Breast Cancer Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Breast cancer is the most common cancer among Malaysian women, accounting for nearly 18% of all cancer cases. Crucially, the Malaysia National Cancer Registry (2017-2021) shows a worrying trend: over 50% of our patients are diagnosed at late stages (Stage III & IV), which directly impacts survival.
High-Yield Definition: Breast cancer is a malignancy arising from the epithelial cells of the ducts or lobules of the breast. Its clinical behaviour and prognosis are determined by its histological type, grade, and the expression of specific molecular markers (hormone receptors and HER2).
Clinical One-Liner: Basically, it's an uncontrolled growth of breast cells, most often presenting as a painless lump, that we must work up urgently to rule out malignancy and stage appropriately.
II. Etiology & Risk Factors
Etiology: The development of breast cancer is multifactorial, involving a complex interplay between genetic predisposition and hormonal and environmental factors that lead to malignant transformation of breast epithelial cells.
Risk Factors (Relevant to Malaysia):
Non-modifiable:
Female gender: The primary risk factor.
Increasing age: Peak incidence in Malaysia is between 60-64 years.
Genetic predisposition: Family history of breast or ovarian cancer, especially in a first-degree relative. Documented mutations in BRCA1, BRCA2, PALB2, etc.
Early menarche (<12 years) / Late menopause (>55 years): Longer lifetime estrogen exposure.
Dense breast tissue on mammography.
Modifiable:
Nulliparity or late age at first childbirth (>30 years).
Limited or no breastfeeding.
Postmenopausal obesity: A significant factor in our population with rising NCD rates.
Hormone replacement therapy (HRT).
Alcohol consumption.
III. Quick Pathophysiology
In simple terms, normal breast cells acquire genetic mutations that disrupt the cell cycle. This allows them to divide uncontrollably, forming a primary tumour. These cancer cells can then invade surrounding breast tissue, enter lymphatic vessels to reach axillary nodes, or penetrate blood vessels to metastasize to distant sites like the lungs, liver, bones, and brain. The expression of Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) on the cell surface are critical drivers for many of these tumours and are our main targets for systemic therapy.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Hard, irregular, immobile breast lump: Action → Urgent referral to Surgical/Breast Clinic for Triple Assessment.
Signs of locally advanced disease (Peau d'orange, skin ulceration, chest wall fixation): Action → Counsel patient on probable diagnosis, perform staging investigations concurrently with biopsy.
Palpable supraclavicular or matted axillary lymph nodes: Action → High suspicion for nodal metastasis; ensure this is sampled during workup (FNA/biopsy).
Symptoms of distant metastases (e.g., persistent bone pain, unexplained seizures, jaundice): Action → Alert senior, prioritize staging imaging (e.g., CT scan, bone scan) alongside primary breast workup.
History:
Common (>50%): A new, painless, palpable breast lump.
Less Common (10-50%): Nipple discharge (especially if bloody or unilateral), nipple retraction or inversion, skin changes (dimpling, tethering), breast pain (mastalgia is usually benign, but cancer must be excluded).
Pertinent Negatives: Ask about recent trauma (to exclude fat necrosis), fever or signs of infection (to exclude abscess), and cyclical changes with menstruation (suggests benign fibrocystic change).
Physical Examination:
Inspection (patient sitting up, arms by side, then raised): Look for asymmetry, skin changes (erythema, dimpling, peau d'orange), nipple changes, visible masses.
Palpation (patient supine, hand behind head on the side being examined): Systematically palpate all four quadrants and the retroareolar area. Describe any lump: site, size, shape, consistency (hard/firm), margins (irregular/smooth), mobility (mobile/tethered to skin or chest wall).
Nodal Examination: Carefully palpate the axillary lymph nodes (anterior, posterior, lateral, central, apical groups) and the supraclavicular fossa.
Clinical Pearl: Always examine the contralateral breast. It serves as a baseline for comparison and can harbor synchronous disease.
V. Diagnostic Workflow
Differential Diagnosis:
Fibroadenoma:
Points For: Common in younger women (<30), smooth, mobile, well-defined, "breast mouse".
