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  • Review Article
  • Published:

Challenges in the management of advanced, ER-positive, HER2-negative breast cancer

Nature Reviews Clinical Oncology volume 12, pages 541–552 (2015)Cite this article

Subjects

Key Points

  • In addition to phenotypic differences, recently discovered differences in genetic mutations between metastatic and early stage breast cancer mean the advanced state can be considered a different disease

  • New mutations in genes, such as ESR1, provide direct evidence of an evolving disease that likely confers treatment resistance and represent targets for future therapies

  • Other molecular adaptations that can occur in advanced disease also offer promising therapeutic targets using agents such as mTOR, CD4/6 and PI3K inhibitors

  • During metastasis, a switch to oestrogen receptor (ER) or HER2 positive disease is a recognized phenomenon, but the value of altering therapy on the basis of such changes is unclear

  • No biomarkers exist to guide endocrine or biological therapy choices in metastatic disease; however, an appreciation of the clinical evidence of resistance may help

  • Everolimus plus exemestane may be preferable after all lines of single agent endocrine therapy have been employed, and possibly following single-agent chemotherapy

Abstract

Hormone-receptor-positive breast cancer accounts for the majority—up to 80%—of all breast cancers. The evolution of breast cancer from early stage to the metastatic setting leads to increased heterogeneity, the occurrence of new mutations, and the development of treatment resistance representing a great challenge for management decisions. Unfortunately, little data exist to offer guidance in this context, and a reliance on traditional clinical parameters remains when deciding on optimal treatment. In advanced-stage oestrogen receptor-positive (ER+) disease, ongoing issues include the choice between endocrine therapy and chemotherapy, the appropriate sequence of treatment agents, and the incorporation of biological agents, such as everolimus, into the treatment armamentarium. In metastatic disease, repeated biopsies can help to reassess the receptor or genetic mutational status; however, the evidence to support this approach is limited. In this Review, we examine the current evidence that can guide treatment decisions in patients with advanced-stage ER+ breast cancer, discuss how to tackle these therapeutic challenges and provide suggestions for the optimal management of this patient population.

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Figure 1: Proposed treatment algorithms for postmenopausal patients with ER+ HER2–advanced-stage breast cancer suitable for endocrine therapy.

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Acknowledgements

We thank the Sandro Pitigliani Foundation for their generous support.

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Authors and Affiliations

  1. 'Sandro Pitigliani' Medical Oncology Unit, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, 59100, PO, Italy

    Christopher D. Hart, Laura Biganzoli & Angelo Di Leo

  2. Translational Research Laboratory, Hospital of Prato, Instituto Toscano Tumori, Via Suor Niccolina 20, Prato, 59100, PO, Italy

    Ilenia Migliaccio, Luca Malorni & Cristina Guarducci

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C.D.H. and I.M. researched data for article. C.D.H. and A.D.L. wrote the manuscript. C.D.H. and A.D.L. substantially contributed to discussion of content, and all authors reviewed and edited the manuscript before submission.

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Correspondence to Angelo Di Leo.

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L.M. is a consultant for AstraZeneca and has a research grant from Pfizer; A.D.L. receives honoraria from AstraZeneca and Novartis, and a research grant from Pfizer. The other authors declare no competing interests.

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Hart, C., Migliaccio, I., Malorni, L. et al. Challenges in the management of advanced, ER-positive, HER2-negative breast cancer. Nat Rev Clin Oncol 12, 541–552 (2015). https://doi.org/10.1038/nrclinonc.2015.99

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