PG & Superspeciality Level Viva Questions: Long Case of Breast (Carcinoma Breast)

SECTION 1: HISTORY TAKING - VIVA QUESTIONS

• Malignant: age >35, post-menopausal, progressive increase in size, painless, hard, irregular, fixed to skin/deep fascia, associated nipple changes, axillary nodes
• Benign (fibroadenoma): young woman <30, smooth, mobile, rubbery, no skin changes ("breast mouse")

• Obesity (BMI >30): RR 1.29 in postmenopausal women
• Nulliparity or first pregnancy >35 years
• Breastfeeding <12 months (protective if >12 months)
• HRT use >10 years: RR 1.2
• Tobacco: RR 1.14 (25+ cigarettes/day)
• Alcohol: RR 1.46 (heavy drinking >4 drinks/day)
• Radiation exposure: RR 6

• Age (median 60 years in West; 48 years in India)
• Female sex (male breast cancer = 0.5-1% of all breast cancers)
• Ethnicity: American white, African American <45 years, Ashkenazi Jews, Parsis in India
• Family history: BRCA1/2 mutations, first-degree relatives
• Previous breast cancer, atypical hyperplasia on biopsy, DCIS/LCIS
• Early menarche (<12 years), late menopause (>55 years)

SECTION 2: CLINICAL EXAMINATION - VIVA QUESTIONS

1. Inspection (sitting, arms at side; arms raised; leaning forward): Look for asymmetry, skin dimpling, peau d'orange, nipple retraction/deviation/discharge, ulceration, visible veins, cancer en cuirasse
2. Palpation (supine, ipsilateral arm behind head): All four quadrants + retroareolar area + axillary tail (tail of Spence). Describe lump - site (upper outer quadrant most common - 60%), size, shape, surface, consistency, margins, tenderness, mobility (skin - tethering vs. fixation; deep - pectoral fascia involvement)
3. Axillary examination: Level I, II, III nodes; pectoral, subscapular, central nodes
4. Supraclavicular fossa examination
5. Opposite breast examination
6. Systemic examination: Spine/bone tenderness, liver size, pleural effusion, chest nodules

• Tethering: Skin moves with the lump when displaced - ligaments of Cooper are invaded but skin is not yet fixed. Sign: dimpling on attempting to displace the lump
• Fixation: Skin cannot be moved independently of the tumour - skin directly involved by tumour. Constitutes T4b (peau d'orange/oedema/satellite nodules)

• T4a: Extension to chest wall (NOT pectoral muscle alone)
• T4b: Ulceration, ipsilateral macroscopic satellite skin nodules, or peau d'orange/skin oedema
• T4c: Both T4a and T4b
• T4d: Inflammatory carcinoma (erythema + oedema involving ≥1/3 of breast skin, rapid onset)

SECTION 3: INVESTIGATIONS - VIVA QUESTIONS

1. Clinical examination (history + physical examination)
2. Imaging (mammography ± ultrasound ± MRI)
3. Histopathology/cytology (FNAC, core needle biopsy, or excision biopsy)

• Ultrasound preferred in: women <35 years (dense breast tissue), pregnant/lactating women, assessment of cystic vs. solid lesion, guidance for FNAC/biopsy, evaluation of axillary nodes
• Mammography preferred in: women >35-40 years, screening programme, detecting microcalcifications (DCIS)
• MRI preferred in: BRCA carriers (screening), assessing extent of lobular carcinoma (multifocality), implant assessment, post-lumpectomy margin re-evaluation, monitoring response to NACT, occult primary with axillary metastasis, pre-operative planning for BCS

• FNAC: Rapid, outpatient, gives cytology only (no architecture). Cannot distinguish invasive from in situ. False negative 5-10%.
• CNB (Tru-cut/core): Preferred - gives histology with tissue architecture, determines ER/PR/HER2, grade, lymphovascular invasion, Ki-67. Guides NACT and surgical planning.
• Vacuum-assisted biopsy (VAB): For microcalcifications/small lesions under stereotactic guidance.

