Clinical Scorecard: Molecular Features and Progress in Targeted Therapies for HR-Positive, HER2-Low Breast Cancer

At a Glance

Key Highlights

• HR-positive HER2-low breast cancer accounts for nearly 60% of breast cancer cases.
• Diagnosis involves immunohistochemistry and fluorescence in situ hybridization.
• Endocrine therapy is the cornerstone of treatment, with CDK4/6 inhibitors as standard for advanced cases.
• Antibody-drug conjugates like deruxtecan have improved patient prognosis.
• The classification of HER2 status is evolving to include HER2-low expression.

Guideline-Based Recommendations

Diagnosis

• Use immunohistochemistry and fluorescence in situ hybridization for HER2 status assessment.
• HER2-low is defined as IHC 1+ or IHC 2+ with negative FISH.

Management

• Endocrine therapy is the primary treatment approach.
• Consider CDK4/6 inhibitors for advanced first-line treatment.

Monitoring & Follow-up

• Utilize digital pathology, next-generation sequencing, and circulating tumor DNA for dynamic monitoring.

Risks

• Patients may experience primary or acquired endocrine resistance.

Patient & Prescribing Data

Patients with HR-positive, HER2-low breast cancer.

Combination therapies and novel anti-HER2 agents are crucial for treatment.

Clinical Best Practices

• Integrate endocrine therapy with targeted anti-HER2 strategies.
• Report HER2-low status explicitly in pathology reports.

Related Resources & Content

• DESTINY-Breast 04 trial
• ASCO and CAP HER2 testing guidelines