Neo-adjuvant therapies for ER positive/HER2 negative breast cancers: from chemotherapy to hormonal therapy, CDK inhibitors, and beyond

ABSTRACT

Introduction

Chemotherapy has been traditionally used as neo-adjuvant therapy in breast cancer for down-staging of locally advanced disease in all sub-types. In the adjuvant setting, genomic assays have shown that a significant proportion of ER positive/HER2 negative patients do not derive benefit from the addition of chemotherapy to adjuvant endocrine therapy. An interest in hormonal treatments as neo-adjuvant therapies in ER positive/HER2 negative cancers has been borne by their documented success in the adjuvant setting. Moreover, cytotoxic chemotherapy is less effective in ER positive/HER2 negative disease compared with other breast cancer subtypes in obtaining pathologic complete responses.

Areas covered

Neo-adjuvant therapies for ER positive/HER2 negative breast cancers and associated biomarkers are reviewed, using a Medline survey. A focus of discussion is the prediction of patients that are unlikely to derive extra benefit from chemotherapy and have the highest probabilities of benefiting from hormonal and other targeted therapies.

Expert Opinion

Predictive biomarkers of response to neo-adjuvant chemotherapy and hormonal therapies are instrumental for selecting ER positive/HER2 negative breast cancer patients for each treatment. Chemotherapy remains the standard of care for many of those patients requiring neo-adjuvant treatment, but other neo-adjuvant therapies are increasingly used.

KEYWORDS:

• Neo-adjuvant
• pre-operative
• subtype
• luminal
• signal transduction
• estrogen receptor

Article highlights

• Neo-adjuvant systemic therapies are used in breast cancer for down-staging of locally advanced disease and for in vivo determination of drug sensitivity.

• In ER positive/HER2 negative breast cancers the benefit of adjuvant chemotherapy is variable and molecular assays have been validated to identify the many patients who are expected to derive minimal or no benefit. In the neo-adjuvant setting, chemotherapy is classically used in ER positive disease but its effectiveness is also variable.

• Both chemotherapy and hormonal therapies produce lower pathologic complete responses in ER positive/HER2 negative breast cancers compared with other breast cancer sub-types.

• Although neo-adjuvant chemotherapy is appropriate for some patients with ER positive/HER2 negative breast cancers, others derive minimal or no benefit and could be treated with hormonal therapies instead.

• New targeted therapies such as immune checkpoint inhibitors currently in trials, in combination with chemotherapy, improve outcomes in ER positive/HER2 negative breast cancers.

Declaration of interests

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 disclosrue

One reviewer: Research funding: Pfizer, Roche. Ad boards; Pfizer, Roche, Seagen, AZ. Speakers fees; Pfizer, Roche, Seagen, AZ, Gilead, Lily Esai. Conference support; Roche, Lily. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.