• Early breast cancer (T1/T2, N0/N1): Only if symptomatic - CXR, LFTs, serum ALP
• Locally advanced breast cancer (T3/T4 or N2/N3):
  • Contrast-enhanced CT chest/abdomen/pelvis
  • Isotope bone scan (Tc99m bone scan)
  • PET-CT with 18F-FDG (alternative/complementary)
  • Serum ALP, LFTs, calcium
• Blood tests: CBC, LFT, RFT, Ca2+, tumour markers (CA 15-3, CEA - not for diagnosis, for monitoring)

• ER (Oestrogen receptor): Allred score or H-score; ≥1% positivity = ER+. Guides hormonal therapy
• PR (Progesterone receptor): ≥1% positivity = PR+
• HER2/neu: IHC 3+ (strong complete membrane staining >10% cells) = HER2+; IHC 2+ → FISH/CISH for amplification
• Ki-67: Proliferation index. <14% = low, 14-20% = intermediate, >20% = high
• Molecular subtypes:
  • Luminal A: ER+/PR+, HER2-, Ki-67 low (<14%) - best prognosis
  • Luminal B: ER+/PR+, HER2- with Ki67 high, OR HER2+
  • HER2-enriched: ER-/PR-, HER2+ - aggressive
  • Triple negative (TNBC): ER-/PR-/HER2- - worst prognosis, no targeted therapy

SECTION 4: STAGING - VIVA QUESTIONS

• cN0: No regional LN metastasis
• cN1: Mobile ipsilateral Level I/II axillary LN
• cN2a: Fixed/matted ipsilateral Level I/II axillary LN; cN2b: Internal mammary LN (without axillary)
• cN3a: Ipsilateral Level III (infraclavicular) LN; cN3b: Internal mammary + axillary; cN3c: Supraclavicular LN

• Stage 0: Tis N0 M0 (DCIS)
• Stage I: T1 N0 M0 (IA) / T0-1 N1mi M0 (IB)
• Stage IIA: T0-1 N1 M0; T2 N0 M0
• Stage IIB: T2 N1 M0; T3 N0 M0
• Stage IIIA: T0-2 N2; T3 N1-2
• Stage IIIB: T4 any N M0
• Stage IIIC: Any T N3 M0
• Stage IV: Any T, Any N, M1

• LCIS is removed - now classified as a benign high-risk lesion, NOT cancer
• Multiple synchronous tumours - use (m) modifier, classified by largest tumour
• Prefix (y) denotes post-neoadjuvant therapy pathologic staging
• Biological factors (ER, PR, HER2, grade, Oncotype DX) now incorporated for Prognostic Stage Groups (separate from Anatomical stage groups)
• Pathological complete response (pCR) after NACT downstages to ypN0

SECTION 5: HISTOPATHOLOGY - VIVA QUESTIONS

1. Paget's disease of nipple - chronic eczematous nipple eruption; pathognomonic Paget cells (large, pale, vacuolated) in rete pegs; associated with underlying DCIS ± invasive cancer
2. Invasive ductal carcinoma NST (no special type/scirrhous/simplex) - 80%, worst prognosis among special types
3. Medullary carcinoma - 4%, large cells, pushing margins, lymphocytic infiltrate; better prognosis despite high grade
4. Mucinous (colloid) carcinoma - 2%, mucin pools, best prognosis
5. Papillary carcinoma - 2%
6. Tubular carcinoma - 2%, excellent prognosis
7. Invasive lobular carcinoma - 10%, single file ("Indian file") pattern, multifocal/bilateral tendency, signet ring cells
8. Rare: Adenoid cystic, squamous cell, apocrine

1. Tubule formation (>75% = 1; 10-75% = 2; <10% = 3)
2. Nuclear pleomorphism (mild = 1; moderate = 2; severe = 3)
3. Mitotic count (per 10 HPF; threshold depends on microscope field area)

