Metastatic HER2-low carcinoma of the breast is a newly recognized subset of breast cancer characterized by low HER2 expression. It represents a significant proportion of cases previously categorized as HER2-negative. Advances in treatment strategies have led to new targeted therapies, offering hope for improved patient outcomes.
Understanding HER2-Low Breast Cancer
HER2 (human epidermal growth factor receptor 2) is a protein that influences breast cancer growth. Traditionally, breast cancers were classified as HER2-positive or HER2-negative. However, HER2-low refers to tumors with a HER2 immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification.
Causes and Risk Factors
While the exact causes of HER2-low metastatic breast cancer are unclear, several factors contribute to its development:
- Genetic Mutations: BRCA1 and BRCA2 mutations may be involved.
- Hormone Receptor Status: Most HER2-low cancers are hormone receptor-positive (HR+), though triple-negative cases exist.
- Family History: A family history of breast cancer increases risk.
- Environmental and Lifestyle Factors: Smoking, alcohol use, and obesity may contribute.
Symptoms of Metastatic HER2-Low Breast Cancer
The symptoms of metastatic breast cancer depend on the organs affected:
- Bone Metastases: Bone pain, fractures, and weakness.
- Lung Metastases: Shortness of breath, persistent cough.
- Liver Metastases: Jaundice, abdominal pain, weight loss.
- Brain Metastases: Headaches, vision changes, seizures.
Diagnosis and Staging
1. Imaging Tests:
- Mammography and ultrasound detect primary tumors.
- MRI and PET scans assess metastatic spread.
2. Biopsy and Pathological Analysis:
- Immunohistochemistry (IHC) and in situ hybridization (ISH) determine HER2 status.
- Hormone receptor (HR) testing identifies treatment options.
3. Blood Tests:
- Tumor markers and circulating tumor DNA (ctDNA) may provide additional diagnostic insights.
Treatment Options
Treatment for metastatic HER2-low breast cancer involves a combination of systemic therapies:
1. Targeted Therapy
- Trastuzumab Deruxtecan (T-DXd): A promising antibody-drug conjugate for HER2-low tumors.
2. Endocrine Therapy (for HR-positive cases)
- Aromatase inhibitors (AI), selective estrogen receptor modulators (SERMs), and selective estrogen receptor degraders (SERDs).
3. Chemotherapy
- Used when hormonal or targeted therapies are ineffective.
4. Immunotherapy
- Pembrolizumab may be considered for PD-L1 positive cases.
5. Palliative Care and Supportive Treatments
- Radiation therapy for bone metastases and pain management strategies.
Prognosis and Survival Rates
Survival rates vary based on tumor biology, response to treatment, and metastatic spread. Emerging therapies have improved median overall survival (OS) for HER2-low patients.
Metastatic HER2-low breast cancer represents an evolving field with promising advancements. Personalized treatment approaches, including targeted therapies, offer hope for improved patient outcomes. Ongoing research continues to refine strategies to enhance survival and quality of life.
