Clinical Assessment: 35M with Postprandial Spasmodic Abdominal Pain + Deranged LFTs

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pres.title = "Breast Cancer: Anatomy, Clinical Examination & Treatment";

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  s.addNotes("Welcome everyone. This lecture covers the complete spectrum of breast cancer for MBBS final year students – from anatomy and physiology of the breast, through clinical examination techniques, to staging and modern treatment principles. The session is designed to last approximately 60-75 minutes.");
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// ─── BUILD SLIDES ────────────────────────────────────────────────────────────

// SLIDE 1: Title
titleSlide();

// SLIDE 2: Learning Objectives
contentSlide(
  "Learning Objectives",
  [
    "Describe the anatomy of the breast including its blood supply, lymphatic drainage, and nerve supply",
    "Understand the hormonal changes and cyclical breast changes across a woman's lifetime",
    "List the risk factors and epidemiology of breast cancer",
    "Perform a systematic clinical breast examination (CBE)",
    "Apply the Triple Assessment approach for breast evaluation",
    "Classify breast carcinomas by histological type and molecular subtype",
    "Describe TNM staging and the overall management principles of breast cancer",
    "Explain surgical, systemic and radiation treatment options",
    "Counsel patients on breast cancer screening and prevention",
  ],
  "Read these objectives at the start of the lecture. Let students know this is an exam-relevant topic – clinical breast examination is a standard OSCE station, and staging/treatment is commonly tested in written papers."
);

// SLIDE 3: Epidemiology
contentSlide(
  "Epidemiology of Breast Cancer",
  [
    { text: "Global Burden", bold: true, sub: [
      "Most common cancer in women worldwide – 2.3 million new cases per year (WHO 2020)",
      "Second leading cause of cancer death in women",
      "1 in 8 women will develop breast cancer in their lifetime",
    ]},
    { text: "Regional Data", bold: true, sub: [
      "Higher incidence in Western countries (US, UK, Australia)",
      "Rapidly rising incidence in South Asia due to lifestyle changes",
      "India: ~178,000 new cases/year; median age at diagnosis ~50 years (younger than West)",
    ]},
    { text: "Male Breast Cancer", bold: true, sub: [
      "< 1% of all breast cancers",
      "Associated with BRCA2 mutation, Klinefelter syndrome, excess estrogen",
    ]},
    { text: "Survival", bold: true, sub: [
      "5-year survival: Stage I = 99%, Stage II = 86%, Stage III = 57%, Stage IV = 29%",
      "Early detection is the single most important prognostic factor",
    ]},
  ],
  "Emphasize that breast cancer is the MOST common cancer in Indian women, now surpassing cervical cancer in urban areas. The younger age at presentation (40s-50s vs 60s in the West) is an important epidemiological difference."
);

// SLIDE 4: SECTION – Anatomy
sectionDivider("SECTION 1", "Anatomy of the Breast");

// SLIDE 5: Gross Anatomy
contentSlide(
  "Anatomy of the Breast – Gross Structure",
  [
    { text: "Location & Extent", bold: true, sub: [
      "Lies on the anterior chest wall, overlying pectoralis major and serratus anterior",
      "Vertical: 2nd to 6th rib | Horizontal: Lateral sternal border to mid-axillary line",
      "Axillary tail of Spence extends into axilla through opening in deep fascia (Foramen of Langer)",
    ]},
    { text: "Internal Structure", bold: true, sub: [
      "15–20 lobes arranged radially around the nipple-areola complex (NAC)",
      "Each lobe → lobules → terminal duct lobular unit (TDLU) – site of most breast cancers",
      "Cooper's ligaments: fibrous septa connecting skin to deep fascia; invasion causes skin dimpling",
      "Retromammary space: layer of loose areolar tissue between breast and pectoralis fascia",
    ]},
    { text: "Nipple & Areola", bold: true, sub: [
      "Nipple contains 15–20 lactiferous duct openings",
      "Areola contains Montgomery's glands (modified sebaceous glands)",
    ]},
  ],
  "Draw or show the breast quadrant diagram on the board. Emphasize the axillary tail – cancer there can be mistaken for an axillary lymph node. Cooper's ligaments: when invaded by tumor, they shorten and cause the classic 'skin dimpling/peau d'orange' sign."
);

// SLIDE 6: Blood Supply & Lymphatics
twoColSlide(
  "Blood Supply & Lymphatic Drainage",
  "Blood Supply",
  [
    "Medial: Internal mammary (thoracic) artery – 60% of supply",
    "Lateral: Lateral thoracic artery (branch of axillary artery)",
    "Intercostal perforators (2nd–5th)",
    "Superior: Thoracoacromial artery",
    "Venous drainage: Internal mammary veins → Batson's plexus (route for vertebral metastases)",
  ],
  "Lymphatic Drainage (Clinically Critical)",
  [
    "Axillary nodes: 75% of lymphatic drainage – MOST IMPORTANT",
    "Level I (anterior/lateral) → Level II (central) → Level III (apical) nodes",
    "Internal mammary nodes: medial breast tumors",
    "Supraclavicular nodes: advanced disease (N3)",
    "Cross-drainage to opposite breast (explains contralateral spread)",
    "Sentinel node biopsy: first node to receive drainage from tumor",
  ],
  "The axillary node levels (I, II, III) are defined by their relationship to pectoralis minor. Exam tip: Ask 'Which quadrant is most likely to develop breast cancer?' Answer: Upper outer quadrant (UOQ) – 50% of cancers, because it has the most glandular tissue and is closest to the axilla."
);

// SLIDE 7: Nerve Supply & Quadrants
twoColSlide(
  "Nerve Supply & Breast Quadrants",
  "Nerve Supply",
  [
    "Supraclavicular nerve (C3, C4): upper skin",
    "Lateral cutaneous branches of intercostals (T4–T6): lateral skin and nipple",
    "Medial cutaneous branches of intercostals (T2–T6): medial skin",
    "Long thoracic nerve (C5–C7): serratus anterior – injury → winged scapula",
    "Thoracodorsal nerve (C6–C8): latissimus dorsi – injury → weak shoulder extension",
    "Intercostal brachial nerve: sensation inner arm – often cut during axillary dissection",
  ],
  "Breast Quadrants & Cancer Distribution",
  [
    "Upper Outer Quadrant (UOQ): 50% – most common",
    "Upper Inner Quadrant (UIQ): 15%",
    "Lower Outer Quadrant (LOQ): 10%",
    "Lower Inner Quadrant (LIQ): 5%",
    "Central (subareolar): 17%",
    "Axillary tail: 3%",
  ],
  "The nerve supply is essential for surgical anatomy. During axillary clearance, three nerves are at risk: long thoracic (winged scapula), thoracodorsal (weak shoulder abduction), and intercostal brachial (inner arm numbness). Students are frequently asked about these in viva and OSCE."
);

// SLIDE 8: Hormonal Changes
contentSlide(
  "Hormonal Changes & Breast Physiology Across Life",
  [
    { text: "Puberty", bold: true, sub: [
      "Estrogen drives ductal elongation and branching",
      "Progesterone drives lobular development",
      "Breast development: Tanner stages I–V",
    ]},
    { text: "Menstrual Cycle", bold: true, sub: [
      "Follicular phase: estrogen stimulates epithelial proliferation",
      "Luteal phase: progesterone promotes secretory activity; breast feels lumpy and tender premenstrually",
      "CBE should ideally be performed on days 5–10 of cycle (least hormonal influence)",
    ]},
    { text: "Pregnancy & Lactation", bold: true, sub: [
      "Prolactin + HPL promote full lobular differentiation → milk secretion",
      "Breast nearly entirely replaced by lobules; stroma markedly reduced",
    ]},
    { text: "Menopause", bold: true, sub: [
      "Loss of estrogen → lobular involution, replacement by fat (fatty breast on mammogram)",
      "Post-menopausal HRT (combined estrogen + progesterone) → ↑ breast cancer risk",
    ]},
  ],
  "The timing of CBE relative to the menstrual cycle is frequently asked. The physiological lumpiness of the breast in the luteal phase can confuse both patients and clinicians. Advise patients to self-examine after their period ends."
);

// SLIDE 9: SECTION – Risk Factors
sectionDivider("SECTION 2", "Risk Factors & Pathogenesis");

// SLIDE 10: Risk Factors
twoColSlide(
  "Risk Factors for Breast Cancer",
  "Non-Modifiable Risk Factors",
  [
    "Female sex (99:1 ratio)",
    "Age: risk increases with age; peak 50–70 years",
    "BRCA1/BRCA2 gene mutations: lifetime risk 60–85%",
    "Strong family history (1st degree relative)",
    "Personal history of breast cancer",
    "Previous breast biopsy with atypical hyperplasia (4–5× risk)",
    "DCIS or LCIS (8–10× risk of invasive cancer)",
    "Early menarche (<12 yrs) / late menopause (>55 yrs)",
    "Nulliparity or first childbirth after age 30",
    "Dense breast tissue on mammography",
  ],
  "Modifiable Risk Factors",
  [
    "HRT (combined estrogen + progestogen) – ↑ risk",
    "Oral contraceptive pill – slight ↑ risk (returns to baseline on stopping)",
    "Obesity post-menopause (adipose tissue produces estrogen)",
    "Alcohol consumption (dose-dependent ↑ risk)",
    "Sedentary lifestyle / physical inactivity",
    "Radiation exposure (therapeutic radiation to chest in childhood/young adulthood)",
    "Night shift work – possible circadian disruption",
    "Breastfeeding is PROTECTIVE (↓ risk)",
    "Regular physical exercise is PROTECTIVE",
  ],
  "Mnemonic for risk factors: ABCDE – Age, BRCA, Cancer history (personal/family), Dense breast / DES exposure, Early menarche/Estrogen. The BRCA mutations are key: BRCA1 → basal-like triple-negative cancers; BRCA2 → luminal/ER+ cancers and male breast cancer."
);