• Score 3-5: Grade 1 (well differentiated) - best prognosis
• Score 6-7: Grade 2 (moderately differentiated)
• Score 8-9: Grade 3 (poorly differentiated) - worst prognosis

• Presents as chronic, eczematous eruption of nipple - can be subtle or progress to ulcerated, weeping lesion
• Nearly always associated with extensive DCIS, may have underlying invasive cancer
• Biopsy: Paget cells - large, pale, vacuolated cells in rete pegs of epithelium (pathognomonic)
• Must differentiate from superficial spreading melanoma - Paget's: CEA+, S100-; Melanoma: S100+, CEA-
• Treatment: Lumpectomy (if nipple-areola complex uninvolved and no invasive component) or mastectomy

• Ductal carcinoma in situ: Malignant ductal epithelial cells confined within the basement membrane - no stromal invasion
• Detected on mammography as microcalcifications (comedo type - central necrosis with calcification)
• Van Nuys Prognostic Index guides treatment (size, margins, grade, age)
• Treatment: BCS with minimum 2 mm margins (unlike invasive cancer where "no ink on tumour" is sufficient) + radiation, OR mastectomy for extensive DCIS/diffuse microcalcifications
• LCIS: Now classified as high-risk benign lesion (not staged as cancer in AJCC 8th ed.) - managed with surveillance/risk reduction

SECTION 6: SURGICAL MANAGEMENT - VIVA QUESTIONS

• T1, T2 tumours (≤5 cm) with favourable tumour-to-breast ratio
• Unifocal disease
• Patient preference with access to radiotherapy

• Large tumour relative to breast size (poor cosmesis)
• Multicentric/multifocal disease in different quadrants
• Diffuse malignant microcalcifications (mammographic)
• Prior radiation to breast/chest wall
• Pregnancy (first/second trimester - radiation contraindicated)
• BRCA1/2 mutation (relative - high risk of ipsilateral recurrence)
• Persistent positive margins despite re-excision
• Patient preference/inability to attend radiotherapy

• Large tumours relative to breast size (tumour-to-breast ratio unfavourable)
• Multicentric disease
• Diffuse microcalcification (DCIS)
• BRCA1/2 mutation carriers
• Local recurrence after previous BCS
• Patient's choice
• Inability to receive radiotherapy

• Simple (total) mastectomy: Removal of breast only - no axillary clearance. For DCIS, prophylactic, palliative
• Modified radical mastectomy (MRM / Patey's): Breast + Level I/II/III axillary nodes; pectoralis major preserved, pectoralis minor removed/divided
• Halsted radical mastectomy: Breast + both pectoral muscles + axillary nodes - now historical, only for pectoral muscle invasion
• Skin-sparing mastectomy: Removes breast + NAC, preserves skin envelope for immediate reconstruction
• Nipple-sparing mastectomy (NSM): Preserves skin envelope + NAC; for prophylactic/early cancer without NAC involvement

• Level I (low axilla): Lateral to lateral border of pectoralis minor - pectoral (anterior), subscapular (posterior), lateral axillary nodes
• Level II (mid axilla): Behind pectoralis minor - central axillary nodes, interpectoral (Rotter's) nodes
• Level III (apical/infraclavicular): Medial to medial border of pectoralis minor - apical axillary nodes; drain into subclavian vein

• The sentinel node is the first node(s) draining the primary tumour in the axilla - concept: if SLN is negative, remaining nodes are almost certainly negative
• Technique: Dual technique - radiolabelled colloid (Tc99m) injected peri-tumorally the day before + blue dye (Patent blue/isosulphan blue) injected at surgery. Node detected by blue staining + gamma probe (>10x background = hot node)
• Single agent: Superparamagnetic iron oxide (SPIO/Magtrace) - newer magnetic tracer, no radiation
• Indications: Clinically and radiologically node-negative (cN0) early breast cancer
• If SLN negative: No further axillary surgery required
• If SLN positive (1-2 micrometastases/macrometastases): ACOSOG Z0011 trial - no ALND if undergoing BCS + tangential radiation + systemic therapy (for 1-2 positive SLNs)
• If SLN positive (>2 nodes, mastectomy, no radiation): Proceed to completion ALND

