What are the different types of breast cancer and their presentations?

Types of Breast Cancer and Their Clinical Presentations

Breast cancer is a heterogeneous disease with distinct molecular subtypes that have different clinical presentations, prognoses, and treatment approaches. Understanding these subtypes is crucial for appropriate management and optimizing patient outcomes.

Molecular Classification of Breast Cancer

The molecular classification divides breast cancer into four main subtypes:

1. Luminal A

   • Characteristics: ER+/PR+, HER2-, low Ki-67
   • Presentation: Often presents as smaller tumors with lower grade
   • Prognosis: Best prognosis among all subtypes (92-97% 5-year overall survival) 1
   • Metastatic pattern: Primarily spreads to bone 1
   • Local recurrence rate: 3.7% 1

2. Luminal B

   • Characteristics: ER+/PR+, HER2+ or HER2- with high Ki-67
   • Presentation: More aggressive than Luminal A
   • Prognosis: Good but worse than Luminal A (88-91% 5-year overall survival) 1
   • Metastatic pattern: Similar to Luminal A but more aggressive

3. HER2-enriched

   • Characteristics: ER-/PR-, HER2+
   • Presentation: Often higher grade, more aggressive
   • Prognosis: Intermediate (82-85% 5-year overall survival) 1
   • Metastatic pattern: Preferentially spreads to liver and lung 1
   • Local recurrence rate: 7.5% 1
   • Distant metastasis rate: 25.6% 1

4. Triple-negative/Basal-like

   • Characteristics: ER-/PR-/HER2-
   • Presentation: Higher grade, more aggressive features
   • Prognosis: Poorest among subtypes (77-83% 5-year overall survival) 1
   • Metastatic pattern: Higher propensity for brain and liver metastases 1
   • Demographics: More common in younger women (<40 years), African American women, and BRCA1 mutation carriers 2, 1
   • Recurrence pattern: Higher risk within first 3 years after diagnosis 1

Histological Classification

Breast cancer can be divided into:

1. Non-invasive carcinomas

   • Ductal Carcinoma In Situ (DCIS): Confined to ducts, no invasion through basement membrane 2
   • Lobular Carcinoma In Situ (LCIS): Confined to lobules, considered a risk factor rather than true cancer 2

2. Invasive carcinomas

   • Invasive Ductal Carcinoma (IDC): Most common type (~75% of cases) 3
   • Invasive Lobular Carcinoma (ILC): Second most common, often presents with larger tumors and more advanced stage at diagnosis compared to IDC 4
   • Special histological types (accounting for ~25% of invasive breast cancers) 3, 5:
     • Mucinous carcinoma: Less aggressive, better prognosis, less likely to present at advanced stage 4
     • Tubular carcinoma: Excellent prognosis, less likely to present at advanced stage 4
     • Medullary carcinoma: Despite basal-like features, may have better prognosis than other triple-negative cancers 3, 4
     • Inflammatory breast cancer: Aggressive presentation with skin changes (peau d'orange), often advanced stage at diagnosis 2, 4
     • Papillary carcinoma: Usually lower grade, better prognosis 4
     • Adenoid cystic carcinoma: Despite basal-like features, has favorable prognosis 3
     • Metaplastic carcinoma: Aggressive subtype with heterogeneous presentation 3

Clinical Presentation

Breast cancer presentation varies by subtype but may include:

1. Palpable mass: Most common presentation
2. Skin changes:
   • Dimpling
   • Peau d'orange (orange peel appearance) - common in inflammatory breast cancer
   • Ulceration - seen in advanced cases
3. Nipple changes:
   • Discharge
   • Retraction
   • Paget's disease (crusting, scaling, erythema of nipple) 2
4. Axillary lymphadenopathy: More common in aggressive subtypes
5. Asymptomatic: Detected on screening mammography

TNM Staging

The TNM staging system categorizes breast cancer based on:

1. Tumor size (T):

   • Tis: Carcinoma in situ
   • T1: ≤20 mm
   • T2: >20 mm but ≤50 mm
   • T3: >50 mm
   • T4: Any size with extension to chest wall or skin 2

2. Nodal involvement (N):

   • N0: No regional lymph node metastases
   • N1-N3: Increasing levels of nodal involvement 2

3. Metastasis (M):

   • M0: No distant metastasis
   • M1: Distant metastasis

Triple-Negative Breast Cancer (TNBC)

TNBC deserves special attention due to its aggressive nature:

• Represents 10-20% of all breast cancers 2, 1
• Higher prevalence in:
  • Premenopausal women
  • Women of African descent (threefold increased risk) 2
  • BRCA1 mutation carriers 1
• Further classified into subtypes:
  • Basal-like (BL1 and BL2) - ~75% of TNBC cases
  • Mesenchymal (M) and mesenchymal stem-like (MSL)
  • Immunomodulatory (IM)
  • Luminal androgen receptor (LAR) 1
• Characterized by:
  • High mitotic index
  • High nuclear pleomorphism
  • High histological grade 1
  • Early recurrence pattern (within first 3 years) 1

Clinical Implications

Understanding breast cancer subtypes is critical for:

1. Prognosis: Molecular subtypes provide more accurate prognostic information than histological type alone
2. Treatment selection: Different subtypes respond to different therapeutic approaches
3. Follow-up planning: More intensive follow-up needed for aggressive subtypes, especially in first 3 years for TNBC 1

Pitfalls to Avoid

1. Relying solely on histological type: Some histological special types with good prognosis (medullary, adenoid cystic) may display poor-prognosis basal-like transcriptomes 3
2. Overlooking molecular testing: Essential for all invasive breast cancers to determine ER, PR, and HER2 status 2
3. Assuming all triple-negative cancers have poor prognosis: Some special histological types with triple-negative profile may have better outcomes 3
4. Delaying treatment for aggressive subtypes: Particularly important for triple-negative and HER2+ disease

Understanding the complex interplay between histological and molecular subtypes is essential for optimal breast cancer management and improving patient outcomes.