// SLIDE 11: BRCA Genetics
contentSlide(
  "Hereditary Breast Cancer – BRCA1 & BRCA2",
  [
    { text: "Genetics", bold: true, sub: [
      "BRCA1: chromosome 17q21 – tumor suppressor gene (DNA repair – homologous recombination)",
      "BRCA2: chromosome 13q12–13 – DNA repair; also involved in ovarian and male breast cancer",
      "Autosomal dominant inheritance; lifetime breast cancer risk: BRCA1 = 72%, BRCA2 = 69%",
    ]},
    { text: "When to Suspect Hereditary Breast Cancer", bold: true, sub: [
      "Multiple first-degree relatives with breast or ovarian cancer",
      "Bilateral breast cancer or early onset (<40 years)",
      "Male breast cancer in family",
      "Associated ovarian, pancreatic, or prostate cancer",
      "Ashkenazi Jewish ancestry",
    ]},
    { text: "Management of BRCA Carriers", bold: true, sub: [
      "Annual MRI screening from age 25–30",
      "Annual mammography from age 30–70",
      "Risk-reducing bilateral mastectomy (↓ risk by 90–95%)",
      "Risk-reducing bilateral salpingo-oophorectomy (after childbearing completed)",
      "Chemoprevention: Tamoxifen or raloxifene",
    ]},
  ],
  "Discuss the landmark Angelina Jolie effect – public awareness increased BRCA testing requests. Emphasize genetic counseling before and after BRCA testing. Other susceptibility genes: TP53 (Li-Fraumeni), PTEN (Cowden syndrome), CDH1, PALB2, ATM, CHEK2."
);

// SLIDE 12: SECTION – Clinical Examination
sectionDivider("SECTION 3", "Clinical Breast Examination");

// SLIDE 13: Symptoms & History
contentSlide(
  "History Taking – Presenting Complaints",
  [
    { text: "Common Presenting Symptoms", bold: true, sub: [
      "Breast lump (most common) – note onset, size, change, tenderness",
      "Nipple discharge – character (serous, blood-stained, milky), unilateral vs bilateral",
      "Nipple change – inversion, eczema, retraction",
      "Breast pain (mastalgia) – cyclical vs non-cyclical",
      "Skin changes – redness, peau d'orange, dimpling, ulceration",
      "Axillary lump (lymphadenopathy)",
      "Systemic symptoms – bone pain (metastases), dyspnea, jaundice",
    ]},
    { text: "Relevant History", bold: true, sub: [
      "Menstrual and obstetric history (menarche, parity, breastfeeding, menopause)",
      "Hormone use (OCP, HRT)",
      "Personal and family history of breast/ovarian cancer",
      "Previous biopsies, radiation, surgeries",
      "Medications, alcohol, smoking",
    ]},
  ],
  "Blood-stained nipple discharge is a red flag – think intraductal papilloma (most common cause) or DCIS/malignancy. Bilateral milky discharge = galactorrhea → check prolactin. Cyclical mastalgia is almost always benign; non-cyclical mastalgia in an older woman warrants imaging."
);

// SLIDE 14: Clinical Examination – Inspection
contentSlide(
  "Clinical Breast Examination – Inspection",
  [
    { text: "Positions for Inspection", bold: true, sub: [
      "1. Sitting, arms at sides (resting)",
      "2. Sitting, arms raised above head (exposes lower breast, accentuates tethering)",
      "3. Sitting, hands pressed on hips (contracts pectoralis – reveals deep tethering)",
      "4. Sitting, leaning forward (pendulous breast – gravity reveals dimpling)",
    ]},
    { text: "What to Inspect", bold: true, sub: [
      "Size and symmetry (mild asymmetry is normal; new asymmetry is significant)",
      "Skin: erythema, peau d'orange (brawny edema due to dermal lymphatic obstruction), ulceration, satellite nodules",
      "Nipple: retraction, inversion, deviation, eczema (Paget's disease), discharge",
      "Visible veins: dilated veins → increased vascularity (pregnancy, large tumors)",
      "Scars from previous surgery",
    ]},
    { text: "Key Signs", bold: true, sub: [
      "Peau d'orange: skin thickening + dimpling resembling orange peel → lymphedema from tumor block",
      "Skin dimpling: Cooper's ligament involvement by tumor",
      "Nipple retraction: ductal involvement; if long-standing may be benign",
    ]},
  ],
  "Demonstrate these positions practically or show photographs. Peau d'orange is PATHOGNOMONIC of inflammatory carcinoma until proven otherwise. Paget's disease of nipple = eczema of nipple-areola with underlying DCIS or invasive cancer – always biopsy persistent nipple eczema."
);

// SLIDE 15: Clinical Examination – Palpation
contentSlide(
  "Clinical Breast Examination – Palpation",
  [
    { text: "Technique (Bailey & Love)", bold: true, sub: [
      "Patient supine, arm behind head (ipsilateral), small pillow under shoulder",
      "Use pads of THREE fingers (index, middle, ring), not fingertips",
      "CLOCK METHOD: concentric circles OR radial spokes from nipple outward",
      "Also palpate the axillary tail specifically",
      "Squeeze the nipple gently to elicit discharge",
    ]},
    { text: "Characterizing a Lump (7 Features)", bold: true, sub: [
      "1. Site and quadrant  2. Size (cm)  3. Shape (spherical/irregular)",
      "4. Surface (smooth/nodular)  5. Edge/margin (well-defined / ill-defined)",
      "6. Consistency (soft/firm/hard)  7. Mobility (freely mobile / tethered / fixed)",
    ]},
    { text: "Features Suggesting Malignancy", bold: true, sub: [
      "Hard, irregular, ill-defined lump; skin or chest wall fixation",
      "Axillary lymphadenopathy; skin changes (dimpling, peau d'orange)",
    ]},
  ],
  "Exam tip: 'Tethering' = movement restricted in ONE plane (Cooper's ligaments); 'Fixed' = immobile in ALL planes (chest wall invasion). Benign lump mnemonic: SMOOTH – Smooth, Mobile, Oval, Tender (often), Hormonal fluctuation, Young age. Malignant lump: HARD – Hard, Attached, Rough, Dimpling/Discharge."
);

// SLIDE 16: Axillary Examination
contentSlide(
  "Axillary & Supraclavicular Examination",
  [
    { text: "Axillary Examination", bold: true, sub: [
      "Support patient's arm with your ipsilateral hand (relaxes pectoralis and arm muscles)",
      "Palpate with the right hand for LEFT axilla and vice versa",
      "Examine all 5 groups: anterior (pectoral), posterior (subscapular), medial (central), lateral (brachial), apical",
      "Note: size, number, consistency, matting (fixed to each other), fixation to skin or chest wall",
    ]},
    { text: "Significance of Axillary Nodes", bold: true, sub: [
      "N0: No palpable nodes",
      "N1: Mobile ipsilateral axillary nodes (Level I/II)",
      "N2: Fixed or matted axillary nodes",
      "N3: Internal mammary or supraclavicular nodes",
    ]},
    { text: "Supraclavicular Examination", bold: true, sub: [
      "Palpate both fossae from behind the patient",
      "Supraclavicular nodes = N3 (Stage IIIC) – advanced disease",
    ]},
    { text: "Also Examine", bold: true, sub: [
      "Contralateral breast and axilla",
      "Abdomen for hepatomegaly (liver metastases), spine for tenderness",
    ]},
  ],
  "Matted fixed nodes = nodes clumped together, fixed to axillary contents or skin = N2 disease = Stage IIIA. This contrasts sharply with mobile N1 nodes. Virchow's node (left supraclavicular) being palpable in breast cancer is a sign of distant spread."
);

// SLIDE 17: Triple Assessment
contentSlide(
  "Triple Assessment – The Diagnostic Gold Standard",
  [
    { text: "Triple Assessment = Clinical + Imaging + Histology/Cytology", bold: true, sub: [
      "Combined diagnostic accuracy approaches 100% (Bailey and Love, 28th Ed.)",
      "Each component scored 1–5 (1 = normal, 5 = malignant)",
      "All three arms must be concordant; discordance → biopsy",
    ]},
    { text: "1. Clinical Examination (C1–C5)", bold: true, sub: [
      "C1: Normal | C2: Benign | C3: Uncertain | C4: Suspicious | C5: Malignant",
    ]},
    { text: "2. Imaging (U1–U5 / M1–M5)", bold: true, sub: [
      "Ultrasound (U1–U5): preferred in <40 years (dense breasts)",
      "Mammography (M1–M5): preferred in >40 years",
      "MRI: staging, implants, occult primary, post-treatment monitoring",
      "BI-RADS scoring: BI-RADS 4–5 → biopsy mandatory",
    ]},
    { text: "3. Tissue Sampling", bold: true, sub: [
      "Fine Needle Aspiration Cytology (FNAC): quick, cheap – gives cytology (no architecture)",
      "Core needle biopsy (Tru-cut): preferred – gives histology + receptor status (ER/PR/HER2)",
      "Excisional biopsy: if other methods inconclusive",
    ]},
  ],
  "The triple assessment is the exam model for breast diagnosis. Emphasize that FNAC only gives CYTOLOGY (no tissue architecture, cannot distinguish in situ from invasive); core needle biopsy gives HISTOLOGY and receptor status which is essential for treatment planning."
);