• Lymphoedema (most significant): 10-20% after ALND vs. <5% after SLNB. Risk factors: obesity, radiotherapy, infection
• Seroma formation: Most common early complication; requires repeated aspiration
• Wound infection
• Nerve injuries:
  • Intercostobrachial nerve (T2 lateral cutaneous): Medial arm/axilla numbness - commonly sacrificed
  • Long thoracic nerve of Bell (C5,6,7): Serratus anterior - winging of scapula
  • Thoracodorsal nerve (C6,7,8): Latissimus dorsi - weak shoulder extension/internal rotation
  • Medial pectoral nerve: pectoralis minor
• Shoulder stiffness and restricted abduction
• Axillary vein thrombosis (rare)

SECTION 7: NEOADJUVANT & SYSTEMIC THERAPY - VIVA QUESTIONS

• Locally advanced breast cancer (LABC): T3/T4, N2/N3 - to downstage for operability or BCS
• HER2+ or triple-negative breast cancer: NAST preferred even for operable tumours (high response rates, pathological CR guides further therapy)
• To assess in vivo chemosensitivity
• To allow time for genetic testing/decision making
• Converting inoperable to operable disease

• pCR = no residual invasive cancer in breast AND axillary nodes after NACT (ypT0/is ypN0)
• Surrogate endpoint for long-term survival - especially in HER2+ and TNBC
• TNBC: pCR ~40-60%; HER2+ with dual anti-HER2 therapy: pCR ~50-70%
• Non-pCR in TNBC: Can add capecitabine (CREATE-X trial)
• Non-pCR in HER2+: Switch to T-DM1 (trastuzumab emtansine) - KATHERINE trial

• Complete Response (CR): Lesion not detectable on clinical palpation + imaging
• Partial Response (PR): ≥30% reduction in maximal diameter
• Stable Disease (SD): <30% reduction in maximal diameter
• Progressive Disease (PD): ≥20% increase in maximal diameter

• AC (Adriamycin/doxorubicin + cyclophosphamide) x4 cycles → Paclitaxel/Docetaxel x4 cycles (sequential anthracycline-taxane regimen) - most common
• TC (Docetaxel + Cyclophosphamide) x4 - used when anthracycline contraindicated
• FEC (Fluorouracil + Epirubicin + Cyclophosphamide) → Docetaxel
• Dose-dense AC-T (every 2 weeks with G-CSF support): Better DFS in node-positive disease
• HER2+ targeted: Add Trastuzumab (Herceptin) ± Pertuzumab (dual anti-HER2 blockade, NEOSPHERE trial) to taxane regimen
• TNBC: Pembrolizumab (immune checkpoint inhibitor) + chemotherapy (KEYNOTE-522 trial) in high-risk TNBC

• Only for ER+ and/or PR+ tumours
• Pre-menopausal:
  • Tamoxifen (SERM - selective oestrogen receptor modulator) 20 mg/day x5 years (or 10 years in high-risk)
  • • Ovarian suppression (GnRH agonist: Goserelin/Leuprolide) in high-risk premenopausal
  • After ovarian suppression: Can switch to Aromatase Inhibitor (AI)
• Post-menopausal:
  • Aromatase Inhibitors (AIs): Anastrozole, Letrozole, Exemestane - superior to tamoxifen for DFS in post-menopausal women
  • Extended AI therapy up to 10 years in high-risk
• CDK4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) + AI: Standard for metastatic ER+/HER2- disease; Abemaciclib also adjuvant for high-risk early BC (monarchE trial)

