What are the possible contributing factors in pathogenesis of carcinoma breast ? Describe briefly histopathology of different types of breast carcinoma.

Pathogenesis of Carcinoma Breast

The pathogenesis of breast carcinoma is multifactorial, involving interactions between genetic, hormonal, and environmental factors. These factors contribute to the initiation, promotion, and progression of the disease.

• Genetic Factors: Approximately 5-10% of breast cancers are linked to inherited gene mutations, most notably in BRCA1 and BRCA2 genes. Mutations in other genes like TP53, PTEN, and ATM also increase risk.
• Hormonal Factors: Prolonged exposure to estrogen is a significant risk factor. Early menarche, late menopause, nulliparity (never having given birth), and hormone replacement therapy (HRT) increase estrogen exposure.
• Reproductive History: Age at first full-term pregnancy (older age increases risk), number of pregnancies (more pregnancies generally decrease risk), and breastfeeding duration (longer duration decreases risk) all play a role.
• Lifestyle Factors: Obesity, lack of physical activity, alcohol consumption, and smoking are associated with increased risk.
• Environmental Factors: Exposure to ionizing radiation, particularly during adolescence, can increase risk.
• Inflammation: Chronic inflammation in the breast tissue can contribute to cancer development.

Histopathology of Different Types of Breast Carcinoma

1. Invasive Ductal Carcinoma (IDC) – No Special Type (NST)

This is the most common type (70-80% of cases). Histologically, it’s characterized by:

• Tumor cells infiltrating the breast ducts and surrounding stroma.
• Variable differentiation – from well-differentiated (resembling normal ducts) to poorly differentiated (lacking ductal features).
• Formation of nests, cords, or sheets of malignant cells.
• Desmoplastic reaction – dense, fibrous stroma surrounding the tumor cells.

2. Invasive Lobular Carcinoma (ILC)

Represents 10-15% of cases. Key histological features include:

• Tumor cells infiltrating the breast lobules and surrounding stroma in a single-file pattern (“Indian file” arrangement).
• Loss of E-cadherin expression, a cell adhesion molecule, contributing to the infiltrative pattern.
• Cells are often small, round, and lack prominent nucleoli.
• Often presents as a diffuse thickening rather than a distinct mass.

3. Inflammatory Breast Carcinoma (IBC)

A rare but aggressive form (1-5% of cases). Histological features include:

• Tumor cells blocking dermal lymphatic vessels, leading to skin edema and erythema (redness).
• Often lacks a palpable mass.
• Dermal lymphatic invasion by tumor cells is a hallmark feature.
• Frequently associated with poor prognosis.

4. Medullary Carcinoma

Represents approximately 3-5% of cases. Histological features include:

• Well-circumscribed, soft, and fleshy tumor.
• Large, atypical cells with prominent nucleoli and abundant cytoplasm.
• Heavy lymphocytic infiltrate surrounding the tumor cells.
• Often associated with a better prognosis compared to other invasive ductal carcinomas.

5. Mucinous Carcinoma

Represents approximately 1-2% of cases. Histological features include:

• Tumor cells floating in abundant extracellular mucin.
• Cells are typically well-differentiated.
• Often presents as a well-defined mass.
• Generally has a favorable prognosis.

Carcinoma Type	Key Histological Features	Frequency (%)
Invasive Ductal Carcinoma (NST)	Infiltration, variable differentiation, desmoplastic reaction	70-80
Invasive Lobular Carcinoma	“Indian file” pattern, E-cadherin loss	10-15
Inflammatory Breast Carcinoma	Dermal lymphatic invasion, skin edema	1-5
Medullary Carcinoma	Well-circumscribed, lymphocytic infiltrate	3-5