewed journal focuses on clear and concise interpretation addressing the multimodality diagnosis, treatment, and quality of life of the cancer patient. Each issue is meant to impact the practice of oncology and to facilitate significant communication in the introduction of new medical treatments and technologies. For more information, visit www.TheOncologist.com.
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