• Humanized monoclonal antibody against HER2 (ErbB2) extracellular domain
• Mechanism: Blocks HER2 dimerisation, ADCC, receptor downregulation
• Indications: Adjuvant (1 year) in all HER2+ early breast cancer; neoadjuvant; metastatic
• Key toxicity: Cardiotoxicity - reversible left ventricular dysfunction/CHF (especially with anthracyclines - avoid concurrent use). Monitor LVEF at baseline and every 3 months
• Other: Infusion reactions (first dose), pulmonary toxicity (rare)
• Pertuzumab: Second anti-HER2 monoclonal antibody (blocks dimerisation domain) - combined with trastuzumab for neoadjuvant and metastatic settings (CLEOPATRA trial)
• T-DM1 (Trastuzumab emtansine/Kadcyla): Antibody-drug conjugate for residual disease post-NACT (KATHERINE trial)

SECTION 8: RADIOTHERAPY - VIVA QUESTIONS

• After BCS (breast conserving surgery): Always indicated to reduce local recurrence risk (reduces LR from ~25-30% to ~8-10%)
• After mastectomy (post-mastectomy radiotherapy - PMRT):
  • T3/T4 tumours
  • ≥4 positive axillary nodes (absolute indication)
  • 1-3 positive nodes in high-risk patients (young age, Grade 3, lymphovascular invasion, close margins)
  • Involved/close resection margins
• Boost dose: To tumour bed after whole-breast radiation in BCS (reduces local recurrence further)
• Regional nodal irradiation: Supraclavicular ± internal mammary nodes in high-risk

SECTION 9: LOCALLY ADVANCED & SPECIAL SITUATIONS - VIVA QUESTIONS

• Stage III disease: T3/T4 (any N, M0) or N2/N3 (any T, M0); or inoperable by clinical criteria
• Includes: Large primary (>5 cm), skin/chest wall involvement, fixed axillary nodes, supraclavicular nodes, inflammatory carcinoma
• Management (multimodal):
  1. NAST (neoadjuvant chemotherapy ± targeted therapy) to downstage
  2. Re-evaluate with triple assessment after NACT
  3. Surgery (mastectomy ± BCS if downstaged sufficiently)
  4. Post-operative radiotherapy (always indicated in LABC)
  5. Adjuvant systemic therapy (hormone/targeted as appropriate)

• T4d: Rapid onset of erythema + oedema (peau d'orange) involving ≥1/3 of breast skin - may or may not have palpable mass
• Pathology: Tumour emboli in dermal lymphatics (NOT inflammatory cells - hence "inflammatory" is a misnomer)
• Must be distinguished from: Breast abscess, mastitis, locally advanced cancer with skin oedema
• Worst prognosis of all breast cancer subtypes
• Management: NAST first (surgery first is NOT appropriate); then surgery (mastectomy - BCS not indicated); then PMRT
• Never do BCS in inflammatory breast cancer

• Additional points: Paget disease is considered a malignant condition of the nipple skin - must NOT be confused with Paget's disease of bone
• Mammography ± MRI mandatory to assess extent of underlying DCIS/invasive component
• If no palpable mass + limited NAC involvement: Central lumpectomy (excision of NAC + underlying tissue) + radiotherapy
• If extensive DCIS or invasive cancer: Mastectomy

SECTION 10: PROGNOSIS & MOLECULAR MARKERS - VIVA QUESTIONS

• Nodal status: Single most important prognostic factor
• Tumour size
• Histological/nuclear grade (Nottingham grade)
• Lymphovascular invasion
• Hormone receptor status (ER/PR positivity = better prognosis)
• HER2 overexpression (worse prognosis but targetable)
• Ki-67 (proliferation index)
• DNA ploidy, S-phase fraction
• Extent of intraductal component

• Age, menopausal status, family history, immunosuppression

• RT-PCR based 21-gene assay on paraffin-embedded tumour tissue
• Generates a Recurrence Score (RS) 0-100 for ER+/HER2- node-negative (and some node-positive) patients
• Low RS (0-10): Low recurrence risk; endocrine therapy alone; chemotherapy NOT beneficial
• Intermediate RS (11-25): TAILORx trial showed endocrine therapy alone non-inferior to chemo + endocrine (especially in patients <50 years, some benefit from chemo)
• High RS (>25): High recurrence risk; chemotherapy + endocrine therapy recommended
• Clinically: Avoids unnecessary chemotherapy in low-risk ER+ patients

