Breast
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Breast Cancer
Etiology & Risk Factors
The development of breast cancer is a multifactorial process involving hormonal exposure,
genetic susceptibility, and environmental triggers.
genetic susceptibility, and environmental triggers.
Hormonal & Lifestyle Factors
- Estrogen Exposure: Prolonged exposure due to early menarche (55 years), nulliparity, or late age at first birth.
- Exogenous Hormones: Long-term use of combined Hormone Replacement Therapy (HRT).
- Lifestyle Triggers: High alcohol consumption, obesity (particularly post-menopausal), and sedentary behavior.
Genetic Predispositions
- High-Penetrance Genes: Mutations in BRCA1 and BRCA2 remain the most significant, carrying a 50–80% lifetime risk. PALB2 is now recognized as a "third major" breast cancer gene.
- Moderate-Penetrance Genes: Mutations in ATM, CHEK2, and BARD1.
- Rare Syndromes: Li-Fraumeni Syndrome (TP53), Cowden Syndrome (PTEN), and Peutz-Jeghers Syndrome (STK11).
Breast Density
- High mammographic density is both a risk factor and a diagnostic challenge, as it can mask small lesions.
Clinical Manifestations
Early-stage breast cancer is often clinically silent and detected only through screening.
Early-Stage Symptoms:
- Painless Mass: Usually hard, irregular, and non-mobile.
- Skin Alterations: Dimpling (tethering) or indentation of the skin.
- Nipple Changes: Recent-onset nipple retraction, crusting (Paget’s disease of the breast), or spontaneous bloody discharge.
Advanced-Stage Symptoms:
- Peau d’orange: Skin thickening and pitting resembling an orange peel, indicative of inflammatory breast cancer or lymphatic obstruction.
- Ulceration: Fungating mass breaking through the skin.
- Axillary Lymphadenopathy: Palpable, matted nodes in the axilla or supraclavicular fossa.
- Metastatic Symptoms: Bone pain, dyspnea (lung mets), or jaundice (liver mets).
Paraneoplastic Syndromes:
Rare, but can include Hypercalcemia of malignancy or Paraneoplastic Cerebellar Degeneration.
Diagnostic Workup
Diagnostic accuracy relies on the
“Triple Assessment”: Clinical Examination, Imaging, and Pathology.
“Triple Assessment”: Clinical Examination, Imaging, and Pathology.
Imaging:
- Digital Breast Tomosynthesis (DBT/3D Mammography): The current standard for screening and diagnostic triage.
- Contrast-Enhanced Mammography (CEM): highly sensitive alternative to MRI for evaluating the extent of disease.
Pathology (The Gold Standard):
- Core Needle Biopsy (CNB): Mandatory to distinguish invasive from in situ disease and to perform biomarker testing. Fine Needle Aspiration (FNA) is generally insufficient for primary diagnosis.
- Biomarker Testing: Routine assessment of ER (Estrogen Receptor), PR (Progesterone Receptor), and HER2 (Human Epidermal Growth Factor Receptor 2).
- HER2-Low Category: In 2026, pathologists now explicitly report "HER2-Low" (IHC 1+ or IHC 2+/ISH-) to qualify patients for targeted Antibody-Drug Conjugates (ADCs).
Liquid Biopsies:
- Utilized for monitoring ctDNA (Circulating Tumor DNA) in the adjuvant setting to detect molecular relapse months before imaging becomes positive.
Common Investigations & Staging
Staged using breast MRI for sensitive primary mapping, axillary ultrasound with biopsy for nodal assessment,
and FDG PET-CT for advanced or metastatic disease.
and FDG PET-CT for advanced or metastatic disease.
Imaging Modalities & Rationale
- Breast MRI: The most sensitive modality. Used for high-risk screening, evaluating occult primary tumors, and assessing the extent of disease in dense breasts or lobular carcinoma.
- Axillary Ultrasound: Essential for assessing regional lymph nodes; if suspicious, ultrasound-guided FNA/biopsy is performed.
- FDG PET-CT: Not routine for early disease. It is the preferred modality for initial staging of Stage III (locally advanced) disease and for evaluating treatment response in metastatic settings.
Treatment Overview
Managed through localized surgery and targeted radiotherapy, paired with subtype-specific systemic
treatments like HER2 targeted drugs, endocrine therapy, and immunotherapy.
treatments like HER2 targeted drugs, endocrine therapy, and immunotherapy.
1. Surgery
- Breast-Conserving Surgery (BCS): Lumpectomy or Wide Local Excision, typically followed by radiotherapy.
- Mastectomy: Skin-sparing or nipple-sparing mastectomy is preferred when oncologically safe, often combined with immediate reconstruction.
- Axillary Management: Sentinel Lymph Node Biopsy (SLNB) is the standard for clinically node-negative patients. Axillary Lymph Node Dissection (ALND) for clinically node-positive patients.
2. Radiotherapy
- Whole Breast Irradiation (WBI): Standard after BCS.
- Undissected Axilla as indicated.
- Hypofractionation: delivering higher doses over a shorter period (e.g., 1–3 weeks).
- Partial Breast Irradiation (PBI): An option for low-risk, older patients.
3. Systemic Therapy
- Targeted Therapy:
- HER2-Targeted: Trastuzumab and Pertuzumab.
- ADCs: Trastuzumab deruxtecan (T-DXd) and Sacituzumab govitecan have revolutionized treatment for HER2-positive, HER2-low, and Triple-Negative subtypes.
- Endocrine Therapy: Selective Estrogen Receptor Modulators (Tamoxifen) or Aromatase Inhibitors (Letrozole/Anastrozole).
- CDK4/6 Inhibitors (Abemaciclib) for high-risk HR+ disease.
- Immunotherapy: Pembrolizumab is standard in the neoadjuvant setting for Triple-Negative Breast Cancer (TNBC).
Emerging Therapies
- HER3-Targeted ADCs: Patritumab deruxtecan is entering the clinical landscape for tumors expressing HER3, providing a new line of defense for resistant cases.
- AI-Personalized Screening: AI algorithms now synthesize genetic risk, breast density, and history to create a personalized "Screening Frequency Score," moving away from generic annual guidelines.
- Oral SERDs: Next-generation oral Selective Estrogen Receptor Degraders (like Elacestrant) are replacing traditional injections for patients with ESR1 mutations in the metastatic setting.
Medical Disclaimer
This guide is for professional medical information purposes only and should not replace clinical judgment.
Treatment protocols are subject to change based on emerging data from NCCN, ASCO, and international oncology boards.
Treatment protocols are subject to change based on emerging data from NCCN, ASCO, and international oncology boards.