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🩺 Breast Cancer Pathology — MUHS Exam Notes

(Source: Johari Pathology, Pages 301–312)

1. ANATOMY OF BREAST (Female Breast)

Two major components:

Terminal Duct-Lobular Unit (TDLU) — Most important! This is where most breast carcinomas arise.
Large Duct System (LDS)

TDLU structure:

Lobule + intralobular & extralobular terminal ducts
Each lobule = terminal ductules/acini + specialized intralobular stroma
Ducts → subsegmental → segmental → lactiferous duct → nipple
Lactiferous sinus = fusiform dilation beneath nipple (between collecting & segmental duct)

2. CARCINOMA OF BREAST — KEY FACTS

2nd most common cancer in females (1st = carcinoma of cervix)
Almost all breast carcinomas = adenocarcinomas
Develops usually after age of 25; incidence peaks at 70–80 years

3. ETIOLOGY / RISK FACTORS (Important for MCQs & Short Notes)

Category	Risk Factors
Endogenous	Early menarche, Late menopause, Late age at first pregnancy, Nulliparity, Obesity, Atypical hyperplasia
Exogenous	HRT (hormone replacement therapy), Oral contraceptives, High-fat diet, Alcohol
Environmental	Radiation, Toxins, Cigarette smoking
Genetic	BRCA1/BRCA2 mutations, Family history (1st-degree relatives)
Protective factors	Breastfeeding ✅, Exercise ✅, Healthy body weight ✅, Coffee/caffeine (may reduce risk)

Important BRCA points:

~5–10% breast cancers = germline mutations in tumor suppressor genes
BRCA2 mutations → ER-positive cancers (HER2-negative, high proliferation)
BRCA1 mutations → Triple negative (ER−, HER2−) cancers
BRCA1/2 mutations occur at different frequencies in different ethnic groups

4. HISTOLOGICAL CLASSIFICATION (Write this in exams!)

A. Precursor Lesions / Noninvasive Carcinoma:

Ductal Carcinoma In Situ (DCIS) — 23%
Lobular Carcinoma In Situ (LCIS) — 6%

B. Invasive (Infiltrating) Breast Carcinoma:

Invasive carcinoma of No Special Type (NST) — most common — 9%
Invasive lobular carcinoma
Special histologic types:
- Medullary carcinoma
- Mucinous (colloid) carcinoma
- Tubular carcinoma

C. Papillary Lesions: Intraductal papilloma, Intraductal papillary carcinoma, Solid papillary carcinoma

D. Tumors of Nipple: Nipple adenoma, Paget disease of nipple

E. Fibroepithelial Tumors: Fibroadenoma, Phyllodes tumor (low/high grade)

F. Clinical Pattern: Inflammatory carcinoma

5. DUCTAL CARCINOMA IN SITU (DCIS)

Malignant cells limited to ducts/lobules by basement membrane
Myoepithelial cells are preserved ← key differentiating feature
Involves small and medium-sized ducts; can spread to entire breast sector

DCIS Subtypes:

Subtype	Key Feature
Comedo (High-grade)	Solid sheets of large, pleomorphic cells + central necrosis with dystrophic calcification
Solid DCIS	Tumor cells completely fill the involved spaces
Cribriform DCIS	Evenly distributed, regular "cookie-cutter-like" spaces between cells
Papillary DCIS	Papillae with fibrovascular cores; no myoepithelial layer
Micropapillary DCIS	Bulbous protrusions without fibrovascular core

Prognosis:

If untreated, small low-grade DCIS may develop into invasive cancer
Mastectomy for DCIS = curative in >95% of patients

6. MOLECULAR CLASSIFICATION (Important Table — Learn for Long Questions)

Type	ER+/HER2− (Luminal)	HER2+	Triple Negative (ER−/HER2−)
%	Low prolif: 40–55% / High prolif: 10%	~20%	~15%
Patient type	Older women, men	Young women, BRCA2 carriers	Young women, BRCA1 carriers
Metastasis	Bone (70%), visceral (25%), brain (<10%)	Bone (80%), visceral (30%), brain (10%)	Bone (40%), visceral (35%), brain (25%)
Chemo response	<10%	15–30%	~30%
Recurrence	Late (>10 years)	Intermediate	Short (<5 years)

7. MORPHOLOGY OF INVASIVE DUCTAL CARCINOMA (Short Note Question)

Gross:

Firm to hard in consistency
Irregular outline/border
On cut section → characteristic grating sound (like cutting a water chestnut)
Cut surface retracts below the surface

