JC76 (Surgery) - Breast cancer Flashcards
Modalities of breast cancer spread
Direct spread
•Chest wall
•Skin and subcutaneous tissues
Lymphatic spread
oLateral tumours in outer quadrant and centrally located lesions Axillary LN
oUpper and lower inner quadrant Internal mammary LN
oSupraclavicular LN
Hematogenous spread
•Distant metastasis to lungs, liver, bone…etc
Breast cancer risk factors
- Non-modifiable RF
- Relevant PMH
Non-modifiable:
- Advanced age
- Female gender (M : F = 1 : 2000)
- White ethnicity
- Inherited BRCA1 and BRCA2 mutation
- Early menarche <12 and Late menopause >55
Medical history" High estrogen exposure - Nulliparity, no breast feeding - Late age of first pregnancy >30 - Estrogen-secreting ovarian tumor - Oral contraceptives and HRT - Obesity in post-menopausal
Breast diseases:
- History of breast cancer
- History of benign breast disease: ADH, ALH
Breast cancer risk factors
- Drug hx
- Family hx
- Social hx
Drug history
• Exposure to therapeutic ionizing radiation
Family history
• History of breast cancer
• Li-Fraumeni syndrome
Germline abnormalities of TP53 gene
Tendency to develop malignancy including breast cancer, sarcoma, brain tumours,adrenocortical cancer and leukemia
• Hereditary diffuse gastric cancer
Germline mutation of CDH1 gene
Associated with development of lobular breast cancer
Social history
• Smoking
• Alcoholism
Ddx breast cancer
Benign breast lesions
Paget disease of the nipple
Phyllodes tumours
Breast sarcoma
Lymphoma - mainly non-Hodgkin lymphoma B-cell
Paget disease of nipple
- Characteristic skin features
- Disease associated
- Clinical presentation
- Workup
characterized by eczematoid changes and ulcerated lesions ofnipple-areolar complex
80% associated with HER2 +ve breast cancer
Presents with pain, burning, pruritus, palpable breast mass, bloody nipple discharge or nippleinversion
Workup:
Mammography is mandatory to look for associated mass
USG with biopsy of any mass
Describe structure of breast
Breast comprises 3 major structures including skin, subcutaneous tissue and breast tissue
Breast tissue is composed of epithelial and stromal elements
o Epithelial components include ducts that connect structural and functional units of the breast (lobules) to the nipple
o Stromal components include adipose tissues and fibrous connective tissues
Lobules are separated by suspensory ligament of breast (Cooper’s ligament)
Arterial supply of breast
Venous drainage of breast
Arterial:
Internal thoracic (internal mammary) artery (from subclavian artery)
Lateral thoracic (external mammary) artery (from axillary artery)
Posterior intercostal artery
Thoracoacromial artery
Axillary artery
Venous Internal thoracic vein Lateral thoracic vein Posterior intercostal vein Axillary vein
Lymphatic drainage of breast
Axillary lymph node (75%)
Internal mammary lymph node (20%)
Define the axillary lymph node levels and location
Level I - Inferior and lateral to pectoralis minor muscle - Anterior, posterior and lateral axillary nodes
Level II - Posterior to pectoralis minor muscle and below the axillary vein - Central axillary nodes, Interpectoral nodes
Level III - Medial to pectoralis minor extending up to apex against chest wall (Infraclavicular) - Apical axillary nodes/ Subclavian
List the motor nerves that supply the muscles under the breast
Motor nerves
o Thoracodorsal nerve > Supply latissimus dorsi muscle
o Long thoracic nerve > Supply serratus anterior muscle
o Medial and lateral pectoral nerve > Supply pectoralis major and minor muscles
List Non-invasive and Invasive histological types of breast cancer
List histological subtypes with good prognosis, and poor prognosis
Non-invasive:
- Ductal carcinoma-in-situ (DCIS)
- Lobular carcinoma- in-situ (LCIS)
Invasive
- Invasive ductal carcinoma (IDC)
- Invasive lobular carcinoma (ILC)
Good prognosis • Tubular carcinoma • Medullary carcinoma • Mucinous (colloid) carcinoma • Papillary carcinoma
poor prognosis • Mixed ductal/lobular carcinoma • Metaplastic carcinoma • Micropapillary carcinoma • Inflammatory breast cancer
DCIS
- Presentation
- Tumor characteristics
- Treatment options
Presentation: asymptomatic or painless mass, incidental finding on mammography with microcalcifications
Tumor:
- From lobules and terminal ducts of breast with ductal predominance, confined to basement membrane
- E-cadherin + ve ***
Treatment:
Surgical:
- Partial mastectomy for unicentric lesion
- Total mastectomy for multicentric lesion
Axillary LN: DCIS is non-invasive!