// SLIDE 18: Imaging – Mammography & USG
twoColSlide(
  "Breast Imaging – Mammography vs Ultrasound",
  "Mammography",
  [
    "Two views: craniocaudal (CC) and mediolateral oblique (MLO)",
    "Preferred in women >40 years",
    "Detects: microcalcifications (DCIS), spiculated mass, architectural distortion",
    "Sensitivity ~80–85%; reduced in dense breasts",
    "Screening: annual from age 40–74 (USA) / age 50–70 (UK)",
    "BI-RADS 0: Incomplete | 1: Normal | 2: Benign | 3: Probably benign (6-mo follow-up) | 4: Suspicious (biopsy) | 5: Highly malignant | 6: Known malignancy",
    "Radiation dose: ~1 mGy per film (very low)",
  ],
  "Ultrasound",
  [
    "Preferred in women <40 (dense breast tissue)",
    "Best to distinguish CYSTIC vs SOLID lesion",
    "Simple cyst: anechoic, smooth wall, posterior enhancement → benign, no biopsy needed",
    "Complex cyst: internal echoes / thick wall → biopsy",
    "Malignant features: hypoechoic, irregular margins, taller-than-wide, posterior shadowing",
    "Used to guide FNAC / core biopsy and sentinel node biopsy",
    "Axillary ultrasound: mandatory when cancer diagnosed",
  ],
  "Key exam scenario: 25-year-old with breast lump → start with ULTRASOUND. 55-year-old with breast lump → start with MAMMOGRAM. MRI is not first-line but is gold standard for extent of disease, lobular carcinoma staging, and BRCA carrier screening."
);

// SLIDE 19: SECTION – Pathology
sectionDivider("SECTION 4", "Pathology & Classification of Breast Cancer");

// SLIDE 20: Classification
contentSlide(
  "Histological Classification of Breast Cancer",
  [
    { text: "In Situ Carcinoma (non-invasive)", bold: true, sub: [
      "Ductal Carcinoma In Situ (DCIS): malignant cells confined to ducts; basement membrane intact",
      "DCIS grades: low (nuclear grade 1), intermediate (grade 2), high (grade 3 – comedo type)",
      "Lobular Carcinoma In Situ (LCIS): marker of increased bilateral breast cancer risk (not a true precursor)",
    ]},
    { text: "Invasive (Infiltrating) Carcinoma", bold: true, sub: [
      "Invasive Ductal Carcinoma (IDC / NST – No Special Type): ~75% of all breast cancers",
      "Invasive Lobular Carcinoma (ILC): ~15%; single-file 'Indian file' pattern; often ER+, multifocal",
      "Mucinous (colloid) carcinoma: older women, good prognosis",
      "Tubular carcinoma: well-differentiated, excellent prognosis",
      "Medullary carcinoma: high grade but paradoxically good prognosis (BRCA1-associated)",
      "Inflammatory carcinoma: diffuse dermal lymphatic invasion; worst prognosis; T4d",
    ]},
    { text: "Paget's Disease of the Nipple", bold: true, sub: [
      "Eczematoid nipple change with underlying DCIS or invasive cancer",
      "Paget cells (large clear cells) in epidermis of nipple",
    ]},
  ],
  "Robbins: IDC/NST is the most common type and arises from TDLU. ILC has a diffuse 'Indian file' infiltration pattern which makes it difficult to palpate and has a higher rate of bilaterality and multifocality. Inflammatory carcinoma is NOT a histologic type – it is a clinical stage (T4d)."
);

// SLIDE 21: Molecular Subtypes
tableSlide(
  "Molecular Subtypes of Breast Cancer (Intrinsic Subtypes)",
  ["Subtype", "ER", "PR", "HER2", "Ki-67", "% Cases", "Prognosis / Notes"],
  [
    ["Luminal A", "+", "+", "–", "Low (<14%)", "40–50%", "Best prognosis; hormone sensitive"],
    ["Luminal B (HER2–)", "+", "+/–", "–", "High (≥14%)", "20%", "Intermediate; chemo often needed"],
    ["Luminal B (HER2+)", "+", "+/–", "+", "Any", "10%", "Anti-HER2 + hormone therapy"],
    ["HER2-enriched", "–", "–", "+", "High", "15%", "Aggressive; anti-HER2 therapy"],
    ["Triple Negative (TNBC)", "–", "–", "–", "High", "15%", "Worst prognosis; BRCA1-assoc.; chemo only"],
  ],
  "Molecular subtypes guide treatment – this table is ESSENTIAL for students to memorize. Luminal A: tamoxifen/aromatase inhibitors only, often no chemo. TNBC: chemo is the only systemic option (no hormone or anti-HER2 receptors). HER2-enriched: trastuzumab (Herceptin) is transformative. PAM50 gene assay can formally classify subtypes."
);

// SLIDE 22: Grading & Staging Header
sectionDivider("SECTION 5", "Grading, Staging & Prognostic Factors");

// SLIDE 23: Nottingham Grading
contentSlide(
  "Histological Grading – Nottingham (Elston-Ellis) System",
  [
    { text: "Three Features Scored 1–3 Each:", bold: true, sub: [
      "1. Tubule / gland formation: >75% = 1 | 10–75% = 2 | <10% = 3",
      "2. Nuclear pleomorphism: small/regular = 1 | moderate = 2 | marked variation = 3",
      "3. Mitotic count: per 10 high-power fields (HPF) – scored 1–3 based on microscope calibration",
    ]},
    { text: "Total Score & Grade:", bold: true, sub: [
      "Score 3–5 → Grade 1 (Well differentiated) – Good prognosis",
      "Score 6–7 → Grade 2 (Moderately differentiated) – Intermediate",
      "Score 8–9 → Grade 3 (Poorly differentiated) – Poor prognosis",
    ]},
    { text: "Prognostic Significance", bold: true, sub: [
      "Grade correlates with 10-year survival: Grade 1 = 85%, Grade 2 = 60%, Grade 3 = 45%",
      "High grade + lymph node metastases = most powerful adverse prognostic combination",
    ]},
  ],
  "The Nottingham system replaces the older Scarff-Bloom-Richardson system. Emphasize that grade is NOT the same as stage. Grade = intrinsic tumor aggressiveness (histology); Stage = extent of disease spread (clinical/pathological). Both are independently prognostic."
);

// SLIDE 24: TNM Staging Table
tableSlide(
  "TNM Staging of Breast Cancer (AJCC 8th Edition)",
  ["Component", "Category", "Description"],
  [
    ["T (Tumor)", "Tis", "Carcinoma in situ (DCIS/LCIS/Paget's)"],
    ["", "T1 (a/b/c)", "≤20 mm"],
    ["", "T2", "20–50 mm"],
    ["", "T3", ">50 mm"],
    ["", "T4 (a/b/c/d)", "Chest wall or skin involvement; T4d = inflammatory"],
    ["N (Nodes)", "N0", "No regional node metastasis"],
    ["", "N1", "Mobile ipsilateral axillary nodes (I/II)"],
    ["", "N2", "Fixed/matted axillary OR internal mammary nodes"],
    ["", "N3", "Infraclavicular, supraclavicular, or large IMN involvement"],
    ["M (Metastasis)", "M0", "No distant metastasis"],
    ["", "M1", "Distant metastasis (bone, lung, liver, brain)"],
  ],
  "AJCC 8th edition (2017) introduced 'prognostic stage groups' that incorporate biologic factors (ER/PR/HER2/grade) in addition to anatomical TNM. Common exam question: 'A patient with T2N1M0 breast cancer – what stage?' Answer: Stage IIA-IIB depending on N. T4 = always at least Stage IIIB."
);

// SLIDE 25: Staging Groups
tableSlide(
  "Breast Cancer Stage Grouping & Survival",
  ["Stage", "TNM", "5-Year Survival (Approx.)", "Notes"],
  [
    ["Stage 0", "Tis N0 M0", "~99%", "DCIS / LCIS – non-invasive"],
    ["Stage I (IA/IB)", "T1 N0 M0", "~99%", "Small tumor, node-negative"],
    ["Stage IIA", "T0-1 N1 M0 / T2 N0 M0", "~93%", "Early disease"],
    ["Stage IIB", "T2 N1 M0 / T3 N0 M0", "~75%", "Intermediate"],
    ["Stage IIIA", "T0-3 N2 M0 / T3 N1 M0", "~66%", "Locally advanced"],
    ["Stage IIIB", "T4 N0-2 M0", "~57%", "Skin/chest wall involvement"],
    ["Stage IIIC", "Any T, N3 M0", "~49%", "Extensive nodal disease"],
    ["Stage IV", "Any T, Any N, M1", "~29%", "Distant metastases"],
  ],
  "Survival data from ACS SEER database. Emphasize that staging drives treatment: Stage I-IIA = potentially curable with surgery ± adjuvant; Stage III = neoadjuvant chemotherapy often first; Stage IV = palliative intent. The 'curable' vs 'palliative' distinction is clinically and emotionally significant for patient counseling."
);

// SLIDE 26: Prognostic Factors
contentSlide(
  "Prognostic & Predictive Factors",
  [
    { text: "Strongest Prognostic Factors (predict OUTCOME)", bold: true, sub: [
      "Axillary lymph node status: MOST important prognostic factor",
      "Tumor size (T stage)",
      "Histological grade (Nottingham)",
      "Lymphovascular invasion (LVI)",
      "ER/PR/HER2 status",
      "Ki-67 proliferation index",
    ]},
    { text: "Predictive Factors (predict TREATMENT RESPONSE)", bold: true, sub: [
      "ER/PR +ve → will respond to hormone therapy (tamoxifen, aromatase inhibitors)",
      "HER2 +ve → will respond to trastuzumab (Herceptin), pertuzumab, T-DM1",
      "BRCA1/2 mutation → will respond to PARP inhibitors (olaparib, talazoparib)",
      "PD-L1 expression → may benefit from immunotherapy (pembrolizumab in TNBC)",
    ]},
    { text: "Genomic Assays (when criteria met)", bold: true, sub: [
      "Oncotype DX (21-gene recurrence score): guides chemo decision in ER+, HER2–, N0-N1",
      "PAM50/Prosigna: molecular subtyping; MammaPrint: risk stratification",
    ]},
  ],
  "Distinguish prognostic vs predictive factors – this is a common exam distinction. Prognostic = tells you how the patient will do regardless of treatment. Predictive = tells you whether a specific treatment will work. ER status is BOTH prognostic (better outcome in ER+ cancer) and predictive (responds to tamoxifen)."
);

