Breast cancer is an abnormal, uncontrolled proliferation of cells within breast tissue. It is the second leading cause of cancer death among women, after lung cancer, accounting for about 6% of all female deaths.

Diagnosis of Breast Cancer: Triple Assessment

1. Clinical Evaluation
   • Detection of lump(s) and regional lymph nodes through physical exam.
2. Imaging
   • Ultrasound for women <35 years.
   • Mammography for women >35 years.
3. Cytology or Histology
   • Fine needle aspiration (FNA), core biopsy, or open biopsy for pathological confirmation.

Clinical Manifestations

Presenting Complaints

• Painless breast lump in over 70% of cases.
• Painful breast lumps may occur due to:
  • Ischemic changes and necrosis
  • Inflammatory carcinoma
  • Lymphedema
  • Local invasion of muscles/nerves
  • Superimposed infection
  • Rapid tumor growth
• Nipple discharge , often unilateral and possibly bloody.
• Skin changes : ulceration, irritation, eczema, nipple inversion, peau d’orange (orange peel appearance).
• Rare metastatic symptoms without palpable mass : back pain, hemoptysis, cough.

Advanced Disease Symptoms

• Chronic cough (lung metastasis)
• Weight loss, anorexia, fatigue
• Upper limb swelling (lymphedema from axillary node involvement)
• Back pain (bone metastasis)
• Jaundice (liver involvement)

Risk Factors and Predisposing History

• Prior breast cancer (contralateral breast)
• Benign breast diseases with hyperplasia or atypia
• Age >50 years (peak incidence 35-45 years)
• Family history of breast, ovarian, or gastrointestinal cancers
• Nulliparity or late first pregnancy (>30 years)
• Early menarche (<13 years), late menopause (>50 years)
• Use of oral contraceptives or hormone replacement therapy
• Lack or short duration of breastfeeding
• Chest irradiation
• Obesity, smoking, alcohol consumption
• High-fat diet

Physical Examination

General

• Assess overall condition, wasting, dehydration, anemia
• Check for lymphadenopathy

Breast Examination

• Explain procedure and obtain consent
• Inspect breasts for:
  • Size and symmetry
  • Nipple changes (inversion, discharge)
  • Visible masses or skin changes (ulcers, peau d’orange)
• Palpate breasts in quadrants + axillary tail + peri-areolar area:
  • Note size, shape, margins, mobility, tenderness, consistency, skin changes
• Examine nipple discharge if present
• Examine regional lymph nodes: axillary, supraclavicular, infraclavicular

Findings Suggestive of Malignancy

• Fixation to skin or chest wall
• Irregular, firm mass with irregular borders
• Skin dimpling, nipple inversion, peau d’orange
• Enlarged, hard, fixed lymph nodes
• Unilateral bloody nipple discharge with associated mass

Differential Diagnosis

• Giant fibroadenoma
• Fibrosarcoma
• Deep breast infections (e.g., tuberculosis)
• Secondary metastasis (e.g., melanoma, lung cancer)
• Cystosarcoma phyllodes

Diagnostic Investigations

Imaging

• Mammography : Best for detecting early breast cancer and microcalcifications. Less sensitive in dense breasts.
• Ultrasound : Useful adjunct in younger women and distinguishing cystic vs solid masses.
• CT/MRI : Used in metastatic workup.

Tissue Diagnosis

• Fine needle aspiration (FNA) : Useful for cystic lesions, initial evaluation.
• Core (true-cut) biopsy : Provides tissue architecture, determines invasiveness.
• Histopathology : Determines estrogen and progesterone receptor status, BRCA mutation testing.