Microscopy (Graded by Nottingham Histologic Score / Scarff-Bloom-Richardson):

Graded on 3 parameters:

Tubule formation
Nuclear pleomorphism
Mitotic rate

Grade	Features
Grade I (Well-differentiated)	Prominent tubules, small round nuclei, rare mitoses
Grade II (Moderately differentiated)	Some tubules + solid clusters/single cells, more pleomorphism, mitotic figures present
Grade III (Poorly differentiated)	Solid sheets, high pleomorphism, numerous mitoses

8. SPREAD OF BREAST CARCINOMA

Local spread: Skin (nipple, areola), Chest wall

Lymphatic spread:

Axillary lymph nodes (most important!)
Internal mammary lymph nodes
Supraclavicular lymph nodes

Distant (Hematogenous) spread:

Lung, Liver, Brain, Bone (most common site)

9. PROGNOSTIC FACTORS (Important for Long Answer)

A. Extent-Related Factors:

In situ vs Invasive — Most DCIS are cured; ~50% of invasive have metastases at diagnosis
Distant metastases — Cure unlikely
Axillary lymph node status — MOST IMPORTANT prognostic factor (in absence of distant mets)
- Sentinel node = first draining node
- Macrometastasis = >0.2 cm; Micrometastasis = ≤0.2 cm
Tumor size — Larger tumor → greater risk of nodal metastasis
Locally advanced disease — Skin/muscle invasion = bad prognosis
Inflammatory carcinoma:
- Breast erythema + skin thickening
- Peau d'orange (orange peel appearance) due to Cooper ligament tethering
- Caused by dermal lymphatic blockage by metastatic carcinoma
- Poor prognosis; >60% ER-negative, 40–50% overexpress HER2
Lymphovascular invasion — Present in ~50% of invasive carcinomas; poor prognosis

B. Biology-Related Factors:

Molecular subtype (determined by IHC for ER, HER2, proliferation)
Special histologic type — Tubular, mucinous, medullary, lobular, papillary → better survival
Histologic grade (Nottingham score) — Grades 1–3; strongly correlated with survival
Proliferative rate (Ki-67, cyclins) — High proliferation = worse prognosis but may respond better to chemo
ER/PR status:
- ER+ PR+ → respond to hormonal therapy; less likely to respond to chemotherapy
- ER− PR− → respond to chemotherapy
HER2/neu overexpression → Poorer survival; but responds to targeted therapy (trastuzumab)

10. TRIPLE ASSESSMENT IN BREAST CANCER

Clinical examination
Radiological examination (mammography)
FNAC (Fine Needle Aspiration Cytology)

11. FIBROADENOMA (Short Note Question)

Most common benign tumor of female breast
Derived from intralobular stroma
Age: 20–30 years
Clinically: Palpable, freely movable mass = "Breast mouse"

Gross:

Single or multiple; unilateral or bilateral
Well-circumscribed, rubbery, glistening, grayish-white
Contains slit-like spaces; size = 1–4 cm

Microscopy: Mixture of duct-like structures + fibrous connective tissue

Type	Key Feature
Pericanalicular	Round/oval glands with patent lumen; stroma proliferates circumferentially around ducts
Intracanalicular	Connective tissue invaginates into glands; ducts compressed into curvilinear slits

✅ High-Yield One-Liners for MUHS

Fact	Answer
Most common benign tumor of breast	Fibroadenoma
Most important prognostic factor in breast cancer	Axillary lymph node status
Cancer with peau d'orange	Inflammatory carcinoma
Breast cancer in situ with preserved myoepithelial cells	DCIS
Grading system for invasive breast carcinoma	Nottingham (Scarff-Bloom-Richardson)
Triple negative breast cancer associated with	BRCA1 mutation
HER2+ cancer associated with	BRCA2 mutation
Most common site of distant metastasis	Bone
Mastectomy cure rate in DCIS	>95%
Triple assessment components	Clinical + Mammography + FNAC

Only highlight the main topic not the subtopic write only heading of topics

Breast Cancer Pathology — Main Topics

Anatomy of Female Breast
Carcinoma of Breast — Key Facts
Etiology / Risk Factors
Histological Classification
Ductal Carcinoma In Situ (DCIS)
Molecular Classification
Morphology of Invasive Ductal Carcinoma
Spread of Breast Carcinoma
Prognostic Factors
Triple Assessment in Breast Cancer
Fibroadenoma

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