// SLIDE 27: SECTION – Treatment
sectionDivider("SECTION 6", "Treatment of Breast Cancer");

// SLIDE 28: Treatment Overview
contentSlide(
  "Overview of Breast Cancer Treatment",
  [
    { text: "Multimodal Approach – Individualized to Stage & Molecular Subtype", bold: true, sub: [] },
    { text: "Local Treatment (controls primary tumor & regional nodes)", bold: true, sub: [
      "Surgery: Breast-conserving surgery (BCS/lumpectomy) OR mastectomy + axillary surgery",
      "Radiotherapy: Post-operative RT to breast/chest wall and/or regional nodes",
    ]},
    { text: "Systemic Treatment (addresses micrometastatic disease)", bold: true, sub: [
      "Chemotherapy: Anthracyclines (AC), taxanes (paclitaxel, docetaxel); neoadjuvant or adjuvant",
      "Endocrine therapy: Tamoxifen (pre-menopausal) / Aromatase inhibitors (post-menopausal)",
      "Targeted therapy: Trastuzumab (Herceptin), pertuzumab, T-DM1, lapatinib for HER2+",
      "Immunotherapy: Pembrolizumab for TNBC (PD-L1+) and early high-risk TNBC",
      "PARP inhibitors: Olaparib/talazoparib for BRCA-mutated HER2-negative MBC",
      "CDK4/6 inhibitors: Palbociclib, ribociclib, abemaciclib for HR+/HER2– metastatic disease",
    ]},
    { text: "Supportive Care", bold: true, sub: [
      "Bone-modifying agents (bisphosphonates, denosumab) for bone metastases",
      "Palliative care integration from diagnosis onwards",
    ]},
  ],
  "Treatment decisions are made by a multidisciplinary team (MDT): surgeon, medical oncologist, radiation oncologist, pathologist, radiologist, plastic surgeon, psychologist. Emphasize to students that NO single specialist manages breast cancer alone."
);

// SLIDE 29: Surgery
twoColSlide(
  "Surgical Treatment of Breast Cancer",
  "Breast Surgery Options",
  [
    "BCS (Lumpectomy / Wide Local Excision):",
    "  → Removal of tumor + 2mm clear margins",
    "  → ALWAYS followed by whole-breast RT",
    "  → Equivalent survival to mastectomy (NSABP B-06 trial)",
    "  → Preferred when tumor:breast ratio favorable",
    "",
    "Simple/Total Mastectomy: removal of entire breast only",
    "Modified Radical Mastectomy (MRM):",
    "  → Breast + axillary lymph nodes (Level I–III)",
    "  → Pectoralis major PRESERVED (Patey/Auchincloss)",
    "Skin-sparing / Nipple-sparing mastectomy: for immediate reconstruction",
    "Bilateral prophylactic mastectomy: BRCA carriers",
  ],
  "Axillary Surgery",
  [
    "Sentinel Lymph Node Biopsy (SLNB):",
    "  → Standard of care for clinically node-negative disease",
    "  → Blue dye ± radioisotope (Tc-99m) injection periareolar",
    "  → First draining node removed and intraoperatively assessed",
    "  → If negative → no axillary clearance needed",
    "",
    "Axillary Lymph Node Dissection (ALND):",
    "  → Level I, II, III nodes removed",
    "  → Performed if SLNB positive or clinically N+ disease",
    "  → Complications: lymphedema, nerve injury, seroma",
  ],
  "NSABP B-06 trial (Fisher et al.) – landmark RCT showing BCS + RT = mastectomy in survival for Stage I-II breast cancer. SLNB revolutionized axillary management. Complications of ALND to know: lymphedema (5–10% severe), winged scapula (long thoracic nerve injury), seroma formation."
);

// SLIDE 30: Chemotherapy
contentSlide(
  "Chemotherapy Regimens",
  [
    { text: "Indications for Chemotherapy", bold: true, sub: [
      "Triple-negative breast cancer (all stages ≥ T1b N0)",
      "HER2+ breast cancer (with targeted therapy)",
      "High-risk ER+ cancer (high grade, node positive, high Oncotype score)",
      "Neoadjuvant: large/locally advanced tumors (Stage III), to downstage for BCS",
    ]},
    { text: "Standard Regimens", bold: true, sub: [
      "AC × 4 → Paclitaxel × 4 (dose-dense or weekly): most common",
      "TC (Docetaxel + Cyclophosphamide) × 4–6 cycles: low-risk, node-negative",
      "FEC-D (5-FU, Epirubicin, Cyclophosphamide → Docetaxel): European protocol",
      "AC-T + Trastuzumab + Pertuzumab: for HER2+ (CLEOPATRA/APHINITY protocol)",
      "Carboplatin + Paclitaxel + Pembrolizumab: TNBC neoadjuvant (KEYNOTE-522)",
    ]},
    { text: "Common Side Effects", bold: true, sub: [
      "Nausea/vomiting (serotonin antagonists), alopecia, myelosuppression (G-CSF support)",
      "Anthracycline: cardiotoxicity – LVEF monitoring",
      "Taxanes: peripheral neuropathy, nail changes",
    ]},
  ],
  "Neoadjuvant chemotherapy (NACT) is now preferred for Stage II-III breast cancer. A pathologic complete response (pCR) after NACT = no residual invasive tumor in breast and nodes – is a surrogate for improved survival, especially in TNBC and HER2+ subtypes."
);

// SLIDE 31: Endocrine & Targeted Therapy
twoColSlide(
  "Endocrine Therapy & Targeted Therapy",
  "Endocrine (Hormone) Therapy – ER/PR+",
  [
    "Pre-menopausal: Tamoxifen 20mg/day × 5–10 years",
    "  → SERM (Selective Estrogen Receptor Modulator)",
    "  → Side effects: hot flushes, endometrial cancer risk, DVT",
    "Post-menopausal: Aromatase inhibitors (AIs)",
    "  → Anastrozole, letrozole, exemestane × 5–10 years",
    "  → Block peripheral estrogen synthesis in fat",
    "  → Superior to tamoxifen in post-menopausal women",
    "  → Side effects: arthralgias, osteoporosis",
    "Ovarian suppression (GnRH agonists: goserelin) + AI or tamoxifen in high-risk pre-menopausal patients",
    "CDK4/6 inhibitors (palbociclib + AI): HR+/HER2– metastatic disease – major OS benefit",
  ],
  "Targeted Therapy – HER2+",
  [
    "Trastuzumab (Herceptin): monoclonal Ab against HER2 ECD",
    "  → 1 year adjuvant; reduces recurrence by 50%",
    "  → Cardiac monitoring essential",
    "Pertuzumab (Perjeta): blocks HER2-HER3 dimerization",
    "  → Combined with trastuzumab + docetaxel (THP) – neoadjuvant/adjuvant",
    "T-DM1 (Kadcyla): trastuzumab + chemotherapy conjugate",
    "  → For residual disease after NACT",
    "T-DXd (Enhertu): HER2-low disease and HER2+ MBC",
    "Lapatinib: oral TKI; CNS penetration; brain metastases",
    "Neratinib: extended adjuvant after trastuzumab in HER2+",
  ],
  "Trastuzumab transformed HER2+ breast cancer from the worst to a manageable subtype. Mechanism: binds HER2 extracellular domain → ADCC + inhibits PI3K/AKT pathway. T-DM1 and T-DXd are 'antibody-drug conjugates' – explain the concept of a guided missile delivering chemotherapy directly to HER2-expressing cells."
);

// SLIDE 32: Radiotherapy
contentSlide(
  "Radiotherapy in Breast Cancer",
  [
    { text: "Indications", bold: true, sub: [
      "MANDATORY after BCS (whole breast RT): reduces local recurrence from 30% to <10%",
      "After mastectomy with ≥4 positive nodes or T3/T4 disease (PMRT – post-mastectomy RT)",
      "Regional nodal RT: if axillary, internal mammary, or supraclavicular nodes involved",
      "Palliative RT: bone pain, brain metastases, fungating wounds",
    ]},
    { text: "Standard Schedules", bold: true, sub: [
      "Conventional: 50 Gy in 25 fractions over 5 weeks",
      "Hypofractionated (UK/START B): 40 Gy in 15 fractions – now preferred in most centers",
      "Accelerated partial breast irradiation (APBI): selected low-risk, older patients",
      "Boost: additional dose (10–16 Gy) to tumor bed – reduces local recurrence in young patients",
    ]},
    { text: "Side Effects", bold: true, sub: [
      "Acute: skin erythema, desquamation, fatigue",
      "Late: fibrosis, lymphedema, rib fractures, radiation pneumonitis, cardiac toxicity (left-sided RT)",
      "Rare but serious: radiation-induced sarcoma, brachial plexopathy",
    ]},
  ],
  "Meta-analysis by Early Breast Cancer Trialists' Collaborative Group (EBCTCG) established that RT after BCS saves lives – it reduces breast cancer mortality and is not just a cosmetic consideration. Modern techniques (IMRT, prone positioning for left-sided) reduce cardiac dose significantly."
);

// SLIDE 33: SECTION – Special Situations
sectionDivider("SECTION 7", "Special Situations & Screening");

