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Progress in adjuvant systemic therapy for breast cancer

Nature Reviews Clinical Oncology volume 16, pages 27–44 (2019)Cite this article

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Abstract

The prognosis of patients with early stage breast cancer has greatly improved in the past three decades. Following the first adjuvant endocrine therapy and chemotherapy trials, continuous improvements of clinical outcomes have been achieved through intense therapeutic escalation, albeit with increased health-care costs and treatment-related toxicities. In contrast to the advances achieved in surgery or radiotherapy, the identification of the patient subgroups that will derive clinical benefit from therapeutic escalation has proved to be a daunting process hindered by a lack of collaboration between scientific groups and by the pace of drug development. In the past few decades, initiatives towards de-escalation of systemic adjuvant treatment have achieved success. Herein, we summarize attempts to escalate and de-escalate adjuvant systemic treatment for patients with breast cancer and argue that new, creative trial designs focused on patients’ actual needs rather than on maximizing drug market size are needed. Ultimately, the adoption of effective treatments that do not needlessly expose patients and health-care systems to harm demands extensive international collaboration between academic groups, governments, and pharmaceutical companies.

Key points

  • The use of adjuvant systemic therapy has improved the outcomes of patients with early stage breast cancer over the past four decades.

  • Incremental improvements in outcomes have been obtained through systematic escalation of treatment standards, a process that has also increased treatment-associated toxicities and costs.

  • Important examples of escalation approaches in the past few years include those for dose-dense therapy and post-neoadjuvant capecitabine for patients with triple-negative disease, extended endocrine therapy for patients with oestrogen receptor-positive disease, and dual blockade for patients with HER2+ disease.

  • Despite extensive efforts in translational and biomarker research, limited achievements have been obtained beyond those derived from the gene signature panels currently available, which can be used to spare a subset of patients from chemotherapy.

  • Some efforts towards treatment de-escalation approaches have been successful, notably, the regimen combining paclitaxel and trastuzumab and non-anthracycline regimens.

  • Sustainable progress necessitates a change in trial design, strong international collaborations, and integration of research on predictive biomarkers into the design of registration trials.

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Fig. 1: West German Study Group ADAPT trial80 model.
Fig. 2: POETIC trial75 model.
Fig. 3: I-SPY 2 trial148 model.
Fig. 4: Trial model involving circulating tumour DNA integration.

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Authors and Affiliations

  1. Research Department, Institut Jules Bordet, Academic Promoting Team, Brussels, Belgium

    Noam F. Pondé

  2. Breast International Group, Brussels, Belgium

    Dimitrios Zardavas

  3. Research Department, Institut Jules Bordet, Brussels, Belgium

    Martine Piccart

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  1. Noam F. Pondé
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  3. Martine Piccart
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All authors contributed to researching data for the article, discussions of content, writing the manuscript, and editing and reviewing the manuscript before publication.

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Correspondence to Martine Piccart.

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Competing interests

N.F.P. has received speaker honoraria from Mundipharma. D.Z. works at the Breast International Group, which has received grants from Genentech, Novartis, Pfizer, Puma Biotechnology, Roche, and Tesaro. M.P. has received consultant honoraria from AstraZeneca, Crescendo Biologics, Debiopharm, Huya, Lilly, MSD, Novartis, Odonate, Periphagen, Pfizer, PharmaMar, and Roche/Genentech and is a board member of Radius. She works at Jules Bordet Institute, which has received research grants from AstraZeneca, Lilly, MSD, Novartis, Pfizer, Roche/Genentech, Radius, Servier, and Synthon.

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Pondé, N.F., Zardavas, D. & Piccart, M. Progress in adjuvant systemic therapy for breast cancer. Nat Rev Clin Oncol 16, 27–44 (2019). https://doi.org/10.1038/s41571-018-0089-9

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