Points Against: Hardness, irregularity, skin changes, older age group.
How to Differentiate: Ultrasound typically shows a well-circumscribed, hypoechoic mass. Core biopsy is definitive.
Fibrocystic Changes:
Points For: Often multiple or bilateral lumps, tender, fluctuates with menstrual cycle.
Points Against: A persistent, dominant, hard lump.
How to Differentiate: Clinical follow-up post-menses can show resolution. Ultrasound may show simple or complex cysts.
Breast Abscess:
Points For: Pain, erythema, warmth, fluctuance, systemic signs of infection (fever). Often associated with lactation.
Points Against: Lack of inflammatory signs, chronic presentation.
How to Differentiate: Ultrasound will show a complex fluid collection. A trial of antibiotics and/or aspiration can be diagnostic and therapeutic. Inflammatory breast cancer is a key differential for non-resolving mastitis.
Investigations Plan (The "Triple Assessment"):
This is the standard of care and combines clinical examination, imaging, and pathology.
Clinical Examination: As detailed above.
Imaging:
Mammogram: The primary imaging modality for women >40 years. Look for spiculated masses, architectural distortion, and suspicious microcalcifications.
Breast Ultrasound: Used for women <40 years (due to dense breast tissue) and as an adjunct to mammography to characterize lesions (solid vs. cystic) and guide biopsies.
Pathology:
Core Needle Biopsy: This is the GOLD STANDARD. It is preferred over Fine Needle Aspiration (FNA) because it provides tissue architecture. It allows us to determine:
Histology (e.g., Invasive Ductal Carcinoma, Invasive Lobular Carcinoma).
Tumour Grade.
ER, PR, and HER2 status (critical for treatment planning).
VI. Staging & Severity Assessment
We use the American Joint Committee on Cancer (AJCC) TNM Staging System (8th Edition). It incorporates not just the anatomical spread (TNM) but also tumour grade and biomarker status to define a prognostic stage.
T (Tumour): Describes the size and extent of the primary tumour (e.g., T1: ≤2 cm, T2: >2 to 5 cm, T4: extension to chest wall/skin).
N (Nodes): Describes the extent of regional lymph node involvement (e.g., N1: 1-3 axillary nodes, N2: 4-9 axillary nodes).
M (Metastasis): Describes the presence or absence of distant spread (M0: no distant metastasis, M1: distant metastasis present).
Impact on Management:
Stage 0 (DCIS): Non-invasive. Treated with surgery, often with radiation. No chemotherapy.
Stage I-II (Early Stage): Curable intent. Treatment is primarily surgery, followed by adjuvant (post-operative) radiation, chemotherapy, endocrine therapy, or targeted therapy depending on tumour characteristics.
Stage III (Locally Advanced): Disease has spread extensively to lymph nodes or surrounding tissues but not distant sites. Often requires neoadjuvant (pre-operative) chemotherapy to downstage the tumour before surgery.
Stage IV (Metastatic): Incurable, but treatable. The goal is palliation and extension of life. Management is primarily systemic (chemotherapy, endocrine therapy, targeted therapy).
VII. Management Plan
Management is decided by a Multidisciplinary Team (MDT) including surgeons, oncologists, radiologists, and pathologists.
Immediate Stabilisation (The ABCDE Plan):
Most breast cancer presentations are not acute emergencies. However, be aware of complications:
Hypercalcemia of Malignancy (in metastatic bone disease): IV fluids (Normal Saline), IV Bisphosphonates (e.g., Zoledronic acid 4mg).
Pathological Fracture: Orthopaedic consult, analgesia, immobilisation.
Spinal Cord Compression: High-dose IV Dexamethasone, urgent MRI, alert oncologist and spinal surgeons.
Definitive Treatment (The Ward Round Plan):
1. Local Control (Surgery & Radiotherapy):
Breast Conserving Surgery (BCS / Lumpectomy): Removal of the tumour with a margin of normal tissue. Almost always followed by radiotherapy.
Mastectomy: Removal of the entire breast. Radiotherapy is given if the tumour is large (>5cm) or lymph nodes are positive.