- ALND not indicated for pure DCIS
- Sentinel LN biopsy for high-grade histology
Adjuvant radiotherapy for partial mastectomy
Adjuvant hormone therapy for ER+ve DCIS
LCIS
- Presentation
- Tumor characteristics
- Treatment options
Presentation: Asymptomatic/ incidental finding by mammography
Tumor characteristics:
- No microcalcifications (easily missed), from lobules and terminal ducts with lobule predominance
- Non-invasive except for Pleomorphic LCIS
- E-cadherin -VE
Treatment options: No considered cancer or pre-invasive lesion
- Lifelong surveillance
- Chemoprevention with Tamoxifen, Raloxifene, Aromatase inhibitor
- Bilateral total mastectomy for strong family history
2 most common types of invasive breast cancer
Invasive ductal carcinoma (IDC)
Accounts for 70 – 80% of invasive breast cancers (most common)
Invasive lobular carcinoma (ILC)
Accounts for 5 - 10% of invasive breast cancers (second most common)
IDC vs ILC
Histological differences
- Metastasis tendencies
Histological differences
- IDC: Cords and nests of cells with varying amount of gland formation
- ILC: Smalls cells that infiltrate mammary stroma and adipose tissue in a single file pattern
Metastasis tendencies
- IDC: A/w DCIS, Earlier than invasive lobular carcinoma (ILC)
- ILC: Later than invasive ductal carcinoma (IDC), Metastasize to unusual location including meninges, gastrointestinal tract and peritoneum
Diagnostic criteria of inflammatory breast cancer
o Rapid onset of breast erythema, edema, peau d’ orange or warm breast with or without an underlying palpable breast mass
o Erythema occupying at least 1/3 of the breast
o Duration of history no more than 6 months
o Pathological confirmation of invasive carcinoma
Atypical ductal hyperplasia vs Atypical lobular hyperplasia (ADH/ ALH)
Cell origins
Treatment options
Proliferative lesions with cellular atypia that arises from breast ducts (ADH) and lobules (ALH) respectively
Treatment: Both with risk of malignant transformation
- Core Biopsy for both
- Excisional biopsy if core biopsy finds atypical hyperplasia
- Treat like DCIS/ IDC or LCIS/ ILC if malignant
- Or lifelong surveillance with chemoprevention (Tamoxifen) if not malignant
List 3 major molecular subtypes of breast cancer
Prevalence of each type?
Depends on ER, PR, HER2 expressions:
Luminal A and B - 70% of breast cancer
- Luminal A: ER, PR +ve
- Luminal B: Triple Positive
HER2 - 15% of breast cancer
Basal-like/ Triple negative: 15% of breast cancer
Luminal A/B, HER2, Basal-like breast cancer
Treatment choice for each
Luminal A/B: Hormone treatment
HER2: Anthracycline-based chemotherapy or Herceptin
Basal-like/ Triple negative: Platinum/ PARP inhibitors responsive
Surgical description of breast cancer mass
- Site: 50% of CA breast occurs in upper outer quadrant including the axillary tail
- Color: Discoloration (smooth and reddening) if tumour is close to overlying skin, Peau d’orange
- Shape: Spiculated
- Edge: Irregular or nodular
- Surface: Dimpling, tethering, erythema
- Consistency: Solid and stony hard
- Tenderness: Usually non-tender
- Mobility: Fixation of lump (Immovable)
- Lymph nodes: May be palpable and enlarged axillary LN
5D for surgical description of nipple changes
- Deviation/ Displacement
- Discoloration
- Dermatitis (Eczema in Paget’s disease of nipple)
- Depression (Retraction/ Inversion)
- Discharge
Possible skin changes over breast mass
- Lump/ nodules
- Ulceration
- Discoloration: Erythema/ Hematoma/ Ecchymosis (in fat necrosis)
- Puckering/ Dimpling: Underlying cancer
- Peau d’ orange
How to elicit skin fixation, skin tethering or muscle fixation of breast mass on P/E
o Skin fixation: Try to pick up the skin above the lump
o Skin tethering: Lump behaves as if tied to skin by a piece of string/ Remains separate from skin and can be moved independently within certain limits
o Muscle fixation: Move the lump in 2 perpendicular direction, then contract the pectoralis muscle by asking patient to press against her hip, move the lump again and observe for limited movement
Modalities of radiological imaging for breast mass
Mammogram (1st-line)
Ultrasound (2nd-line, or for younger patients with dense breasts)
MRI breast (3rd-line)
PET-CT (metastasis)
Ductoscopy
Mammogram
- 2 standard views
- Descriptors of mammogram (steps to describe)
- Limitations
craniocaudal (CC) and mediolateral oblique (MLO) views
- CC for inferior, medial and upper portion
- MLO for axillary tail, axillar lymph nodes and upper outer quadrant
