BREAST DISORDERS — GYNECOLOGY

Mastalgia | Fibroadenoma | Carcinoma Breast

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1. MASTALGIA (Breast Pain)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

A. CAUSATIVE FACTORS

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B. ETIOPATHOGENESIS — CHART WITH ARROWS

CYCLIC MASTALGIA
─────────────────────────────────────────────────────────────────
Luteal phase
  ↓
↑ Estrogen + Progesterone
  ↓
↑ Fluid retention in breast stroma
  ↓
Ductal & acinar distension + epithelial proliferation
  ↓
Stretch of nerve endings / capsular pressure
  ↓
BILATERAL, PREMENSTRUAL BREAST PAIN
  (resolves with menstruation)

NON-CYCLIC MASTALGIA
─────────────────────────────────────────────────────────────────
Ductal ectasia / benign cysts / fibroadenoma / sclerosing adenosis
  ↓
Periductal inflammation / capsular stretch
  ↓
UNILATERAL, CONSTANT/INTERMITTENT PAIN

EXTRAMAMMARY MASTALGIA
─────────────────────────────────────────────────────────────────
Costochondritis / rib fracture / herpes zoster / muscle strain
  ↓
Referred pain perceived as breast pain
  ↓
PAIN NOT REPRODUCED BY BREAST PALPATION
  (reproduced by chest wall compression)

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C. CLINICAL FEATURES

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D. INVESTIGATIONS

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E. COMPLICATIONS

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F. MANAGEMENT

PHARMACOLOGICAL & NON-PHARMACOLOGICAL ALGORITHM

MASTALGIA CONFIRMED (malignancy excluded by exam + imaging)
              ↓
    ┌─────────────────────────────────┐
    │       FIRST LINE                │
    │  • Reassurance (benign nature)  │
    │  • Well-fitted supportive bra   │
    │    (sports bra, day + night)    │
    │  • Exercise (3×/week)           │
    │  • Pain diary                   │
    │  • Reduce dietary fat/caffeine  │
    └────────────┬────────────────────┘
                 │ No improvement (4–6 weeks)
                 ↓
    ┌─────────────────────────────────┐
    │       SECOND LINE               │
    │  • Topical NSAIDs (Diclofenac   │
    │    gel) — cyclic & non-cyclic   │
    │  • Oral NSAIDs (short course)   │
    │  • Evening Primrose Oil         │
    │    (γ-linolenic acid)           │
    └────────────┬────────────────────┘
                 │ No improvement
                 ↓
    ┌─────────────────────────────────────────────┐
    │       THIRD LINE — SERMs                    │
    │  • Tamoxifen 10–20 mg/day (most evidence)   │
    │  • Ormeloxifene 60 mg twice weekly          │
    │    (noncyclic mastalgia)                    │
    │  • Toremifene                               │
    └────────────┬────────────────────────────────┘
                 │ Severe / refractory
                 ↓
    ┌─────────────────────────────────────────────┐
    │       FOURTH LINE — Hormonal Modulators     │
    │  • Danazol 100–200 mg BD → taper to 100 mg  │
    │    [ONLY FDA-APPROVED drug for mastalgia]   │
    │    (SE: acne, hirsutism, weight gain,       │
    │     voice change, amenorrhoea)              │
    │  • Bromocriptine 2.5 mg BD                  │
    │    (SE: nausea, dizziness)                  │
    │  • GnRH agonists — rarely, severe cases     │
    └────────────┬────────────────────────────────┘
                 │
    ┌────────────▼────────────────────────────────┐
    │  If on OCP/HRT → DISCONTINUE first          │
    │  Treat underlying anxiety/depression        │
    └─────────────────────────────────────────────┘

Surgical management: Surgery is NOT a standard treatment for mastalgia. Local excision is occasionally considered for persistent localized non-cyclic mastalgia with an identifiable structural lesion (e.g., cyst, fibroadenoma) after all medical options are exhausted.