Axillary Staging: Sentinel Lymph Node Biopsy (SLNB) for clinically node-negative patients; Axillary Lymph Node Dissection (ALND) for node-positive patients.
2. Systemic Control (Adjuvant/Neoadjuvant Therapy):
Chemotherapy: Used for aggressive tumours (high grade, node-positive, triple-negative, HER2-positive). Common regimens in the MOH formulary include Anthracycline-based (e.g., AC: Doxorubicin, Cyclophosphamide) followed by a Taxane (e.g., Paclitaxel).
Endocrine (Hormone) Therapy: For ER/PR-positive tumours. The backbone of treatment for this subtype.
Premenopausal: Tamoxifen 20mg OM for 5-10 years.
Postmenopausal: Aromatase Inhibitors (e.g., Letrozole 2.5mg OM, Anastrozole 1mg OM) for 5-10 years.
Anti-HER2 Targeted Therapy: For HER2-positive tumours. Dramatically improves prognosis.
Trastuzumab (Herceptin): Given with chemotherapy.
CDK4/6 Inhibitors: For high-risk, hormone receptor-positive early breast cancer.
Abemaciclib: Now available in our formulary for adjuvant treatment in node-positive, high-risk patients.
VIII. Complications
Immediate (From Surgery):
Seroma/Hematoma: Management: Aspiration if large or symptomatic.
Wound Infection: Management: Antibiotics based on local antibiogram.
Short-Term (From Treatment):
Lymphedema: Management: Physiotherapy, compression sleeves. Prevention is key.
Chemotherapy side effects (Neutropenic sepsis, mucositis): Management: Follow hospital protocols for neutropenic sepsis. Provide supportive care.
Radiodermatitis: Management: Emollients, topical steroids.
Long-Term:
Cardiotoxicity (from Anthracyclines/Trastuzumab): Management: Requires baseline and follow-up echocardiograms.
Secondary Malignancies: Small but real risk from chemotherapy/radiotherapy.
Premature Menopause / Infertility (from chemotherapy): Management: Refer to fertility specialist before starting treatment if relevant.
IX. Prognosis
Prognosis is highly dependent on the stage at diagnosis and tumour biology.
Malaysian Data (MySCan study): The overall 5-year relative survival rate is approximately 67%. This is lower than in high-income countries, largely due to late presentation.
Early Stage (I/II): 5-year survival is >85-90%.
Late Stage (IV): 5-year survival drops to ~25%.
Top 3 Prognostic Factors:
Stage at Diagnosis: (Specifically lymph node status and presence of metastases).
Tumour Biology: (Triple-negative is most aggressive; Luminal A is most indolent).
Response to Treatment.
X. How to Present to Your Senior
"Dr., for review please. This is Puan Zainab in the clinic, a 52-year-old postmenopausal lady with no known medical illness, who presented with a self-detected right breast lump for 2 months. On examination, there is a 3cm, hard, irregular lump in the upper outer quadrant with palpable axillary nodes. My main differential is breast carcinoma, likely Stage II. I am sending her for an urgent mammogram, ultrasound, and to schedule a core biopsy. I would like to ask if we should also proceed with baseline staging bloods and a CXR."
XI. Summary & Further Reading
Top 3 Takeaways:
Breast cancer is the most common cancer in Malaysian women; a high index of suspicion is mandatory for any breast lump.
The Triple Assessment (Clinical exam, Imaging, Pathology) is the cornerstone of diagnosis. A core biopsy is mandatory to confirm histology and biomarkers.
Management is complex and multidisciplinary, tailored to the cancer stage and molecular subtype (ER/PR, HER2).
Key Resources:
Malaysian CPG: Management of Breast Cancer (Third Edition), Ministry of Health Malaysia. Link
UpToDate: Search for "Clinical features, diagnosis, and staging of newly diagnosed breast cancer" and "Overview of the treatment of early-stage breast cancer."
National Cancer Registry: Summary of Malaysia National Cancer Registry Report 2017-2021 for local statistics.