Descriptors:
- Symmetry in shape and density
- Architecture distortions
- Presence of lymph nodes
- Presence of breast mass, mass density: Spiculated (stellate) mass or irregular shape for malignancy
- Any Calcification
Limitations:
- NOT preferred in young women (age < 40) due to dense breast (low sensitivity)
- Cannot make definitive diagnosis
- Obscuration of borders and extent of primary tumour by dense breast tissues
Mammogram
Features of benign vs malignant cancer
Benign: Rim-like calcification Large coarse calcifications Smooth round or oval calcifications Vascular and skin calcification
Malignant:
Pleomorphic, linear or clustered MICROCALCIFICATIONS
Ultrasound for breast mass
- Function
Determines whether the mass is solid or cystic
Characterize solid mass as benign or malignant
Identify presence of a prominent vascular supply
Image-guided procedures including FNAC or core biopsy
Ultrasound of breast tissue
Features suggesting benign lesion vs malignant lesion
- Shape
- Margin
- Echogenicity
- Calcification
- Vascularity
MRI breast
Indications
Malignant breast cancer features
High risk of breast cancer
Breast implants or augmentations
Suspicious lesions on mammogram or ultrasound
Clinically occult tumor with positive LN
Neoadjuvant therapy
MRI abnormalities (malignant features) • Spiculated or irregular margins • Rim-like enhancement • Heterogenous internal enhancement • Enhancing internal septa • More rapid uptake of contrast
Modalities of imaging for breast cancer metastasis
CXR for lung metastasis USG abdomen for liver metastasis Bone scan for bone metastasis CT abdomen for liver, adrenal and ovarian metastasis CT or MRI brain for brain metastasis
Criteria and test for breast cancer HER2 expression
o Immunohistochemistry (IHC 3+) defined as uniform intense membrane staining of ≥ 10% of tumour cells by
(OR)
o Presence of HER2 gene amplification by fluorescence-in-situ-hybridization (FISH) defined as:
- ratio of HER2/CEP17 ratio ≥ 2.0
- (OR) HER2/ CEP17 ratio < 2.0 with average HER2 copy number ≥ 6 signals/ cell
Prognosis of HER2+ breast cancer
- Higher risk of recurrence
- Higher mortality
- Relative resistance of hormonal treatment
- Less benefit from some forms of chemotherapy
Sampling methods for palpable and non-palpable breast cancer
Methods of biopsy for palpable lumps
• Fine needle aspiration (FNA)
• Core biopsy (Trucut biopsy)/ Vacuum-assisted biopsy
• Excisional and incisional biopsy
Methods of biopsy required for NON-palpable lumps = Image-guided biopsy required with Hook-wire guided excision o Stereotactic (X-ray guidance) o Ultrasound (USG) o MRI-guided
Compare FNAC and core biopsy for breast cancer
- Advantages and disadvantages
IHC score for protein overexpression in breast cancer
Scoring and histological description
Outline flowchart for HER2 FISH testing for breast cancer
- Criteria for ISH positive or negative
Modalities of treatment for breast cancer
Local disease:
o Surgery
o Radiotherapy
Systemic/ metastatic disease:
o Chemotherapy
o Hormonal therapy
o Targeted therapy
Treatment options for DCIS and LCIS breast cancer
DCIS: Van Nuys Prognostic Index • Low score = Wide local excision • Intermediate score = Wide local excision + Radiotherapy • High score = Mastectomy Lymph node management • Sentinel lymph node biopsy (SLNB) • Axillary lymph node dissection (ALND) Systemic: Adjuvant radiotherapy or hormonal therapy
LCIS:
Bilateral simple mastectomy with reconstruction
Tamoxifen prophylaxis
Treatment for stage 1-3 breast cancer
Surgical approach
• BCT (OR)
• Mastectomy with reconstruction
Lymph node management
• Sentinel lymph node biopsy (SLNB) (OR)
• Axillary lymph node dissection (ALND)
± Adjuvant chemotherapy
± Adjuvant radiotherapy
± Adjuvant hormonal therapy
± Adjuvant targeted therapy
Treatment for stage 4 breast cancer
Palliative chemo, radio, hormonal or targeted therapy
Modalities of breast cancer screening
Which modalities are outdated/ poor detection rate
Self- breast examination - not recommended
Clinical breast examination - no improvement on survival
Mammogram - 20% reduction in mortality, especially pt. over 50 years old
Harms of mammogram screening
Over diagnosis (false positive) and over treatemtn
False reassurance (false negative)
Radiation exposure
Pain and discomfort during scan
Indication for breast cancer screening in HK
Age: 44-69
Risk factors:
- Family history of breast cancer (1st degree cousin)