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2. FIBROADENOMA

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A. CAUSATIVE FACTORS

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B. ETIOPATHOGENESIS — CHART WITH ARROWS

PREDISPOSING FACTORS
(estrogen stimulation, MED12 / RARA mutations,
immunosuppression)
          ↓
Deranged transcriptional regulation
in intralobular stromal cells
          ↓
Proliferation of BOTH epithelial AND
stromal components of terminal duct lobular unit
          ↓
Well-circumscribed, encapsulated mass forms:
  ┌───────────────────────────────────────┐
  │  Pericanalicular pattern:             │
  │  stroma surrounds patent ducts        │
  │         OR                            │
  │  Intracanalicular pattern:            │
  │  stroma compresses ducts into         │
  │  cleft-like spaces                    │
  └───────────────────────────────────────┘
          ↓
Gross: rubbery, gray-white encapsulated nodule
       Bulges above surrounding tissue
Natural history:
  ├─ 15%: Spontaneous regression
  ├─ 75%: Stable (2–3 cm plateau)
  └─ 5–10%: Progressive growth

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C. CLINICAL FEATURES

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D. INVESTIGATIONS

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E. COMPLICATIONS

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F. MANAGEMENT

MANAGEMENT ALGORITHM

SUSPECTED FIBROADENOMA (young woman, firm mobile breast lump)
                    ↓
        TRIPLE ASSESSMENT
   Clinical + Imaging + FNAC/Biopsy
                    ↓
    ┌───────────────────────────────────────────────┐
    │         IMAGING CONFIRMS FIBROADENOMA         │
    └───────────┬──────────────────────┬────────────┘
                │                      │
         AGE <35 yrs                AGE ≥35 yrs
         Ultrasound                 Mammogram +
                                    Ultrasound
                ↓                      ↓
    ┌───────────────────┐   ┌──────────────────────┐
    │  CLASSIC IMAGING  │   │  ATYPICAL / GROWING  │
    │  + BENIGN FNAC    │   │  / SIZE >3 cm        │
    └────────┬──────────┘   └──────────┬───────────┘
             ↓                          ↓
    CONSERVATIVE MANAGEMENT      SURGICAL EXCISION
    • Reassurance                 (under local/general
    • Short-interval follow-up      anaesthesia)
      ultrasound at 6 months          ↓
    • Annual surveillance        Histopathology
    • Patient choice:                 ↓
      watch vs. excision       Rule out phyllodes
             ↓                  / carcinoma
    If growth or patient
    anxiety persists
             ↓
    ┌──────────────────────────────────────────┐
    │  MINIMALLY INVASIVE OPTIONS              │
    │  • US-guided vacuum-assisted biopsy      │
    │    (percutaneous excision)               │
    │  • Cryoablation (percutaneous)           │
    └──────────────────────────────────────────┘

Pharmacological Management

• No specific drug treatment for fibroadenoma
• If associated mastalgia: topical NSAIDs, danazol, tamoxifen (as per mastalgia protocol)
• Hormonal manipulation (stop OCP if multiple fibroadenomas and patient wishes)

Surgical Management

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3. CARCINOMA BREAST

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A. CAUSATIVE FACTORS (Risk Factors)

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B. ETIOPATHOGENESIS — CHART WITH ARROWS