// SLIDE 34: Locally Advanced & Inflammatory
contentSlide(
  "Locally Advanced & Inflammatory Breast Cancer",
  [
    { text: "Locally Advanced Breast Cancer (LABC) – Stage III", bold: true, sub: [
      "T3-T4 tumors, fixed axillary nodes (N2), or supraclavicular nodes (N3)",
      "Treatment: NACT first → re-assess → surgery → RT → adjuvant systemic therapy",
      "Goal: downstage to allow surgical resection; assess chemosensitivity",
    ]},
    { text: "Inflammatory Breast Cancer (IBC) – T4d", bold: true, sub: [
      "Clinical diagnosis: erythema + peau d'orange involving >1/3 of breast skin, onset <6 months",
      "Often NO palpable lump; easily confused with mastitis",
      "Pathology: dermal lymphatic tumor emboli (NOT required for diagnosis)",
      "Always Stage IIIB or higher at presentation",
      "Treatment: NACT → MRM (BCS NOT appropriate) → RT → adjuvant therapy",
      "Most aggressive breast cancer; median survival ~2.5 years historically",
    ]},
    { text: "Breast Cancer in Pregnancy", bold: true, sub: [
      "Most common cancer in pregnancy; 1 in 3000 pregnancies",
      "Chemotherapy safe in 2nd and 3rd trimester (avoid 1st trimester)",
      "Tamoxifen and RT contraindicated in pregnancy",
    ]},
  ],
  "IBC is a clinical diagnosis – do NOT wait for biopsy confirmation before starting treatment. The defining feature is the rapid skin change, not a mass. Emphasize: always consider IBC in any woman with a red, swollen breast who does not respond to antibiotics within 1 week – it is NOT simple mastitis until proven otherwise."
);

// SLIDE 35: Screening & Prevention
contentSlide(
  "Breast Cancer Screening & Prevention",
  [
    { text: "Screening Guidelines", bold: true, sub: [
      "Average risk: Mammography every 1–2 years from age 40–50 onwards (varies by country)",
      "High risk (BRCA+, family history): Annual MRI + mammography from age 25–30",
      "Breast self-examination (BSE): monthly, 5–10 days after menstruation; less evidence-based but promotes awareness",
      "Clinical breast examination (CBE): every 1–3 years (age 25–40); annually (>40)",
    ]},
    { text: "Chemoprevention", bold: true, sub: [
      "Tamoxifen 20 mg/day × 5 years: ↓ risk by ~38% in high-risk pre-menopausal women",
      "Raloxifene: similar benefit in post-menopausal women; ↓ uterine cancer risk vs tamoxifen",
      "Aromatase inhibitors (anastrozole, exemestane): highly effective in post-menopausal high-risk women",
    ]},
    { text: "Lifestyle Modifications", bold: true, sub: [
      "Maintain healthy weight (BMI 18.5–24.9), especially post-menopause",
      "Regular physical activity: 150 min/week moderate exercise → ↓ risk by 20–25%",
      "Limit alcohol intake; avoid smoking",
      "Breastfeed if possible (each year of breastfeeding ↓ risk by ~4.3%)",
    ]},
  ],
  "India currently lacks a national organized mammographic screening program. However, CBE-based screening programs have shown benefit in resource-limited settings (Mumbai-TIFR trial). Emphasize to students: educate ALL female patients about breast awareness, regardless of age."
);

// SLIDE 36: Metastatic Breast Cancer
contentSlide(
  "Metastatic Breast Cancer (Stage IV)",
  [
    { text: "Common Sites of Metastasis", bold: true, sub: [
      "Bone (most common – 60–70%): osteolytic lesions, pathological fractures, hypercalcemia",
      "Lung / pleura: dyspnea, pleural effusion, cough",
      "Liver: hepatomegaly, jaundice, elevated LFTs",
      "Brain: headache, seizures, neurological deficits",
      "Lymph nodes: supraclavicular, mediastinal",
    ]},
    { text: "Management Principles", bold: true, sub: [
      "Intent: PALLIATIVE (not curative), but can achieve long remissions (years in HR+ disease)",
      "Repeat biopsy of metastasis (receptor status may change from primary)",
      "HR+/HER2–: CDK4/6 inhibitor + endocrine therapy (palbociclib + letrozole)",
      "HER2+: Trastuzumab + pertuzumab + taxane (THP); T-DM1, T-DXd later lines",
      "TNBC: Pembrolizumab + chemo (PD-L1+); sacituzumab govitecan; olaparib (BRCA+)",
    ]},
    { text: "Supportive Care", bold: true, sub: [
      "Bisphosphonates (zoledronic acid) or denosumab for bone metastases",
      "Radiation for bone pain, brain metastases",
      "Palliative care: pain, nausea, psychological support from diagnosis",
    ]},
  ],
  "A small percentage (~5%) of metastatic HR+ breast cancer patients become 'exceptional responders' and survive >10 years with disease. This gives hope for patients but should not create unrealistic expectations. CDK4/6 inhibitors (PALOMA-2, MONALEESA-2 trials) have dramatically changed the landscape of ER+ MBC."
);

// SLIDE 37: Summary
contentSlide(
  "Summary – Key Take-Home Points",
  [
    "Breast cancer is the most common cancer in women; early detection saves lives",
    "Anatomy: breast has 15–20 lobes, TDLU is the origin of most cancers; axilla drains 75% of lymph",
    "CBE: systematic inspection (4 positions) + palpation (3-finger, clock method) + axillary exam",
    "Triple Assessment (Clinical + Imaging + Biopsy) is the diagnostic standard with ~100% accuracy",
    "Most common type: Invasive Ductal Carcinoma / NST (75%); most aggressive: TNBC and inflammatory CA",
    "Molecular subtypes guide systemic treatment: ER/PR/HER2/Ki-67 must be reported on every biopsy",
    "Strongest prognostic factor: axillary lymph node status",
    "BCS + RT = Mastectomy in survival for Stage I-II (NSABP B-06)",
    "SLNB has replaced routine ALND for clinically node-negative patients",
    "Targeted therapies (trastuzumab, CDK4/6 inhibitors) have transformed breast cancer outcomes",
    "Screen women: mammography from 40-50; MRI for BRCA carriers from age 25-30",
  ],
  "End the lecture with a clinical case discussion – present a 45-year-old woman with a hard, irregular right breast lump, axillary nodes, and inverted nipple. Walk through clinical examination, triple assessment, staging, and treatment planning as a group exercise."
);

// SLIDE 38: MCQ Teaser
contentSlide(
  "Quick Quiz – Test Your Knowledge!",
  [
    "Q1. Which lymph node group receives the majority (~75%) of breast lymphatic drainage?",
    "     A. Internal mammary    B. Axillary    C. Supraclavicular    D. Infraclavicular",
    "",
    "Q2. A 28-year-old woman has a well-defined, mobile, non-tender breast lump. Best first investigation?",
    "     A. Mammogram    B. MRI    C. Ultrasound    D. FNAC",
    "",
    "Q3. Which receptor status is associated with the WORST prognosis in breast cancer?",
    "     A. ER+/PR+/HER2–    B. ER–/PR–/HER2+    C. ER–/PR–/HER2–    D. ER+/PR+/HER2+",
    "",
    "Q4. After BCS for Stage I breast cancer, what is MANDATORY?",
    "     A. Axillary dissection    B. Radiotherapy    C. Chemotherapy    D. Endocrine therapy",
  ],
  "Answers: Q1 = B (Axillary nodes), Q2 = C (Ultrasound – young woman with dense breasts), Q3 = C (Triple negative), Q4 = B (Radiotherapy after BCS is mandatory to reduce local recurrence). Use this as an audience participation activity."
);

// SLIDE 39: References
contentSlide(
  "References & Further Reading",
  [
    "Bailey & Love's Short Practice of Surgery, 28th Edition (2023) – Chapter 58: Breast Disease",
    "Robbins, Cotran & Kumar: Pathologic Basis of Disease, 10th Edition (2025) – Chapter 23: Breast",
    "Schwartz's Principles of Surgery, 11th Edition – Breast Chapter",
    "Harrison's Principles of Internal Medicine, 22nd Edition (2025) – Breast Cancer",
    "AJCC Cancer Staging Manual, 8th Edition (2017)",
    "NCCN Clinical Practice Guidelines in Oncology – Breast Cancer v.4.2025",
    "Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Meta-analyses",
    "NSABP B-06 Trial: Fisher B et al. (NEJM 2002) – BCS vs Mastectomy",
    "KEYNOTE-522: Schmid P et al. (NEJM 2022) – Pembrolizumab in TNBC",
    "PALOMA-2 Trial: Finn RS et al. (NEJM 2016) – Palbociclib + Letrozole in HR+ MBC",
  ],
  "Encourage students to access the NCCN guidelines freely online at nccn.org for the most up-to-date treatment algorithms. The EBCTCG meta-analyses are landmark papers that established the evidence base for RT, chemotherapy, and endocrine therapy in early breast cancer."
);

// SLIDE 40: Thank You
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finalSlide.addShape(pres.shapes.RECTANGLE, { x: 0.18, y: 0, w: 9.82, h: 0.08, fill: { color: C.accent } });
finalSlide.addText("THANK YOU", {
  x: 0.5, y: 1.2, w: 9, h: 1.4,
  fontSize: 56, color: C.white, bold: true, align: "center",
});
finalSlide.addText("Questions & Discussion Welcome", {
  x: 0.5, y: 2.7, w: 9, h: 0.6,
  fontSize: 22, color: C.accentSoft, align: "center", italic: true,
});
finalSlide.addShape(pres.shapes.RECTANGLE, { x: 3, y: 3.45, w: 4, h: 0.05, fill: { color: C.gold } });
finalSlide.addText("\"Early detection is the best protection\"\n– Breast Cancer Awareness", {
  x: 1, y: 3.7, w: 8, h: 0.9,
  fontSize: 14, color: C.lightGray, align: "center", italic: true,
});
finalSlide.addText("🎗  Breast Cancer Awareness  🎗", {
  x: 1, y: 4.7, w: 8, h: 0.5,
  fontSize: 13, color: C.accentSoft, align: "center",
});
finalSlide.addNotes("Open the floor for questions. Suggested discussion topics: 1) Case-based scenario, 2) BRCA counselling scenario, 3) Explain treatment to a patient simulation. Thank students for their attention.");

