Clinical implications of the non-luminal intrinsic subtypes in hormone receptor-positive breast cancer

Cancer Treatment Reviews
Juan M CejalvoAleix Prat

Abstract

Gene expression profiling has had a considerable impact on our understanding ofbreastcancer biology. Duringthelast decade, 4 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched [HER2-E] and Basal-like) have been identified and intensively studied. In this article, we review and discuss the clinical implications of the 2 non-luminal subtypes (i.e. HER2-E and Basal-like) identified within hormone receptor (HR)-positive disease. After reviewing 32 studies for a total of 13,091 samples, ∼8% and ∼ 15% of early and metastatic HR+/HER2-negative breast cancer, respectively, were found to be non-luminal. Clinically, HR+/HER2-negative/non-luminal subtypes have been associated with estrogen independence, chemo-sensitivity, resistance to CDK4/6 inhibition and poor outcome. Interestingly, EGFR/HER2 tyrosine kinase inhibition might be of value in the HR+/HER2-negative/HER2-E subtype. Finally, the HER2-E subtype within HR+/HER2 + disease represents ∼ 30% and has been associated with anti-HER2 sensitivity, chemo-sensitivity and resistance to CDK4/6 inhibition. In the upcoming years, retrospective and prospective clinical trials evaluating both biomarkers should lead to improvements in patient outcomes.

Citations

Jan 22, 2020·Nature Communications·Fara Brasó-MaristanyAleix Prat
Nov 19, 2019·Frontiers in Oncology·Ana Godoy-OrtizEmilio Alba
Sep 15, 2020·Current Opinion in Oncology·Sonia Pernas, Sara M Tolaney
Aug 28, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Valentina GuarneriPierfranco Conte
Sep 18, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eva CiruelosAleix Prat
Sep 24, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aleix PratJoel S Parker
Apr 8, 2020·Seminars in Cancer Biology·Emad A Rakha, Fresia G Pareja
Nov 6, 2020·The Lancet Oncology·Montserrat Muñoz, Aleix Prat
Mar 5, 2021·European Journal of Clinical Investigation·Elisa AgostinettoEvandro de Azambuja
May 19, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Lin WangJia Chen
Feb 27, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tomás PascualAleix Prat
May 30, 2021·Molecular Oncology·Fara Brasó-MaristanyAleix Prat
Aug 1, 2021·Breast Cancer Research and Treatment·Sonya ReidTuya Pal

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