What are the differences between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) in terms of characteristics, treatment approaches, and prognosis?

Differences Between Invasive Ductal Carcinoma and Invasive Lobular Carcinoma

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are distinct breast cancer entities with different clinical presentations, molecular profiles, treatment responses, and survival patterns that require recognition of their unique characteristics for optimal management.

Epidemiology and Frequency

• IDC represents 70-75% of all invasive breast cancers, making it the most common histologic subtype 1
• ILC accounts for 10-15% of invasive breast cancers, representing the second most common subtype 1, 2, 3

Clinical and Imaging Characteristics

Presentation Patterns

• ILC presents with larger tumor sizes at diagnosis compared to IDC 4, 5
• ILC more frequently presents at advanced stages (stage II: 35% vs 34%; stage III: 16% vs 11% for ILC vs IDC) 5
• ILC has a more subtle clinical and mammographic presentation, making detection more challenging than IDC 2, 3
• ILC demonstrates a diffuse, infiltrative growth pattern with small cells individually dispersed or arranged in linear cords, whereas IDC forms cohesive nests and tubules 6

Pathologic and Molecular Features

Histologic Characteristics

• IDC forms tubules and cohesive nests of cells, while ILC consists of small cells arranged in single-file linear cords or loose aggregates without tubule formation 6
• ILC is characterized by loss of E-cadherin expression, a key molecular distinction from IDC which retains E-cadherin 2, 3, 6

Hormone Receptor Status

• ILC has significantly higher rates of hormone receptor positivity: 96-97% ER-positive compared to 70-81% for IDC 6, 5
• ILC shows higher progesterone receptor positivity: 84% versus 57% for IDC 6
• Most ILCs are luminal A intrinsic subtype with favorable prognostic features 2

Tumor Grade and HER2 Status

• ILC more frequently presents with lower histologic grade compared to IDC 4, 6
• ILC has lower HER2 overexpression rates: 12% versus 23% for IDC 6
• ILC tumors are more likely to be well-differentiated 4

Nodal Involvement and Metastatic Patterns

• ILC demonstrates higher rates of lymph node metastases despite favorable tumor characteristics: 51% versus 34% for IDC 6
• ILC has distinct metastatic patterns with predilection for unusual sites including gastrointestinal tract, peritoneum, and retroperitoneum 2, 3

Survival Patterns: The Critical Time-Dependent Difference

Early Survival (0-5 Years)

• ILC shows superior survival in the first 5 years after diagnosis with excess mortality rate ratio (EMRR) of 0.64-0.71 compared to IDC 4, 5
• This early survival advantage persists despite higher nodal involvement and larger tumor size 4, 6

Late Survival (Beyond 5 Years)

• ILC demonstrates significantly worse survival after 5 years, with the pattern reversing between years 6-10 4, 5
• EMRR increases progressively in later years: 1.30 in years 6-10,1.49-1.75 in years 10-15, and 2.17 in years 16-20 4, 5
• This late recurrence pattern represents a critical clinical distinction, indicating need for extended surveillance and potentially prolonged endocrine therapy 5
• At 20 years, relative survival rates converge (0.72 for ILC vs 0.73 for IDC), but the temporal pattern differs markedly 4

Treatment Response Differences

Systemic Therapy

• ILC derives distinct benefit from systemic therapy compared to IDC, though the specific patterns differ 3
• Treatment decisions should be based on tumor histology, hormone receptor status, HER2 status, and stage, as outlined in standard guidelines 1
• Despite molecular differences, most clinical trials and guidelines treat breast cancer as a single entity, which may not be optimal for ILC 3

Surgical Considerations

• Both IDC and ILC are treated with either breast-conserving surgery plus radiation or mastectomy based on tumor characteristics, margin status, and patient factors 7, 8
• The same surgical principles apply: tumor ≤4 cm without gross multicentricity or diffuse malignant calcifications are indications for breast conservation 7

Critical Clinical Pitfalls

• Do not assume favorable prognosis based solely on hormone receptor positivity in ILC—the late recurrence pattern demands extended surveillance 4, 5
• Recognize that ILC's higher nodal involvement rate occurs despite lower grade and better receptor status, indicating more aggressive biological behavior than apparent 6
• Standard 5-year follow-up protocols are inadequate for ILC—surveillance must extend beyond 10-15 years given the late recurrence pattern 4, 5
• ILC requires dedicated clinical trials rather than extrapolating IDC data, given the distinct molecular profiles and treatment responses 2, 3

Pathologic Reporting Requirements

• All invasive carcinomas require documentation of: histologic type and grade, tumor size, lymph node status, margin status, ER/PR status, and HER2 status 1
• E-cadherin immunostaining can confirm ductal versus lobular origin when histologic features are ambiguous 6
• Standardized CAP protocols should be used for all breast specimen reporting to ensure complete documentation 1