Breast Cancer 😍

Increased Risk

• Non-modifiable:
• Increasing Age.
• Female gender.
• Family history.
• Genetic mutations (BRCA).
• Early menarche, late menopause.

• Hormonal/Reproductive:
• Nulliparity (no childbirth).
• Maternal age at first live birth >30 yrs.
• HRT (estrogen + progesterone).

• Lifestyle:
• Smoking.
• Smoking a/w breast conditions:
• Cancer
• Duct ectasia
• Mondor disease
• Periductal mastitis
• Obesity
• Alcohol consumption

Decreased Risk

• Breastfeeding (for >1 year).

• Maternal age at first live birth <20 years.

Microcalcification:

• Highly suspicious of cancer.

• Needs biopsy.

• Corresponds to BIRADS 5.

• In decreasing order of risk of malignancy-
• Cluster microcalcification (maximum risk)
• Linear microcalcification
• Segmental microcalcification
• Diffuse microcalcification (minimum risk)

• Note
• Microcalcification → Suggests Malignancy
• Popcorn calcification → Fibroadenoma

Ivory vertebrae.

• Seen in
• Pagets disaese
• Hodgkins Lymphoma
• Blastic mets
• Breast Ca
• Prostate Ca
• HOD Page il Ivory kuthi vach

Q. Benign or malignant?:

• Malignancy:
• Irregular/spiculated margins.
• Taller > Wider.

Pathophysiology

Features & Genetics

• Most Common Type:
• Invasive ductal carcinoma (IDC).
• Origin: Terminal duct lobular unit (TDLU).

• Quadrants Affected:
• Most common → Upper outer.
• Least common → Lower inner.

Gene Mutations:

• BRCA 1 (Chr 17q):
• BRCA 1 > 2 :
• Breast cancer
• Ovarian cancer.

• BRCA 2 (Chr 13q):
• BRCA 2 > 1 :
• Breast
• Pancreatic
• Prostate
• Male breast cancer.

Staging & Metastasis

TNM Staging

• N1 to N3c → all I/L

• If C/L nodes → M1

Metastasis

• Most Common Site: 
• Lumbar Vertebrae: 
• Most common bony site due to Batson's plexus

• Bony Metastasis Type: 
• Osteolytic > osteoblastic

• Lobular carcinoma insitu is no longer in situ cancer

• Most imp prognostic factor
• Axillary lymph node status

Molecular Subtypes (Based on IHC)

• Ki-67/ MIB 1:
• Proliferation index marker.

Epithelial–Mesenchymal Transition and E-cadherin

• EMT ⇒ ↓ E-cadherin / Claudin

• Driven by SNAIL, SLUG, TWIST, ZEB1/2

Immunohistochemistry (IHC)

ER, PR:

• Diaminobenzidine → Impart brown color

• Nuclear staining (brown color).
• Bcz steroid receptors
• Dot dot staining

• Measures with Allred score → 0 - 8
• positive if 1% cells are brown.
• Uniform homogenous staining

HER2 neu:

• Membranous staining (brown color).

• Batson plexus → From Prostate and Breast → To Bones

• Trastuzumab → cardiotoxic

Breast Conservative Surgery (BCS)/Lumpectomy

• Procedure: Tumour removal with 1 mm margin

• Post-Surgery: 
• Mandatory radiotherapy (due to increased local recurrence rate)

Oncoplasty

1. Volume Displacement (Round Block Technique): 

• 10-15% of breast volume resected

2. Volume Replacement: 

• >15% of breast volume resected

• Can use Latissimus Dorsi (LD) flap

Contraindications for BCS

• Contraindications for Radiotherapy (RT):
• Pregnancy
• Prior RT to chest wall
• Collagen vascular disease (e.g., SLE, rheumatoid arthritis)

• Technical Contraindications:
• Multicentric disease > Multifocal
• Lobular cancer (if multicentric)
• Large tumour-to-breast ratio
• Locally advanced breast cancer (LABC)

• Relative Contraindications:
• Multifocal disease

Mastectomy

Radical/Halsted Mastectomy:

• Structures Removed:
• Breast, Nipple Areolar Complex (NAC)
• Level 1, 2, 3 axillary lymph nodes
• Pectoralis major & minor

Modified Radical Mastectomy (MRM):

• Incision: Elliptical Stewart incision

• Structures Removed:
• Breast + NAC
• Level 1, 2, 3 axillary lymph nodes (LN)
• Pectoral fascia
• ± Pectoralis minor
• Retracted: Auchincloss (Most Common)
• Cut: Scanlon (incise), Patey (remove)

Simple Mastectomy:

• Structures Removed: Breast + NAC

• LN: Not removed

• Usage: Toilet/palliative mastectomy for fungating breast cancer

Axillary LN Clearance

• M/c N injury → Intercoastal Brachial trunk (ICBT)

 

• Minimum LNs Removed: 10

• Nerves Saved During Axillary clearance:
• Medial pectoral nerve
• Laterally located
• Pierces pectoralis minor
• Lateral pectoral nerve
• Medially located
• Runs anterior to pectoralis minor



 
• Long thoracic nerve (Not a boundary)

• Boundary
• Superiorly → Axillary vein
• Inferiorly → Angular vein
• Laterally → Thoracodorsal pedicle
• Medially → Halstead ligament

• AVOIDED IF BCS IS PLANNED
• (RISK OF LYMPHEDEMA WHEN COMBINED WITH RADIOTHERAPY)