// Write file
pres.writeFile({ fileName: "/home/daytona/workspace/breast-cancer-lecture/Breast_Cancer_Lecture_MBBS.pptx" })
  .then(() => console.log("PPT created successfully!"))
  .catch(err => console.error("Error:", err));

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm
from reportlab.platypus import (SimpleDocTemplate, Paragraph, Spacer, Table,
                                 TableStyle, HRFlowable, PageBreak)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY

# ─── Document ─────────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    "/home/daytona/workspace/breast-cancer-lecture/Breast_Cancer_MCQ_Student_Handout.pdf",
    pagesize=A4,
    topMargin=2*cm, bottomMargin=2*cm,
    leftMargin=2.2*cm, rightMargin=2.2*cm,
    title="Breast Cancer – MCQ Student Handout",
    author="Medical College, Department of Surgery"
)

# ─── Styles ──────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

NAVY  = colors.HexColor("#0D1B2A")
RED   = colors.HexColor("#E63946")
GOLD  = colors.HexColor("#F4C430")
TEAL  = colors.HexColor("#2EC4B6")
LGRAY = colors.HexColor("#F0F4F8")
DGRAY = colors.HexColor("#4A4A6A")

title_style = ParagraphStyle("title", parent=styles["Title"],
    fontSize=20, textColor=NAVY, spaceAfter=4, alignment=TA_CENTER, leading=26)

subtitle_style = ParagraphStyle("subtitle", parent=styles["Normal"],
    fontSize=11, textColor=RED, spaceAfter=2, alignment=TA_CENTER, italic=True)

section_style = ParagraphStyle("section", parent=styles["Heading2"],
    fontSize=13, textColor=RED, spaceBefore=14, spaceAfter=6,
    borderPad=4, leftIndent=0, fontName="Helvetica-Bold")

q_style = ParagraphStyle("question", parent=styles["Normal"],
    fontSize=10.5, textColor=NAVY, spaceBefore=10, spaceAfter=3,
    fontName="Helvetica-Bold", leading=14)

opt_style = ParagraphStyle("option", parent=styles["Normal"],
    fontSize=10, textColor=colors.HexColor("#1A1A2E"), leftIndent=18,
    spaceAfter=1.5, leading=13)

ans_style = ParagraphStyle("answer", parent=styles["Normal"],
    fontSize=10, textColor=colors.HexColor("#006400"), fontName="Helvetica-Bold",
    leftIndent=18, spaceAfter=1)

exp_style = ParagraphStyle("explanation", parent=styles["Normal"],
    fontSize=9.5, textColor=DGRAY, leftIndent=18, spaceAfter=4,
    italic=True, leading=13)

body_style = ParagraphStyle("body", parent=styles["Normal"],
    fontSize=10, textColor=NAVY, spaceAfter=4, leading=14, alignment=TA_JUSTIFY)

note_style = ParagraphStyle("note", parent=styles["Normal"],
    fontSize=9, textColor=DGRAY, italic=True, leftIndent=10, spaceAfter=2)

# ─── Content ─────────────────────────────────────────────────────────────────
story = []

# Header table (color banner)
header_data = [[Paragraph("<font color='white'><b>DEPARTMENT OF SURGERY &amp; ONCOLOGY</b></font>",
                            ParagraphStyle("hdr", fontSize=9, textColor=colors.white, alignment=TA_CENTER))]]
header_table = Table(header_data, colWidths=[17*cm])
header_table.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), NAVY),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
]))
story.append(header_table)
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("BREAST CANCER", title_style))
story.append(Paragraph("Student Assessment Handout — MCQ &amp; Short Answer Questions", subtitle_style))
story.append(Spacer(1, 0.2*cm))

# Info table
info_data = [
    ["Course:", "MBBS Final Year — Surgery", "Date:", "_______________"],
    ["Roll No.:", "_______________", "Total Marks:", "50"],
    ["Time Allowed:", "45 minutes", "Passing Marks:", "35 (70%)"],
]
info_table = Table(info_data, colWidths=[3.5*cm, 5.5*cm, 3*cm, 5*cm])
info_table.setStyle(TableStyle([
    ("FONTNAME", (0,0), (-1,-1), "Helvetica"),
    ("FONTSIZE", (0,0), (-1,-1), 9.5),
    ("FONTNAME", (0,0), (0,-1), "Helvetica-Bold"),
    ("FONTNAME", (2,0), (2,-1), "Helvetica-Bold"),
    ("TEXTCOLOR", (0,0), (-1,-1), NAVY),
    ("BACKGROUND", (0,0), (-1,-1), LGRAY),
    ("BOX", (0,0), (-1,-1), 0.5, colors.HexColor("#CCCCCC")),
    ("INNERGRID", (0,0), (-1,-1), 0.3, colors.HexColor("#DDDDDD")),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 8),
]))
story.append(info_table)
story.append(Spacer(1, 0.3*cm))
story.append(HRFlowable(width="100%", thickness=2, color=RED))
story.append(Spacer(1, 0.2*cm))

story.append(Paragraph(
    "<b>Instructions:</b> Each MCQ has ONE best answer. Circle the letter of the correct answer. "
    "For short answer questions, write concise answers. No negative marking.",
    note_style))
story.append(Spacer(1, 0.3*cm))

# ─── SECTION A: MCQs ─────────────────────────────────────────────────────────
story.append(Paragraph("SECTION A: Multiple Choice Questions (1 mark each) — 30 marks", section_style))
story.append(HRFlowable(width="100%", thickness=0.5, color=TEAL))
story.append(Spacer(1, 0.2*cm))

mcqs = [
    # (Question, [Options], Correct letter, Explanation)

    # ANATOMY
    ("1. The majority (~75%) of lymphatic drainage from the breast flows to which lymph node group?",
     ["A. Internal mammary nodes", "B. Axillary nodes", "C. Supraclavicular nodes", "D. Infraclavicular nodes"],
     "B",
     "The axillary nodes receive ~75% of lymphatic drainage. The internal mammary nodes receive ~25% (mainly from medial breast quadrants)."),

    ("2. Which structure connects the skin of the breast to the deep fascia and, when invaded by tumor, causes skin dimpling?",
     ["A. Glands of Montgomery", "B. Lactiferous sinuses", "C. Cooper's ligaments", "D. Pectoral fascia"],
     "C",
     "Cooper's suspensory ligaments, when infiltrated by carcinoma, become shortened and cause the characteristic skin dimpling sign."),

    ("3. The 'terminal duct lobular unit' (TDLU) is significant in breast cancer because:",
     ["A. It is the site of origin of most breast carcinomas", "B. It produces only benign lesions",
      "C. It drains directly to the supraclavicular nodes", "D. It is only present in lactating breasts"],
     "A",
     "The TDLU is the functional unit of the breast and is the site of origin of both ductal and lobular carcinomas."),

    ("4. Injury to the long thoracic nerve during axillary lymph node dissection results in:",
     ["A. Loss of sensation in the inner arm", "B. Winged scapula",
      "C. Weakened shoulder extension", "D. Lymphedema of the arm"],
     "B",
     "The long thoracic nerve (C5-C7) supplies serratus anterior. Division causes winging of the scapula – a recognized complication of axillary clearance."),

    ("5. In which quadrant of the breast does cancer most commonly arise?",
     ["A. Lower inner quadrant (LIQ)", "B. Lower outer quadrant (LOQ)",
      "C. Upper outer quadrant (UOQ)", "D. Central/subareolar"],
     "C",
     "~50% of breast cancers arise in the upper outer quadrant (UOQ) as it contains the most glandular tissue and is closest to the axilla."),

    # RISK FACTORS & PATHOLOGY
    ("6. A 35-year-old woman is found to carry a BRCA1 mutation. What is her approximate lifetime risk of developing breast cancer?",
     ["A. 10–15%", "B. 20–30%", "C. 50–55%", "D. 65–75%"],
     "D",
     "BRCA1 mutation carriers have a lifetime breast cancer risk of approximately 65–72%. BRCA2 carriers have ~69% lifetime risk."),

    ("7. Which molecular subtype of breast cancer is characterized by ER–, PR–, HER2– and carries the WORST prognosis?",
     ["A. Luminal A", "B. Luminal B (HER2+)", "C. HER2-enriched", "D. Triple-negative (TNBC)"],
     "D",
     "Triple-negative breast cancer (TNBC) lacks all three receptors, responds only to chemotherapy, and has the worst prognosis among molecular subtypes. It is associated with BRCA1 mutations."),

    ("8. Paget's disease of the nipple is characterized by:",
     ["A. Lobular carcinoma in situ with nipple involvement",
      "B. Eczematoid change of the nipple with underlying DCIS or invasive carcinoma",
      "C. Fat necrosis of the areola",
      "D. Benign duct ectasia presenting as nipple discharge"],
     "B",
     "Paget's disease presents as persistent eczema of the nipple-areola complex. It contains Paget cells (large clear intraepithelial cells) and is always associated with underlying DCIS or invasive carcinoma."),

    ("9. Inflammatory breast cancer (IBC) is BEST characterized by:",
     ["A. A rapidly growing large palpable mass > 5 cm", "B. Always HER2-positive status",
      "C. Erythema and peau d'orange involving ≥1/3 of the breast skin",
      "D. Granulomatous inflammation on histology"],
     "C",
     "IBC is a clinical diagnosis based on erythema and skin changes (peau d'orange) involving >1/3 of the breast skin with onset <6 months. Dermal lymphatic tumor emboli may or may not be found on biopsy."),