- Previous benign breast disease
- Nulliparity
- Late age of one live birth
- Early menarche and late menopause
- High BMI and low physical activity
Mammogram screening every 2 years
Triple assessment of breast cancer
- Which 3 parts
Clinical exam: history and examination
Radiological exam
Pathological exam
Surgical mastectomy
- All types
Simple mastectomy (Linear scar)
Radical masectomy
Modified radical masectomy
Skin sparing mastectomy with reconstruction
Nipple sparing mastectomy with reconstruction (low risk or prophylaxis)
Surgical lumpectomy
- Margin cut-off
2mm for in-situ cancer
No cancer at inked margin for invasive cancer
Histological margin determined intra-operatively, aim for 5-10mm margins
Oncoplastic breast surgery
- Different surgeries are different volume displacement and replacement
Level I: <20% breast tissue removed
- Local tissue rearrangement
- Crescent or Doughnut mastopexy
Level II: 20-50% breast tissue removed
- Circumvertical mastopexy
- Reduction mammaplasty
Volume replacement
> 50% breast tissue removed
- Implant-based reconstruction
- Local/ regional flap reconstruction
Axillary dissection for breast cancer
- Indications
- Levels of LN removed
- Preserved structures
- Complications
Indications:
• Clinically +ve nodes
• Sentinel lymph node +ve nodes
• Inflammatory breast cancer (T4d)
Level I and II axillary LN removed (≥ 10 lymph nodes)
Preserved:
- Long thoracic nerve - serratus anterior - winging scapula
- Thoracodorsal nerve - latissimus dorsi - shoulder extension
- Intercostobrachial nerve - axilla parasthesia
Complications:
- Seroma
- Lymphedema
- Nerve injury
- General surgical complications (infection, pain…etc)
- Shoulder dysfunction/ Restricted shoulder mobility
Sentinel LN biopsy
- Identification methods
- Indications
Identify by:
- Blue dye/ Patent blue
- Radioisotope
- Supramagnetic iron oxide
- Indocyanine green
Indications:
- Early breast cancer with clinical -ve nodes
- DCIS with planned mastectomy
- DCIS with suspicious features (> 5 cm or present with a palpable mass)
Breast reconstruction choices
- types of surgery
- Types of flaps
Autologous tissue reconstruction
o TRAM flap: Transverse rectus abdominal muscle (weaken abdominal muscle)
o LD flap: Latissimus dorsi muscle
o DIEP flap: Deep inferior epigastric perforator (preserve abdominal muscle)
Prosthetic devices
o Devices include saline implants, silicone implants or tissue expanders
Targeted therapy for breast therapy
- Options
Trastuzumab (Herceptin)
• IV infusion monthly for 12 months
Lapatinib
Bisphosphonates/ Denosumab (RANKL monoclonal antibody)
• Osteoclast inhibitors
• Indicated for palliation in patients with bone metastasis
Hormonal therapy options for breast cancer
Selective estrogen receptor modulators (SERMs) - Indicated in all ER or PR +ve patients
Example: Tamoxifen
Aromatase inhibitors (AI) Non-steroidal: - Letrozole - Anastrozole Steroidal: - Exemestane
Selective estrogen receptor modulators (SERMs)
MoA
S/E
Mechanism of action
• Antagonist of ER receptor at breast
• Inhibits growth of breast cancer cells by competitive antagonism of ER
S/E: Thromboembolic disease* • Stroke • Deep vein thrombosis (DVT) • Pulmonary embolism
Endometrial cancer*
• Partial agonist of ER receptor at uterus
Menopausal symptoms
• Hot flushes
• Tachycardia and sweating
Vaginal discharge, Menstrual irregularities, Sexual dysfunction
Aromatase inhibitor
MoA
S/E
Mechanism of action
• Inhibits peripheral conversion of testosterone and androstenedione to estradiol
Appropriate for post-menopausal women ONLY
S/E Osteoporosis* Associated musculoskeletal syndrome • Bone pain • Arthralgia • Joint stiffness
Radiotherapy for breast cancer
- Types
- Indications
Whole breast radiation therapy (WBRT):
Indications
• ALL patients undergoing breast conservation surgery (BCT)
• Post-mastectomy patients with high-risk features
Regional nodal irradiation
Indications
• Node +ve disease with ≥ 4 involved lymph node
• Node -ve T2 tumour with features such as high-grade tumour, high risk receptor biology or lymphovascular invasion
• T3 or T4 primary tumour
Complications of breast radiotherapy
Whole breast radiation therapy (WBRT)
Short-term complications o Breast skin fibrosis, radiation dermatitis o Arm edema Long-term complications o Rib fracture o Cardiotoxicity o Pulmonary fibrosis or pneumonitis o Secondary RT-induced malignancy
Regional nodal irradiation
Complications
• Lymphedema
• Axillary fibrosis