Level	Location	Groups
I	Lateral to pectoralis minor	Anterior, lateral, posterior (subscapular)
II	Superficial or deep to pectoralis minor	Central, interpectoral
III	Medial to pectoralis minor	Apical (subclavicular)

Complications of Modified Radical Mastectomy (MRM)

• Haemorrhage

Seroma (Fluid Accumulation):

• Most common complication

• Prevention: Romovac drain

• Management: Aspirate under aseptic conditions

Nerve Injury:

• Intercostobrachial Nerve
• Most Common Nerve Injured
• Numbness + paraesthesia in axilla
• Phantom breast syndrome

• Long Thoracic Nerve/Nerve of Bell:
• Winging of scapula

Lymphedema (Post-Mastectomy) of Upper Limb:

• Most common cause of upper limb lymphedema

• Develops weeks to months post-surgery

Recurrence:

• Local: 
• IOC: MRI
• Biopsy

• Diffuse: 
• Cancer en curasse
• Diffuse erythema
• Plaque like thickening involving chest wall and abdominal skin

Stewart-Treves Syndrome/Lymphangiosarcoma

• Development:
• Angiosarcoma
• Long Standing (8-10 years) Lymphedema

• Features:
• Bluish/reddish skin nodules.

• Increased Incidence: 
• LN removed above axillary vein
• RT given to axilla after clearance

Reconstructive Surgery

TRAM Flap (Transverse Rectus Abdominis Myocutaneous Flap):

• Increased abdominal wall morbidity (muscle removed)

• Uses muscle

• ↑ risk of incisional hernias

• Mnemonic: traM → has M → Muscle in it

DIEP Flap (Deep Inferior Epigastric Artery Perforator Flap):

• Best flap for breast reconstruction

• Only skin + fat

• Decreased abdominal wall complications (muscle not removed)
• No abdominal wall weakness

Sentinel Lymph Node Biopsy (SLNB)

• Definition: 
• First draining LN in cancer (First described by Cabana)
• Done when clinically node negetive in BCS
• In MRM LN is always removed

• Most Common Nerve Injured: 
• Intercostobrachial nerve

• Cancers Where SLNB is Used:
• Malignant melanoma
• Breast cancer
• Penile cancer
• Vulval cancer
• Head & neck cancer

Identification Methods:

• Blue Dye Technique:
• Isosulfan blue/methylene blue dye used
• Injected in periareolar region (subcutaneous plane)
• Complications:
• Skin tattooing (Most Common)
• Anaphylaxis
• Bluish discolouration of urine

• Radionuclide Technique:
• Tc99 tagged sulphur colloid injected (periareolar region)
• Sulphur for SNLB
• Hot nodes (radioactive) identified on gamma camera

• Indigocyanine Green (ICG): 
• New method

• Dual Technique (Best): 
• Blue dye + Radionuclide OR
• Blue dye + ICG

Chemotherapy

• Indications:
• LN +
• LABC
• ER -, PR -
• HER2 neu +

• Neoadjuvant Chemotherapy (NACT) Indications:
• LABC
• Large tumour with patient desirous of BCS
• Triple-negative breast cancer (TNBC)
• HER2 neu +

Response Evaluation Criteria in Solid Tumours (RECIST):

• Single largest diameter (SLD) measured to assess tumour shrinkage

Response Type	Definition
Complete Response (CR)	Disappearance of all lesions + pathologic LN
Partial Response (PR)	≥ 30% decrease in SLD
Progressive Disease (PD)	≥ 20% increase in SLD despite chemotherapy OR new lesions forming
Stable Disease	Neither PR nor PD

• Documenting Stage After Chemotherapy: 
• Before chemo → T3N1M0
• After chemo → y c T2 N0 M0
• 'y' indicates after neoadjuvant chemotherapy
• 'c' indicates clinical stage

Avoidance of Chemotherapy: 

• Patient not fit for chemotherapy

• poor performance status (ECOG/Karnofsky)

• Early breast cancer (T1, T2/N0/m0) + Luminal A → No chemoRx.
• Hormone positive + HER-2 neu (-) + Ki67 low

Chemoport: 

• Tip lies in SVC above right atrium

Radiotherapy

• Indications:
• LN +
• Tumour >5 cm
• LABC
• After BCS

Hormonal Therapy

• Usage: Only given in ER +, PR + breast cancers

Premenopausal:

• Drug: 
• SERM → Tamoxifen

• Duration: 10 years

• Side Effects:
• Hot flashes (Most Common)
• DVT
• Endometrial hyperplasia

Postmenopausal:

• Drug: Aromatase inhibitor (Letrozole/anastrozole)

• Duration: 10 years

• Side Effects: Osteoporosis (Most Common)

• S/E
• Trastuzumab → cardiotoxic
• Tamoxifene → Endometrial hyperplasia
• Letrozole → Osteoporosis

ER il - Premen girl - we Tame (Tamoxifen) - Postmen girl - she Let (Letrozole/Anastrozole) in, but Full Elastic (Elacestrant)

Her 2 → Her hole - Tight (Tratzumab) → Lap (Lapatinib) Peruthu (Perutuzumab) Neeradichu (Neratinib)

TNBC → Threesome → Do (Doxor) in Car (Carboplatin) 4 Paisa (Paclitaxel) at Olaparambu (Olaparib) with Wife (Pembrolizumab)

Treatment Summary