Lab Investigations

• Full blood count (FBC)
• Liver function tests (LFTs)
• Renal function (U/E/C)
• Tumor markers (CEA, CA 15-3, CA 27.29)
• Chest X-ray

Histological Types (WHO Classification)

• Non-invasive (in situ)
  • Ductal carcinoma in situ (DCIS)
  • Lobular carcinoma in situ (LCIS)
• Invasive
  • Invasive ductal carcinoma (85%)
  • Invasive lobular carcinoma (1%)
  • Mucinous carcinoma (5%)
  • Papillary carcinoma (<5%)
  • Medullary carcinoma (<5%)
• Mixed epithelial and connective tissue tumors
• Miscellaneous types

Staging of Breast Cancer

TNM Classification

• T (Tumor size/extent):
  • Tx: Not assessed
  • T0: No tumor
  • Tis: Carcinoma in situ
  • T1: ≤ 2 cm
  • T2: > 2 cm ≤ 5 cm
  • T3: > 5 cm
  • T4: Extension to chest wall/skin (including inflammatory carcinoma)
• N (Node involvement):
  • Nx: Cannot assess
  • N0: No lymph nodes involved
  • N1: Ipsilateral axillary nodes, no fixation
  • N2: Ipsilateral axillary nodes, with fixation
  • N3: Ipsilateral supraclavicular or internal mammary nodes
• M (Metastasis):
  • Mx: Cannot assess
  • M0: No metastasis
  • M1: Distant metastasis (including supraclavicular nodes)

Manchester Staging System of Breast Cancer

• Stage I:
  Tumor confined to the breast. Any skin involvement covers an area smaller than the tumor size. No lymph node involvement.
• Stage II:
  Tumor is confined to the breast but involves regional lymph nodes (axillary) or skin involvement covers a larger area than the tumor size.
• Stage III:
  Tumor involves the breast with fixation to skin or chest wall or extensive skin ulceration. Significant lymph node involvement including fixation or matted nodes.
• Stage IV:
  Distant metastasis present (lung, liver, bone, brain, etc.).

Treatment of Breast Cancer

Treatment depends on stage, tumor biology (hormone receptor status, HER2), patient factors, and preferences.

1. Surgical Management

• Breast-Conserving Surgery (Lumpectomy/Wide Local Excision):
  Removal of tumor with a margin of normal tissue, usually followed by radiotherapy. Suitable for early-stage cancers.
• Mastectomy:
  Removal of entire breast tissue. Can be simple, modified radical, or radical mastectomy depending on lymph node dissection extent.
• Axillary Lymph Node Dissection or Sentinel Lymph Node Biopsy:
  To assess and manage regional lymph node involvement.

2. Radiotherapy

• Used post breast-conserving surgery to reduce local recurrence.
• Also used for palliation in advanced or metastatic disease.

3. Systemic Therapy

• Chemotherapy:
  Used in locally advanced and metastatic disease, or high-risk early disease.
• Hormonal Therapy:
  For hormone receptor-positive cancers (Estrogen and/or Progesterone receptor positive).
  • Tamoxifen (Selective Estrogen Receptor Modulator)
  • Aromatase inhibitors (postmenopausal women)
• Targeted Therapy:
  For HER2-positive tumors, e.g., Trastuzumab (Herceptin).

4. Supportive and Palliative Care

• Symptom control for metastatic disease (pain, lymphedema).
• Psychosocial support.

Prognosis

• Early-stage breast cancer generally has a good prognosis with 5-year survival rates >90%.
• Prognosis worsens with larger tumor size, lymph node involvement, distant metastasis, and unfavorable tumor biology (triple-negative, HER2-positive without therapy).
• Hormone receptor positivity generally indicates better prognosis due to available targeted therapies.

Molecular and Genetic Considerations

• Estrogen Receptor (ER) and Progesterone Receptor (PR) status:
  Guide hormonal therapy.
• HER2 (Human Epidermal growth factor Receptor 2):
  Overexpression/amplification seen in ~20% breast cancers. Targetable with monoclonal antibodies.
• BRCA1 and BRCA2 mutations:
  Genetic mutations increasing risk of breast and ovarian cancers. Implications for screening and preventive strategies.

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