Combined endocrine and targeted therapy in luminal breast cancer

ABSTRACT

Introduction: For decades, endocrine therapy has been the cornerstone of management for luminal breast cancer. Despite the substantial benefit derived by patients from endocrine therapy, primary and secondary resistances to endocrine therapy are serious clinical issues.

Areas covered: Today, in the advanced setting, three distinct classes of targeted agents mTOR, CDK 4/6, and PI3K inhibitors, are approved for use. CDK 4/6 inhibitors have improved outcomes substantially, changing the natural history of advanced luminal breast cancer. Current studies seek to bring CDK 4/6 inhibitors to the early setting. This review will cover all available data on target therapy combinations with endocrine therapy for both the early and advanced settings, including approved drugs and agents in development.

Expert opinion: Combined endocrine and target therapy has changed the landscape in advanced disease. In early disease, it is possible to have a large impact, particularly in patients with higher risk of relapse. Trials like ADAPTCYCLE seek to leverage neoadjuvant data to de-escalate treatment, substituting chemotherapy for CDK 4/6 inhibitors. In advanced diseases, studies such as PADA-1 point toward a future in which ctDNA will be used to define management before clinical progression occurs.

KEYWORDS:

• Abemacicilib
• alpelisib
• estrogen receptor
• luminal breast cancer
• palbociclib
• ribociclib

Article highlights

• Luminal breast cancer is the most common subtype of breast cancer.

• Endocrine therapy is the cornerstone of management in luminal breast cancer in both early and advanced diseases.

• Endocrine resistance, however, remains an important clinical issue.

• Pathways involved in the biology of endocrine resistance have been well studied in the last two decades, leading to the development of several classes of targeted agents which have been approved.

• CDK 4/6 inhibitors are the most important of these, having changed the natural history of this disease in the advanced setting and are currently being studied in the early setting.

Declaration of interest

M Goldner has received travel grants from United Medical. N Pondé has received lecture fees from Novartis, Lilly, Roche and AstraZeneca, and has received advisory board fees from Lilly. S Sanches has received lecture fees from Pfizer, AstraZeneca, Lilly, Novartis, and Amgen. S Sanches has also received travel grants from United Medica and Novartis, and advisory board fees from Pfizer, AstraZeneca, Lilly, MSD and Novartis. J Lima has received lecture fees and has served on the advisory boards from Lilly and Novartis. N Pandolfi has received a travel grant from MSD.

The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper received no funding.