Gynecology Topic 42. Breast cancer

I. Definition, Epidemiology, Risk Factors

Definition and Epidemiology

• Breast cancer: Malignant tumor derived mostly from epithelial cells of breast ducts or lobules.
• Most common cancer in women excluding skin cancer; second most common cause of cancer-related death in women.
• Male breast cancer is rare, about 0.5-1% of breast cancers.

Risk Factors

• Age: Risk increases with age.
• Family history and genetic predisposition: Especially BRCA1/BRCA2 mutation; consider genetic counseling in young, bilateral, triple-negative, male, or strong family-history cases.
• Hormonal factors: Early menarche, late menopause, nulliparity/late first pregnancy, hormone replacement therapy.
• Previous breast cancer or high-risk proliferative lesion.
• Radiation exposure, especially chest irradiation at young age.
• Lifestyle: Obesity, alcohol, smoking, physical inactivity.

II. Pathology and Tumor Biology

Histologic Types

1. Invasive ductal carcinoma / no special type: ~70-80%; cords/nests of malignant ductal epithelial cells; often hard irregular mass.
2. Invasive lobular carcinoma: ~10-15%; single-file pattern; more often multifocal/bilateral.
3. Other types: Mixed, mucinous/colloid, tubular, papillary, medullary.

In Situ Disease and Receptors

• Carcinoma in situ: Malignant epithelial proliferation without basement membrane invasion.
• DCIS: Often detected on mammography by microcalcifications.
• LCIS: Often incidental; marker of increased future invasive breast cancer risk.
• Required tumor tests: ER, PR and HER2 because they guide endocrine and targeted therapy.
• Hormone receptor-positive → endocrine therapy useful; HER2-positive → anti-HER2 therapy useful; triple-negative → chemotherapy-based treatment.

III. Clinical Features, Screening, Diagnosis

Clinical Features

• Often asymptomatic and detected by screening mammography.
• Painless breast lump: Hard, irregular, fixed, usually non-tender.
• Nipple changes: Retraction, inversion, bloody/clear spontaneous discharge.
• Skin changes: Dimpling, tethering, thickening, erythema, ulceration, peau d'orange.
• Axillary/supraclavicular lump → lymph node involvement.
• Metastatic signs: Bone pain, dyspnea/cough, liver symptoms, neurologic symptoms, weight loss.

Screening

• Mammography is the main screening test; detects masses, architectural distortion and microcalcifications.
• Population screening age/interval varies by country; many European programs use mammography every 2 years in middle-aged/older women.
• High-risk patients, especially BRCA carriers, need individualized earlier MRI + mammography screening.

Triple Diagnosis of a Breast Abnormality

1. History + clinical breast examination:

• Inspection: Asymmetry, skin changes, scars, visible masses, nipple changes.
• Palpation: Start with normal/asymptomatic breast; assess size, mobility, borders, consistency, location and nodes.
• Upper outer quadrant is a common cancer site because most breast tissue is there.

2. Imaging:

• Diagnostic mammography ± ultrasound; suspicious findings include irregular/spiculated mass and clustered pleomorphic microcalcifications.
• MRI: Selected use for high-risk screening, extent assessment or occult/problem-solving cases.

3. Biopsy:

• Core needle biopsy: Preferred for histology, grade and ER/PR/HER2 receptor testing.
• FNAB: Cytology only; less information than core biopsy.
• Excisional biopsy: If percutaneous biopsy is not possible or results are discordant.

IV. Staging and Spread

TNM Staging

1. T0: No evidence of primary tumor; Tis: carcinoma in situ.
2. T1: Tumor <=2 cm.
3. T2: Tumor >2-5 cm.
4. T3: Tumor >5 cm.
5. T4: Direct extension to skin/chest wall or inflammatory carcinoma.

• N0: No regional lymph node metastasis.
• N1: Mobile ipsilateral axillary lymph node metastasis.
• N2: Fixed/matted axillary or clinically apparent internal mammary lymph node metastasis.
• N3: Supra-/infraclavicular nodes, extensive axillary nodes, or axillary + internal mammary involvement.
• M0: No distant metastasis; M1: distant metastasis.

Spread

• Local invasion: Skin, nipple, chest wall.
• Lymphatic spread: Axillary nodes → supraclavicular/infraclavicular/internal mammary nodes.
• Hematogenous spread: Bone, lung, liver, brain.

V. Treatment

General Principles

• Treatment depends on stage, operability, histology, ER/PR/HER2 status, menopausal status, comorbidity and patient preference.
• Local treatment: Surgery ± radiotherapy.
• Systemic treatment: Endocrine therapy, chemotherapy and targeted therapy according to receptor/risk profile.

Surgical Treatment

• Breast-conserving surgery / lumpectomy: Tumor excision with clear margins, usually followed by whole-breast radiotherapy; typical early-stage option.
• Mastectomy: Removal of breast tissue; simple/total mastectomy removes breast tissue only.
• Modified radical mastectomy: Breast removal + axillary lymph node dissection.
• Sentinel lymph node biopsy: Standard axillary staging for clinically node-negative invasive breast cancer.
• Axillary lymph node dissection: Clinically positive nodes or selected positive sentinel-node/bulky disease cases.

Radiotherapy

• After lumpectomy: Usually required to reduce local recurrence.
• After mastectomy: Used for high-risk features such as large tumor, positive margins, chest wall/skin involvement or significant nodal disease.

Systemic Therapy

• Endocrine therapy for ER/PR-positive cancer:

• Tamoxifen: SERM; breast anti-estrogen effect.
• Aromatase inhibitors: Anastrozole/letrozole/exemestane; mainly postmenopausal or with ovarian suppression.
• Raloxifene: Mainly prevention in high-risk postmenopausal women, not standard invasive-cancer treatment.

• Chemotherapy: Node-positive, large, high-grade, triple-negative, HER2-positive or otherwise high-risk tumors.
• Targeted therapy: Trastuzumab ± other HER2-directed drugs for HER2-positive breast cancer.
• Locally advanced disease: Often neoadjuvant systemic therapy → surgery → radiotherapy.
• Metastatic disease: Usually palliative systemic therapy with symptom-directed local treatment.