    ("10. The Nottingham grading system scores which THREE histological features?",
     ["A. Tumor size, node status, mitosis", "B. Tubule formation, nuclear pleomorphism, mitotic count",
      "C. ER status, HER2 amplification, Ki-67", "D. Tumor necrosis, vascular invasion, calcification"],
     "B",
     "The Nottingham (Elston-Ellis) system scores 3 features (each 1–3): tubule/gland formation, nuclear pleomorphism, and mitotic count. Total score: 3–5=Grade 1, 6–7=Grade 2, 8–9=Grade 3."),

    # CLINICAL EXAMINATION
    ("11. Clinical breast examination should ideally be performed at which point in the menstrual cycle?",
     ["A. Day 1–3 (during menstruation)", "B. Days 5–10 (follicular phase)",
      "C. Days 14–16 (ovulation)", "D. Days 20–28 (luteal phase)"],
     "B",
     "Days 5–10 (follicular phase, after menstruation) is ideal as there is minimal hormonal influence on breast tissue, reducing physiological nodularity and tenderness."),

    ("12. 'Tethering' of a breast lump means:",
     ["A. The lump is mobile in all planes", "B. The lump is completely fixed to the chest wall",
      "C. Movement is restricted in one plane (skin involvement)", "D. The lump is attached to the nipple"],
     "C",
     "Tethering = restricted mobility in ONE plane due to Cooper's ligament or skin involvement. Fixed = completely immobile in ALL planes due to chest wall (pectoralis) invasion."),

    ("13. A 45-year-old woman is found to have peau d'orange affecting half the breast skin with satellite nodules. This is classified as:",
     ["A. T2 disease", "B. T3 disease", "C. T4b disease", "D. T4d (inflammatory carcinoma)"],
     "C",
     "T4b = ulceration, skin nodules, or edema (peau d'orange) of the skin NOT meeting criteria for inflammatory carcinoma. T4d specifically = inflammatory carcinoma (erythema + peau d'orange ≥1/3 of skin, onset <6 months)."),

    ("14. The triple assessment includes which combination?",
     ["A. Mammography + MRI + PET scan", "B. Clinical examination + Imaging + Tissue biopsy",
      "C. Ultrasound + CT + FNAC", "D. Physical examination + Blood tests + Bone scan"],
     "B",
     "Triple assessment = (1) Clinical examination, (2) Radiological imaging (mammography/ultrasound), and (3) Tissue sampling (FNAC/core biopsy). This combination has ~100% diagnostic accuracy."),

    ("15. A young woman of 28 presents with a smooth, well-defined, mobile, non-tender lump in the breast. The MOST appropriate FIRST imaging investigation is:",
     ["A. Mammography", "B. MRI of the breast", "C. Ultrasound", "D. PET-CT"],
     "C",
     "In women <40 years, ultrasound is preferred as dense breast tissue reduces mammographic sensitivity. USG can distinguish cystic from solid lesions and characterize solid lesions (fibroadenoma vs malignancy)."),

    # STAGING & TREATMENT
    ("16. A patient has a 3 cm breast tumor with TWO mobile ipsilateral axillary nodes and NO distant metastases. What is her TNM stage?",
     ["A. T2 N1 M0 – Stage IIA", "B. T2 N1 M0 – Stage IIB",
      "C. T2 N2 M0 – Stage IIIA", "D. T3 N1 M0 – Stage IIIA"],
     "B",
     "T2 (2–5 cm) + N1 (mobile ipsilateral axillary nodes, Level I/II) + M0 = Stage IIB. Note: T1 N1 M0 = Stage IIA; T2 N1 M0 = Stage IIB."),

    ("17. The NSABP B-06 trial established that:",
     ["A. Mastectomy is superior to BCS in survival",
      "B. BCS + radiotherapy has equivalent survival to modified radical mastectomy for Stage I-II breast cancer",
      "C. Adjuvant chemotherapy is mandatory after BCS",
      "D. Sentinel node biopsy should replace ALND in all patients"],
     "B",
     "NSABP B-06 (Fisher et al.) was the landmark RCT showing that BCS + radiotherapy = mastectomy in terms of overall and disease-free survival for Stage I–II breast cancer."),

    ("18. Trastuzumab (Herceptin) is indicated in breast cancer that is:",
     ["A. ER positive", "B. PR positive", "C. HER2 positive", "D. Triple negative"],
     "C",
     "Trastuzumab is a monoclonal antibody targeting the HER2 receptor extracellular domain. It is indicated in HER2-overexpressing (IHC 3+ or FISH-amplified) breast cancers."),

    ("19. Which statement about Sentinel Lymph Node Biopsy (SLNB) is CORRECT?",
     ["A. It is contraindicated in T1 breast cancer",
      "B. It requires removal of all Level I–III axillary nodes",
      "C. Blue dye or radioisotope is injected to identify the first draining lymph node",
      "D. A positive SLNB always requires immediate axillary clearance"],
     "C",
     "SLNB uses blue dye and/or Tc-99m radioisotope to identify and remove the first draining lymph node(s). If negative, no further axillary surgery is required, sparing patients the morbidity of ALND."),

    ("20. Tamoxifen works by which mechanism?",
     ["A. Inhibiting aromatase enzyme in peripheral adipose tissue",
      "B. Acting as a selective estrogen receptor modulator (SERM) – blocking ER in breast tissue",
      "C. Blocking HER2 receptor dimerization",
      "D. Inhibiting CDK4/6 cell cycle kinases"],
     "B",
     "Tamoxifen is a SERM. It competitively blocks estrogen receptors in breast tissue (antagonist effect) but acts as a partial agonist in uterus and bone. Side effects include hot flashes, DVT, and endometrial cancer."),

    # MORE CLINICAL
    ("21. Blood-stained nipple discharge in a 50-year-old woman is MOST likely due to:",
     ["A. Lactational mastitis", "B. Galactorrhea from prolactinoma",
      "C. Intraductal papilloma or DCIS", "D. Fibroadenoma"],
     "C",
     "Blood-stained or serosanguineous discharge is most commonly from intraductal papilloma or DCIS. All cases require investigation with ductography/ductoscopy and biopsy."),

    ("22. Post-mastectomy radiotherapy (PMRT) is indicated when:",
     ["A. The tumor is T1 with no nodes involved",
      "B. There are ≥4 positive axillary nodes OR T3/T4 disease",
      "C. The patient is under 40 years of age",
      "D. The patient has triple-negative subtype regardless of stage"],
     "B",
     "PMRT indications: ≥4 positive axillary nodes, T3/T4 tumor, or 1–3 positive nodes with adverse features. It reduces locoregional recurrence and improves survival."),

    ("23. The MOST powerful independent prognostic factor in breast cancer is:",
     ["A. Tumor grade", "B. Tumor size", "C. Axillary lymph node status", "D. HER2 status"],
     "C",
     "Axillary lymph node status is the single most powerful prognostic factor in breast cancer. Node-negative disease has significantly better survival than node-positive disease, regardless of tumor size or grade."),

    ("24. Which drug is a CDK4/6 inhibitor used in HR+/HER2– metastatic breast cancer?",
     ["A. Tamoxifen", "B. Trastuzumab", "C. Palbociclib", "D. Pembrolizumab"],
     "C",
     "Palbociclib (Ibrance) is a CDK4/6 inhibitor. Combined with letrozole or fulvestrant, it significantly extends PFS in HR+/HER2– metastatic breast cancer (PALOMA-2 trial)."),

    ("25. A BRCA-negative woman with early-stage breast cancer has Oncotype DX Recurrence Score of 12. The recommended treatment is:",
     ["A. Chemotherapy + hormone therapy", "B. Hormone therapy alone (no chemo)",
      "C. Chemotherapy alone", "D. Observation only"],
     "B",
     "TAILORx trial: Oncotype DX RS 0–25 in postmenopausal/intermediate-risk patients → endocrine therapy alone is non-inferior to chemo + endocrine therapy. RS <18 = very low risk; hormone therapy alone is appropriate."),

    ("26. Which of the following is an ABSOLUTE indication for genetic counseling and BRCA testing?",
     ["A. Any woman over 40 with breast cancer",
      "B. A woman with breast cancer diagnosed before age 40 with a first-degree relative with ovarian cancer",
      "C. A woman with ER-positive breast cancer",
      "D. A postmenopausal woman on HRT who develops breast cancer"],
     "B",
     "BRCA testing is indicated when there is: early-onset breast cancer (<40), family history of breast/ovarian cancer, bilateral breast cancer, male breast cancer, or Ashkenazi Jewish ancestry. The combination of early onset + family history of ovarian cancer is a strong indication."),

    ("27. Aromatase inhibitors (e.g., anastrozole, letrozole) are preferred over tamoxifen in which group?",
     ["A. Pre-menopausal women with ER+ breast cancer",
      "B. Post-menopausal women with ER+ breast cancer",
      "C. All women with HER2+ breast cancer",
      "D. Women with triple-negative breast cancer"],
     "B",
     "Aromatase inhibitors block peripheral estrogen synthesis (in adipose tissue) and are only effective in post-menopausal women where ovarian estrogen production has ceased. They are superior to tamoxifen in post-menopausal ER+ breast cancer."),

    ("28. A patient with BI-RADS score 5 on mammography should have:",
     ["A. Routine 12-month follow-up imaging",
      "B. 6-month follow-up imaging",
      "C. Immediate core needle biopsy",
      "D. CT-guided biopsy only"],
     "C",
     "BI-RADS 5 = Highly suggestive of malignancy (≥95% probability). Immediate tissue biopsy (core needle biopsy preferred) is mandatory. BI-RADS 3 = probably benign (6-month follow-up). BI-RADS 4 = suspicious (biopsy recommended)."),