• 70-gene expression profile FDA-approved for Stage I/II node-negative ER+/- breast cancers
• Classifies into Low or High genomic risk
• MINDACT trial: Patients with high clinical risk but low genomic risk - 94.7% survival without distant metastasis at 5 years without chemotherapy (met non-inferiority endpoint)
• Can be used to guide chemotherapy decision in "genomically low-risk" patients despite high clinical risk

SECTION 11: SCREENING - VIVA QUESTIONS

• Mammographic screening: Every 2 years for women aged 50-69 years (NHS/IARC); ACS recommends annual mammography from age 45-54, biennial from 55
• BRCA1/2 or high-risk families: Annual MRI + mammogram from age 30 (or 10 years before youngest affected relative)
• Breast self-examination (BSE): No longer universally recommended (no mortality benefit in trials) but breast awareness promoted
• Digital breast tomosynthesis (3D mammography): Improved sensitivity in dense breasts

SECTION 12: SUPERSPECIALITY LEVEL QUESTIONS

• Randomised trial: T1/T2 breast cancer, 1-2 positive SLNs, undergoing BCS + whole-breast tangential radiation + systemic therapy
• Randomised to completion ALND vs. no ALND
• Result: No difference in overall survival or locoregional recurrence at 10 years
• Impact: Eliminated routine ALND for 1-2 positive SLNs in BCS patients receiving whole-breast radiation - dramatically reduced lymphoedema

• In cN1 patients downstaged to ycN0 after NACT: SLNB is feasible but has higher false-negative rate
• SENTINA and SN FNAC trials: False negative rate ~14% with single-agent technique, but <10% with dual-agent technique + retrieval of ≥3 SLNs + IHC
• Current practice: Dual-agent SLNB with ≥3 nodes retrieved; tattooed/clipped positive node must be excised (targeted axillary dissection - TAD)
• TAD (Targeted Axillary Dissection): Clip placed in biopsy-proven positive axillary node before NACT → post-NACT, remove clipped node + SLNs → very low false-negative rate

• TNBC or HER2- patients with residual invasive disease after NACT and surgery
• Randomised to Capecitabine x8 cycles vs. observation
• Result: Significant improvement in DFS and OS with capecitabine (especially TNBC subgroup)
• Now standard of care: Adjuvant capecitabine for TNBC with non-pCR after NACT

• HER2+ patients with residual disease after neoadjuvant trastuzumab-based chemotherapy
• Randomised to adjuvant T-DM1 (trastuzumab emtansine) vs. trastuzumab
• Result: T-DM1 significantly improved invasive DFS (88.3% vs. 77% at 3 years); 50% reduction in recurrence risk
• Now standard: T-DM1 for HER2+ residual disease after NACT

• Tumour suppressor genes; involved in DNA double-strand break repair (homologous recombination)
• BRCA1: Chromosome 17q; lifetime breast cancer risk ~57-72%; also ovarian cancer (~44%)
• BRCA2: Chromosome 13q; lifetime breast cancer risk ~40-84%; male breast cancer risk elevated
• Indications for genetic testing: Triple-negative <60 years, bilateral/multifocal, age <35, male breast cancer, Ashkenazi Jewish heritage, strong family history (2+ first/second-degree relatives with breast/ovarian cancer)
• Management of BRCA carriers:
  • Enhanced surveillance: Annual MRI from age 25, mammography from 30
  • Chemoprevention: Tamoxifen (pre-menopausal), AIs (post-menopausal) - ~40% risk reduction
  • Risk-reducing surgery: Bilateral risk-reducing mastectomy (~95% risk reduction), Bilateral salpingo-oophorectomy (BSO by age 35-40 in BRCA1; 40-45 in BRCA2) - reduces breast cancer risk by ~50% and ovarian cancer risk by ~95%

