Neoadjuvant endocrine therapy in postmenopausal women with HR+/HER2- breast cancer

ABSTRACT

Introduction

While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women.

Areas covered

We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments.

Expert opinion

NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.

KEYWORDS:

• Breast cancer
• ER+
• HR+
• HR+/HER2-
• endocrine therapy
• neoadjuvant therapy
• Pre-operative therapy
• postmenopausal

Article highlights

• In postmenopausal women with HR+/HER2- breast cancer, NET is a safe and effective tool for disease downstaging, achieving higher breast conserving surgery rates than chemotherapy with lower toxicity.

• Aromatase inhibitors outperform tamoxifen and longer duration of NET might yield optimal effects.

• Baseline Ki67 is a prognostic factor and its level after a period of NET is an indicator of response, incorporated in numerous studies. However, Ki67 is not without its limitations as a surrogate marker of proliferation. Post-NET PEPI score holds prognostic value.

• Several genomic and hybrid signatures have been assessed for their value as predictors of NET response.

• The neoadjuvant setting offers unique research opportunities beyond monitoring of response, including studying the effect of early treatment and testing novel combination therapies.

• The COVID-19 pandemic led to increases in NET use, exhibiting the safety and efficacy of this strategy for downstaging and control of HR+/HER2- disease.

• Further validation and guidelines for biomarker use will be instrumental in helping standardize the use of NET, which remains underutilized in many territories despite the evidence for its safety and efficacy.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.