    ("29. Neoadjuvant chemotherapy (NACT) in breast cancer achieves pathological complete response (pCR). This is defined as:",
     ["A. >50% reduction in tumor size on imaging",
      "B. No residual invasive tumor in breast and axillary lymph nodes on pathological examination",
      "C. Complete normalization of tumor markers (CA15.3)",
      "D. No residual calcifications on post-treatment mammography"],
     "B",
     "pCR = absence of residual invasive carcinoma in the breast and lymph nodes (ypT0/is ypN0). It is a surrogate endpoint for improved event-free and overall survival, especially in TNBC and HER2+ subtypes."),

    ("30. A woman who has completed 5 years of tamoxifen for ER+ early breast cancer has significant residual risk. The MOST appropriate next step is:",
     ["A. Stop all therapy – 5 years is sufficient",
      "B. Switch to raloxifene",
      "C. Continue extended endocrine therapy (to 10 years) with tamoxifen or aromatase inhibitor",
      "D. Start CDK4/6 inhibitor"],
     "C",
     "Extended endocrine therapy (10 years total) reduces late recurrence in high-risk ER+ patients. ATLAS and aTTom trials showed benefit of extending tamoxifen to 10 years. Post-menopausal women can switch to aromatase inhibitor after 5 years of tamoxifen."),
]

for i, (q_text, options, correct, explanation) in enumerate(mcqs):
    story.append(Paragraph(q_text, q_style))
    for opt in options:
        story.append(Paragraph(opt, opt_style))
    story.append(Spacer(1, 0.1*cm))

story.append(PageBreak())

# ─── SECTION B: Short Answer Questions ───────────────────────────────────────
story.append(Paragraph("SECTION B: Short Answer Questions (4 marks each) — 20 marks", section_style))
story.append(HRFlowable(width="100%", thickness=0.5, color=TEAL))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph(
    "Answer any FIVE of the following questions. Write concisely (4–6 points per answer).",
    note_style))
story.append(Spacer(1, 0.3*cm))

saqs = [
    ("1. Describe the technique of clinical breast examination (CBE). What features on examination suggest malignancy?",
     ["Inspection in 4 positions: arms at side, arms raised, hands on hips, leaning forward",
      "Palpation: patient supine, arm behind head, use pads of 3 fingers, clock/concentric circle method",
      "Characterize lump: site, size, shape, surface, edge, consistency, mobility",
      "Axillary examination: support patient's arm, palpate all 5 node groups",
      "Features of malignancy: hard, irregular, ill-defined, tethered or fixed, axillary nodes, skin changes"]),
    ("2. What is Triple Assessment? How is each component scored and what does concordance mean?",
     ["Triple assessment = Clinical (C1–5) + Imaging (U1–5 / M1–5) + Tissue biopsy",
      "Score 1 = normal, 3 = uncertain, 5 = malignant in all arms",
      "Core needle biopsy preferred over FNAC (gives histology + receptor status)",
      "Concordance: all three arms agree → diagnosis confirmed",
      "Discordance: any disagreement → biopsy/re-biopsy required",
      "Combined diagnostic accuracy ~100% (Bailey and Love)"]),
    ("3. Classify breast carcinoma histologically and describe the features of invasive ductal carcinoma.",
     ["In situ: DCIS (ductal) and LCIS (lobular) – basement membrane intact",
      "Invasive: IDC/NST (75%), ILC (15%), mucinous, tubular, medullary, inflammatory",
      "IDC/NST: arises from TDLU, scirrhous growth, hard irregular mass",
      "ILC: Indian file pattern, multifocal, bilateral, often ER+",
      "Inflammatory carcinoma: T4d, dermal lymphatic emboli, worst prognosis"]),
    ("4. List the TNM staging of breast cancer and give the stage grouping for T2N1M0.",
     ["T: Tis (in situ), T1 ≤2cm, T2 2–5cm, T3 >5cm, T4 skin/chest wall",
      "N: N0 (none), N1 (mobile ipsilateral axillary), N2 (fixed/matted/IMN), N3 (supra/infraclavicular)",
      "M: M0 (no distant), M1 (distant metastases)",
      "T2 N1 M0 = Stage IIB",
      "T4 is always at least Stage IIIB; N3 = Stage IIIC; any M1 = Stage IV"]),
    ("5. What are the indications for breast-conserving surgery (BCS)? What treatment is MANDATORY after BCS?",
     ["Indications: tumor ≤4cm with favorable breast:tumor ratio, unifocal, patient preference",
      "BCS = lumpectomy with 2mm clear margins",
      "Contraindications: multicentric disease, prior RT to breast, T4 disease, patient refusal of RT",
      "MANDATORY after BCS: whole-breast radiotherapy",
      "BCS + RT = equivalent survival to mastectomy (NSABP B-06 trial)"]),
    ("6. Describe the molecular subtypes of breast cancer and their clinical relevance.",
     ["Luminal A (ER+/PR+/HER2–/low Ki67): best prognosis, hormone therapy only",
      "Luminal B (ER+/HER2–/high Ki67 OR HER2+): intermediate, may need chemo",
      "HER2-enriched (ER–/PR–/HER2+): aggressive, anti-HER2 therapy (trastuzumab)",
      "Triple Negative (ER–/PR–/HER2–): worst prognosis, chemo only, BRCA1-associated",
      "Clinical relevance: guides ALL systemic treatment decisions"]),
    ("7. What are the risk factors for breast cancer? Distinguish modifiable from non-modifiable factors.",
     ["Non-modifiable: age, female sex, BRCA1/2 mutation, family history, early menarche, late menopause, nulliparity",
      "Modifiable: obesity (post-menopausal), HRT (combined), alcohol, sedentary lifestyle, OCP",
      "Protective: breastfeeding, physical exercise, early first pregnancy",
      "BRCA1: chromosome 17; BRCA2: chromosome 13",
      "Lifetime risk with BRCA mutation: ~65–75%"]),
    ("8. How is sentinel lymph node biopsy (SLNB) performed? What are its advantages over ALND?",
     ["Technique: periareolar or peritumoral injection of blue dye ± Tc-99m radioisotope",
      "First draining node (sentinel) identified by blue staining or gamma probe",
      "Node removed and examined – frozen section or H&E",
      "If negative: no further axillary surgery; if positive: proceed to ALND",
      "Advantages over ALND: less lymphedema (< 3% vs 15–20%), less arm morbidity, shorter hospital stay",
      "Standard of care for clinically node-negative breast cancer"]),
]

for idx, (q_text, key_points) in enumerate(saqs):
    story.append(Paragraph(f"Q{idx+1}. {q_text}", q_style))
    # Answer lines
    for _ in range(5):
        story.append(HRFlowable(width="100%", thickness=0.3, color=colors.lightgrey))
        story.append(Spacer(1, 0.38*cm))
    story.append(Spacer(1, 0.2*cm))

story.append(PageBreak())

# ─── ANSWER KEY ──────────────────────────────────────────────────────────────
story.append(Paragraph("ANSWER KEY — FOR EXAMINER USE ONLY", 
    ParagraphStyle("ak", parent=styles["Heading1"], fontSize=16, textColor=RED, 
                   alignment=TA_CENTER, spaceAfter=4)))
story.append(HRFlowable(width="100%", thickness=2, color=NAVY))
story.append(Spacer(1, 0.3*cm))

# MCQ answer grid
story.append(Paragraph("Section A – MCQ Answers:", section_style))

ans_rows = []
row = []
for i, (_, __, correct, __) in enumerate(mcqs):
    row.append(f"Q{i+1}: {correct}")
    if len(row) == 5:
        ans_rows.append(row)
        row = []
if row:
    while len(row) < 5:
        row.append("")
    ans_rows.append(row)

ans_table = Table(ans_rows, colWidths=[3.4*cm]*5)
ans_table.setStyle(TableStyle([
    ("FONTNAME", (0,0), (-1,-1), "Helvetica-Bold"),
    ("FONTSIZE", (0,0), (-1,-1), 11),
    ("TEXTCOLOR", (0,0), (-1,-1), colors.HexColor("#006400")),
    ("BACKGROUND", (0,0), (-1,-1), colors.HexColor("#F0FFF0")),
    ("BOX", (0,0), (-1,-1), 0.5, colors.HexColor("#AAAAAA")),
    ("INNERGRID", (0,0), (-1,-1), 0.3, colors.HexColor("#CCCCCC")),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("ALIGN", (0,0), (-1,-1), "CENTER"),
]))
story.append(ans_table)
story.append(Spacer(1, 0.5*cm))

# Detailed explanations
story.append(Paragraph("Explanations:", section_style))
for i, (q_text, __, correct, explanation) in enumerate(mcqs):
    story.append(Paragraph(f"<b>Q{i+1} – Answer: {correct}</b>", ans_style))
    story.append(Paragraph(explanation, exp_style))

story.append(Spacer(1, 0.5*cm))
story.append(Paragraph("Section B – Short Answer Key Points:", section_style))
for idx, (q_text, key_points) in enumerate(saqs):
    story.append(Paragraph(f"<b>Q{idx+1}. {q_text}</b>", 
        ParagraphStyle("sqh", parent=q_style, fontSize=10, spaceAfter=2)))
    for pt in key_points:
        story.append(Paragraph(f"• {pt}", exp_style))
    story.append(Spacer(1, 0.15*cm))

# Footer
story.append(Spacer(1, 0.5*cm))
story.append(HRFlowable(width="100%", thickness=1, color=RED))
footer_style = ParagraphStyle("footer", parent=styles["Normal"],
    fontSize=8.5, textColor=DGRAY, alignment=TA_CENTER, italic=True)
story.append(Paragraph(
    "Sources: Bailey &amp; Love's Short Practice of Surgery 28th Ed. | Robbins &amp; Cotran Pathologic Basis of Disease 10th Ed. | "
    "Harrison's Principles of Internal Medicine 22nd Ed. | AJCC 8th Edition | NCCN Guidelines 2025",
    footer_style))

# ─── Build PDF ────────────────────────────────────────────────────────────────
doc.build(story)
print("Quiz PDF created successfully!")