• PARP (poly ADP-ribose polymerase) inhibitors: Olaparib, Niraparib, Talazoparib
• Mechanism: Synthetic lethality - BRCA-mutated cells already deficient in homologous recombination; PARP inhibition blocks base excision repair → double-strand breaks → cell death
• Indications: Germline BRCA1/2 mutation, HER2-negative metastatic breast cancer (OlympiAD trial: Olaparib vs. chemotherapy - superior PFS)
• Adjuvant: OlympiA trial - adjuvant Olaparib in high-risk germline BRCA-mutated HER2- early breast cancer with residual disease or high-risk node-positive disease - improved DFS and OS

• CDK4/6 (cyclin-dependent kinase 4/6) drive G1-S phase cell cycle progression
• Inhibitors: Palbociclib, Ribociclib, Abemaciclib
• Indication: ER+/HER2- metastatic breast cancer + AI or fulvestrant - became standard of care (PALOMA-2, MONALEESA-2, MONARCH-2 trials)
• Adjuvant abemaciclib (monarchE trial): High-risk ER+/HER2- early breast cancer (≥4 positive nodes, OR 1-3 nodes with Grade 3/tumour ≥5cm/Ki-67 ≥20%) - significant improvement in iDFS

• International Society of Lymphology (ISL) staging:
  • Stage 0: Latent - no oedema but impaired lymph transport
  • Stage I: Reversible - pitting oedema, reduces with elevation
  • Stage II: Irreversible - non-pitting, fibrosis, does not reduce with elevation
  • Stage III: Lymphostatic elephantiasis - gross deformity, skin changes (hyperkeratosis, papillomatosis)
• Management: Complex decongestive therapy (CDT) - manual lymphatic drainage (MLD) + compression bandaging + remedial exercises + skin care; then maintenance compression garments. Surgery (VLNT - vascularised lymph node transfer, lymphaticovenous anastomosis - LVA) for refractory cases.

SECTION 13: VIVA ON CLINICAL FINDINGS INTEGRATION

• Clinical staging: T2 (>2-5 cm) N1 (movable ipsilateral axillary nodes) M0 = Stage IIA-IIB
• Triple assessment: Clinical + mammogram ± USG + CNB with IHC
• Staging CT + bone scan (T2N1 - may be done to confirm M0)
• Based on IHC: Molecular subtype guides systemic therapy
• Surgery: MRM (mastectomy + Level I/II ALND) OR BCS (WLE + SLNB/ALND if SLNB+) depending on tumour-to-breast ratio and patient preference
• Adjuvant: Chemotherapy (AC-T regimen), ± trastuzumab (if HER2+), ± endocrine (if ER+), + radiotherapy (post-BCS always; post-mastectomy if ≥4 nodes or other risk factors)

• TNBC (ER-/PR-/HER2-): No hormonal or anti-HER2 therapy
• Preferred approach: Neoadjuvant chemotherapy first (AC-T ± pembrolizumab if PD-L1 positive/high-risk - KEYNOTE-522)
• Assess response with RECIST
• If pCR: Surgery (BCS or mastectomy) + radiation; consider adjuvant pembrolizumab
• If residual disease (non-pCR): Surgery + adjuvant capecitabine (CREATE-X)
• Test for germline BRCA mutation - if positive: PARP inhibitor option
• Poor prognosis overall; high risk of visceral/CNS metastasis

• Bone (most common - 70%): Osteolytic lesions; spine, pelvis, femur, ribs. Presents with bone pain, pathological fracture, hypercalcaemia, spinal cord compression. Diagnosed with bone scan/CT/MRI.
• Lung/pleura: Cough, dyspnoea, haemoptysis, pleural effusion
• Liver: Hepatomegaly, jaundice, raised LFTs, ascites
• Brain/CNS (especially HER2+ and TNBC): Headache, seizures, focal neurological deficit, visual disturbances. Managed with whole-brain radiotherapy ± SRS ± targeted CNS-penetrant drugs (lapatinib, tucatinib, neratinib)
• Adrenal, ovary, peritoneum: Especially lobular carcinoma (predilection for unusual sites)

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