Abstract

Simple SummaryBreast cancer remains the most frequent women cancer worldwide. The current policy of care for this cancer tends rather at therapeutic de-escalation, with therapies that evolve toward more targeted and more personalized treatments. Personalized medicine requires clinical, but also molecular characterization of tumors, and allows notably chemotherapy to be replaced, or at least used in combination with newer and more appropriate drugs. The aims of this study were (i) to describe recent tools (such as gene-expression signatures) aiding at decision-making in breast cancer management, and (ii) to focus on recent molecules that can be used either in association with chemotherapeutic drugs or after chemotherapies. Such molecules are of utmost importance to help avoid unnecessary chemotherapies. When substitution treatments are available (in early breast cancer for instance), a big step can be made toward personalized medicine for the patient’s benefit. This clinical strategy is a medical challenge for the upcoming years.In 2018, about 2.1 million women have been diagnosed with breast cancer worldwide. Treatments include—among others—surgery, chemotherapy, radiotherapy, or endocrine therapy. The current policy of care tends rather at therapeutic de-escalation, and systemic treatment such as chemotherapies alone are not systematically considered as the best option anymore. With recent advances in the understanding of cancer biology, and as a complement to anatomic staging, some biological factors (assessed notably via gene-expression signatures) are taken into account to evaluate the benefit of a chemotherapy regimen. The first aim of this review will be to summarize when chemotherapies can be avoided or used only combined with other treatments. The second aim will focus on molecules that can be used instead of chemotherapeutic drugs or used in combination with chemotherapeutic drugs to improve treatment outcomes. These therapeutic molecules have emerged from the collaboration between fundamental and clinical research, and include molecules, such as tyrosine kinase inhibitors, CDK4/6 inhibitors, and monoclonal antibodies (such as anti-PD-L1). In the fight against cancer, new tools aiding decision making are of the utmost importance: gene-expression signatures have proven to be valuable in the clinic, notably, to know when chemotherapies can be avoided. When substitution treatments are also available, a big step can be made toward personalized medicine for the patient’s benefit.

Highlights

  • IntroductionTreatments include surgery, chemotherapy, radiotherapy, or endocrine therapy, among others

  • As the first woman-related cancer in the US [1] and worldwide [2], breast cancer (BC)remains a complex public health issue

  • Efficiency of chemotherapy has been proved for decades for patients with BC in both neo-adjuvant and adjuvant regimens, and radiotherapy, endocrine and anti-HER2 therapies are largely used with success, the only important thing to consider is that patients still die from BC

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Summary

Introduction

Treatments include surgery, chemotherapy, radiotherapy, or endocrine therapy, among others. The current policy of care tends at therapeutic de-escalation and toward more personalized treatments (depending, among others, on histological classifications, Scarff–Bloom–Richardson (SBR) grade, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression, and Ki67 index). Despite these adjusted treatments, local or distant recurrence inexorably still occurs, leading patients to die [3]. Chemotherapies are not always the best option, as their induced toxicities remain a major concern. At the dawn of the 2020s, new tools are available for decision making

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