Clinical implications of the intrinsic molecular subtypes of breast cancer.

Breast

Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Published: November 2015

AI Article Synopsis

  • Gene-expression profiling has identified 5 main subtypes of breast cancer, providing deeper insights into the disease's biology and potential treatment strategies.
  • Within hormone receptor-positive and HER2-negative cancers, Luminal A and B subtypes can predict long-term outcomes and recurrence risk, influencing treatment decisions.
  • In triple-negative breast cancer, the Basal-like subtype is predominant, and distinguishing it from non-Basal-like groups may help predict responses to various chemotherapy regimens.

Article Abstract

Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

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http://dx.doi.org/10.1016/j.breast.2015.07.008DOI Listing

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