GENETIC / ENVIRONMENTAL TRIGGERS
(BRCA1/2, TP53, PTEN mutations; radiation; carcinogens)
              ↓
DNA damage in terminal duct lobular unit epithelium
              ↓
Failure of DNA repair / apoptosis
(Loss of tumor suppressors: p53, Rb, PTEN)
              ↓
Oncogene activation (HER2, cyclin D1, MYC)
              ↓
Clonal proliferation — in situ phase:
  ┌────────────────────┬─────────────────────┐
  │   DCIS             │    LCIS             │
  │ (E-cadherin +)     │ (E-cadherin –)      │
  │ Ductal growth      │ Lobular growth      │
  │ Microcalcifications│ Incidental finding  │
  └────────┬───────────┴──────────┬──────────┘
           ↓                      ↓
    Basement membrane invasion
              ↓
INVASIVE CARCINOMA
  ┌───────────────────────────────────────────────────┐
  │  Invasive Ductal (NST) — 70–80%                   │
  │  Invasive Lobular — 10–15%                        │
  │  Special types: Mucinous, Tubular, Medullary, etc │
  └──────────────────────┬────────────────────────────┘
                         ↓
    Lymphovascular invasion
              ↓
    ┌─────────────────────────────────────┐
    │  Regional lymph node metastasis     │
    │  (Axillary → Supraclavicular)       │
    └──────────────┬──────────────────────┘
                   ↓
    Haematogenous spread → Bone, Lung, Liver, Brain

MOLECULAR SUBTYPES:
  Luminal A (ER+/PR+, HER2–, low grade) — best prognosis
  Luminal B (ER+, HER2+ or high grade)
  HER2-enriched (ER–/PR–, HER2+)
  Triple Negative (ER–/PR–/HER2–) — worst prognosis

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C. CLINICAL FEATURES

Early/Localized Disease

Advanced/Inflammatory Breast Cancer

Paget Disease of Nipple

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D. INVESTIGATIONS

Triple Assessment (Gold Standard)

TRIPLE ASSESSMENT
─────────────────────────────────────────────────────
1. CLINICAL EXAMINATION
   History + Physical (lump characteristics)

2. IMAGING
   ┌──────────────────────┬──────────────────────────┐
   │ <35 years            │ ≥35 years                │
   │ Ultrasound (1st)     │ Mammography (1st)        │
   │                      │ + Ultrasound (supplement)│
   └──────────────────────┴──────────────────────────┘
   MRI: Local staging, multifocal disease, BRCA carriers
   
3. TISSUE DIAGNOSIS
   • FNAC — Cytology (rapid)
   • Core needle biopsy — Histology + receptor status
     (ER, PR, HER2, Ki-67)
─────────────────────────────────────────────────────

Staging Investigations

TNM Staging (AJCC)

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E. COMPLICATIONS

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F. MANAGEMENT

PHARMACOLOGICAL MANAGEMENT

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SURGICAL MANAGEMENT

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COMPREHENSIVE MANAGEMENT ALGORITHM

