What are the different types of breast cancer?

Types of Breast Cancer

Breast cancer is classified into five distinct molecular subtypes based on hormone receptor and HER2 status: Luminal A (ER/PR positive, HER2 negative, low Ki-67), Luminal B (ER/PR positive with HER2 positive or high Ki-67), HER2-positive (ER/PR negative, HER2 amplified), Triple-Negative/Basal-like (ER/PR/HER2 negative), and Normal Breast-like tumors. 1, 2

Primary Molecular Classification System

The modern classification framework divides breast cancer into subtypes with distinct biological behaviors and treatment implications:

Luminal A Subtype (Most Common, Best Prognosis)

• Defined by: ER positive and/or PR positive (strongly positive), HER2 negative, low Ki-67 proliferation index (<20%), and low histologic grade (typically grade I or II) 2, 3
• Clinical significance: Represents the most common and least aggressive molecular subtype with the best prognosis among all breast cancer subtypes 3
• Treatment approach: Endocrine therapy alone is sufficient for the majority of cases; chemotherapy reserved only for high tumor burden or grade 3 tumors 3
• Metastatic pattern: Predominantly metastasizes to bone 2

Luminal B Subtype (Intermediate Prognosis)

• Defined by: ER positive and/or PR positive, with either HER2 positive status OR high Ki-67 (>20%) OR low PR expression 1, 3
• Key distinction from Luminal A: Higher proliferation rate (Ki-67 >20%) or low progesterone receptor expression differentiates this from Luminal A 3
• Clinical behavior: More aggressive than Luminal A, often high grade despite hormone receptor positivity 1

HER2-Positive Subtype

• Defined by: ER negative, PR negative, with HER2 gene amplification and high expression 1
• Molecular characteristics: Shows distinct gene expression patterns with amplification of the HER2 gene 2
• Treatment implications: Requires HER2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy 4
• Metastatic pattern: Preferentially metastasizes to liver and lung 2
• Prognosis: Approximately 5-year median overall survival in metastatic setting 4

Triple-Negative Breast Cancer (TNBC) / Basal-like Subtype (Poorest Prognosis)

• Defined by: ER negative, PR negative, HER2 negative; basal-like tumors additionally express cytokeratin 5/6 and/or EGFR 1, 5
• Critical distinction: Approximately 75% of TNBC cases are basal-like, but 25% are not; these terms are NOT interchangeable 1, 5
• Prevalence: Accounts for 10-20% of invasive breast cancers 1
• High-risk populations: Three times more common in women of African descent and pre-menopausal women 1
• Aggressive features: Higher mitotic index (OR = 11.0), more marked nuclear pleomorphism (OR = 9.7), higher combined grade (OR = 8.3), and more TP53 mutations (44% vs 15% in Luminal A) 1, 5
• Prognosis: Peak recurrence risk within 3 years, increased mortality for 5 years post-diagnosis; 5-year survival for late-stage disease only 14% in African-American women 1, 5
• Metastatic pattern: Preferentially metastasizes to liver and brain 2
• Treatment: Chemotherapy alone (no targeted therapy available for classic TNBC) 4
• Survival in metastatic setting: Approximately 1-year median overall survival 4

Normal Breast-like Subtype

• Defined by: Distinct gene expression profile resembling normal breast tissue 1
• Clinical relevance: Less well-characterized subtype with uncertain clinical significance 1

Key Clinical Considerations

Pathological Assessment Requirements

• Essential markers: ER, PR, HER2 status (by IHC or FISH/CISH), Ki-67 proliferation index, and histologic grade must be assessed 1, 2
• Quality control: Ki-67 interpretation must be standardized with local laboratory values and quality assurance programs 3
• Timing: Can be assessed on core biopsy before treatment or on definitive surgical specimen if neoadjuvant therapy not planned 1

Staging Considerations

• TNM staging: Remains important for all subtypes but must be interpreted in context of molecular subtype 2
• Lymph node status: Significantly impacts prognosis across all subtypes 2

Common Pitfalls to Avoid

• Do not conflate triple-negative with basal-like: While overlapping, these are distinct entities requiring different classification approaches 1, 5
• Do not rely on surrogate markers alone: Accurate subtype classification requires meticulous quality control and standardized assessment 3
• Do not ignore Ki-67 in Luminal tumors: The Ki-67 cutoff of 20% is critical for distinguishing Luminal A from Luminal B and has major treatment implications 2, 3

Prevalence by Subtype

• Hormone receptor positive/HER2 negative (Luminal A/B): 70% of patients 4
• HER2-positive: 15-20% of patients 4
• Triple-negative: 15% of patients 4