NEWLY DIAGNOSED BREAST CARCINOMA
              ↓
    TRIPLE ASSESSMENT + STAGING
    (TNM, ER/PR/HER2, Ki-67, genomic testing)
              ↓
 ┌────────────────────────────────────────────────────┐
 │            STAGE 0 (DCIS)                         │
 │  Lumpectomy + Radiation ± Tamoxifen/AI × 5 yrs   │
 │  OR Total Mastectomy (large/multifocal DCIS)      │
 └────────────────────────────────────────────────────┘
              ↓
 ┌────────────────────────────────────────────────────┐
 │         EARLY STAGE (I–II)                        │
 │                                                    │
 │   BCS (Lumpectomy) + SLNB + Adjuvant RT           │
 │         = Modified Radical Mastectomy              │
 │        (equivalent survival — patient choice)      │
 │                                                    │
 │   AXILLA: SLNB → if positive → ALND               │
 │                                                    │
 │   ADJUVANT SYSTEMIC THERAPY:                       │
 │   ─────────────────────────────────────────────── │
 │   HR+ (ER/PR+):                                   │
 │     Tamoxifen (premenopausal) × 5–10 yrs          │
 │     AI (postmenopausal) × 5 yrs                   │
 │     If high risk: + Chemotherapy (AC-T)            │
 │                                                    │
 │   HER2+:                                          │
 │     Trastuzumab + Pertuzumab + Taxane chemo        │
 │                                                    │
 │   Triple Negative (ER–/PR–/HER2–):               │
 │     AC-T Chemotherapy                              │
 │     If node+/tumor>2cm: + Pembrolizumab           │
 └────────────────────────────────────────────────────┘
              ↓
 ┌────────────────────────────────────────────────────┐
 │      LOCALLY ADVANCED (IIIA–C)                    │
 │                                                    │
 │   NEOADJUVANT THERAPY FIRST:                       │
 │   (downstage to allow BCS or resection)            │
 │   • HR+: Neoadjuvant endocrine or chemo            │
 │   • HER2+: Neoadjuvant Trastuzumab + chemo        │
 │   • TNBC: Pembrolizumab + AC-T (neoadjuvant)      │
 │              ↓                                     │
 │   SURGERY (MRM or BCS if downstaged)              │
 │              ↓                                     │
 │   ADJUVANT RT + Systemic therapy                  │
 └────────────────────────────────────────────────────┘
              ↓
 ┌────────────────────────────────────────────────────┐
 │         METASTATIC (Stage IV)                      │
 │                                                    │
 │   Goal: Disease control, QOL, prolonged survival  │
 │                                                    │
 │   HR+/HER2–: CDK4/6 inhibitor + AI               │
 │               (Palbociclib/Ribociclib + Letrozole) │
 │   HER2+: Trastuzumab + Pertuzumab + Docetaxel     │
 │           → on progression: TDM-1 or Tucatinib    │
 │   TNBC: Pembrolizumab + chemo                     │
 │   BRCA1/2: PARP inhibitor (Olaparib)              │
 │   Bone mets: Zoledronic acid + RT                 │
 │   Brain mets: RT ± lapatinib/tucatinib (HER2+)    │
 └────────────────────────────────────────────────────┘

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COMPARATIVE SUMMARY TABLE

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Quick Navigation

1. Mastalgia — Causative factors, etiopathogenesis chart, clinical features, investigations, complications, management algorithm
2. Fibroadenoma — Causative factors, MED12/RARA pathogenesis chart, clinical features, triple assessment, complications, management algorithm
3. Carcinoma Breast — Risk factors, multi-step carcinogenesis chart (in-situ → invasive → metastatic), clinical features by stage, TNM staging, pharmacological table, surgical options, comprehensive treatment algorithm

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Key Highlights for Exam

MASTALGIA

• Cyclic (2/3 of cases): bilateral, premenstrual, 3rd–4th decade → estrogen-driven
• Non-cyclic (1/3): unilateral, constant/burning, 4th–5th decade → harder to treat
• Only FDA-approved drug: Danazol (synthetic androgen)
• First line: well-fitted bra + exercise + reassurance
• Second line: topical/oral NSAIDs
• Third line: Tamoxifen or Ormeloxifene (SERMs)
• Fourth line: Danazol → Bromocriptine

FIBROADENOMA

• Most common benign breast tumor; MED12 mutations in 2/3 of cases
• "Breast mouse" — firm, rubbery, freely mobile, non-tender
• 15% spontaneous regression; 5–10% grow; NOT a cancer precursor
• Management: observation if classic imaging + benign FNAC; excise if >3 cm, growing, or atypical
• Minimally invasive: vacuum-assisted biopsy or cryoablation

CARCINOMA BREAST

• BRCA1/2 → 50–85% lifetime risk (autosomal dominant)
• Triple assessment = Clinical + Imaging + Histology (core needle biopsy for receptor status)
• Molecular subtypes: Luminal A (best) → Triple Negative (worst prognosis)
• BCS + radiotherapy = MRM in survival terms (Stages I–II)
• Sentinel lymph node biopsy before axillary dissection
• Adjuvant: Tamoxifen (premenopausal ER+); Aromatase inhibitors (postmenopausal ER+); Trastuzumab (HER2+); Pembrolizumab + AC-T (TNBC)
• Metastatic HR+: CDK4/6 inhibitors (Palbociclib + Letrozole); BRCA mutated: PARP inhibitors (Olaparib)