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🎓 BREAST CANCER — DETAILED HoPI FOR SEMINAR

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1. EPIDEMIOLOGY

• Most common non-skin malignancy in women worldwide — ~2.25 million new cases/year globally; ~290,000/year in the U.S.; ~43,000 deaths/year
• Lifetime cumulative incidence: 12.9% in women
• 75% of cases occur in women >50 years old
• Males represent <1% of cases but present at more advanced stages
• Incidence declining due to reduced HRT use, mammographic screening, and adjuvant therapies

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2. RISK FACTORS (Box 68.1 — Sabiston)

Demographic & Lifestyle

Hormonal Exposure

• Early menarche (<11 yrs), late menopause (>55 yrs) → prolonged estrogen exposure
• Nulliparity, first pregnancy after age 30, lack of breastfeeding
• Combined E+P HRT significantly increases risk; estrogen-only does NOT
• Ongoing oral contraceptive use

Genetic / Family History

• ~20% have family history; first-degree relative with premenopausal BC = significant risk
• BRCA1/BRCA2 mutations → 50–85% lifetime risk; autosomal dominant
• TP53 (Li-Fraumeni), PTEN (Cowden), PALB2, CHEK2, ATM
• 5–8% of breast cancers are hereditary; Ashkenazi Jewish background = higher BRCA1/2 prevalence

Histologic Risk Factors

Environmental

• Chest wall ionizing radiation in adolescence (e.g., Hodgkin lymphoma treatment)

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3. PATHOLOGY

In Situ Lesions

Invasive Types

1. IDC/NST (~75%) — most common; haphazard glandular invasion
2. ILC — "Indian-file" single-cell pattern; E-cadherin negative
3. Tubular — well-differentiated; best prognosis
4. Mucinous/Colloid — tumor cells in mucin lakes; good prognosis
5. Medullary — undifferentiated, lymphocytic infiltrate; BRCA1-associated
6. Paget disease — DCIS extending into nipple skin; eczematous nipple

Molecular Subtypes

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4. CLINICAL PRESENTATION — HoPI CORE

Presenting Complaint

Systematic HoPI Questions

🔵 The Lump

• Site: Which breast? Which quadrant? (Most common: upper outer quadrant, ~50%)
• Onset & Duration: When noticed? How?
• Character: Hard vs. soft; irregular vs. smooth; mobile vs. fixed to skin or deep tissue
• Size: Estimated size; has it changed?
• Malignant features: Hard, irregular, non-tender, fixed, with ill-defined margins

🔵 Skin Changes

• Dimpling / tethering: Cooper's ligament involvement
• Peau d'orange (orange-peel skin): Lymphatic blockage; hallmark of Inflammatory Breast Cancer (IBC)
• Skin ulceration / satellite nodules: T4b disease
• Erythema, warmth: IBC — must distinguish from mastitis (no response to antibiotics)
• Nipple retraction: Tumor traction or periductal fibrosis

🔵 Nipple Discharge

• Bloody / serosanguineous → most suspicious for malignancy
• Milky → galactorrhoea (prolactinoma)
• Green/yellow → duct ectasia
• Unilateral > bilateral (more concerning)

🔵 Nipple Changes

• Paget's disease: Unilateral eczematous, scaly, crusted nipple ± palpable mass; biopsy mandatory

🔵 Pain

• Breast cancer is typically painless in early stages — pain is more a feature of benign disease
• Ask about bone pain (back, hips, ribs) → bone metastases (most common metastatic site)

🔵 Axillary / Nodal Disease

• Palpable axillary lumps: Mobile or fixed? Matted? Number?
• Arm swelling (lymphoedema) or arm pain
• Supraclavicular nodes → N3 disease (stage IIIC)

🔵 Metastatic Symptoms (Systems Review)

🔵 Constitutional Symptoms

• Unintentional weight loss, fatigue, anorexia, night sweats

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5. PAST HISTORY

• Prior breast lumps, biopsies, atypical hyperplasia, LCIS
• Previous breast cancer (ipsilateral or contralateral)
• Prior chest wall radiation

6. GYNAECOLOGICAL HISTORY

• Age at menarche, parity, age at first delivery, breastfeeding
• Menopausal status and age at menopause
• HRT use (type: combined vs. estrogen-only; duration)
• Oral contraceptive use

7. FAMILY HISTORY

• Breast cancer in 1st-degree relatives — age at diagnosis
• Ovarian cancer (BRCA1/2 syndrome)
• Bilateral breast cancer in relatives
• Male relatives with breast cancer (BRCA2)
• Li-Fraumeni features (sarcomas, adrenal tumors in young relatives)

8. SOCIAL HISTORY

• Alcohol, smoking, obesity, physical activity
• Occupation (night shift)
• Psychological impact, support system

9. DRUG HISTORY

• HRT, OCPs, tamoxifen, aromatase inhibitors
• Prior chemotherapy
• Allergies (particularly contrast/iodine)

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10. INVESTIGATIONS

Triple Assessment

1. Clinical examination (history + physical)
2. Radiological: Mammogram ± Ultrasound ± MRI
3. Pathological: Core Needle Biopsy (CNB) — preferred over FNAC

Biomarkers (on CNB)

Bloods

• FBC, LFTs, serum calcium, ALP, tumour markers (CA 15-3, CEA)

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11. STAGING — AJCC 8th Edition TNM

T (Tumour)

• Tis: DCIS | T1: ≤20 mm | T2: 20–50 mm | T3: >50 mm | T4d: Inflammatory BC

N (Nodes — Pathologic)

• pN0: None | pN1: 1–3 axillary nodes | pN2: 4–9 nodes | pN3: ≥10 nodes / supraclavicular

Stage Groups

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12. MANAGEMENT OVERVIEW

Surgery

• BCS + Radiotherapy = equivalent survival to mastectomy (Stages I–II); proven in NSABP B-06, Milan I trial
• SLNB: For clinically node-negative patients
• ALND: For palpable or extensively involved nodes
• Mastectomy: Multifocal, large tumor, prior RT, patient preference; reconstruction offered

Radiotherapy

• Post-BCS: Reduces local recurrence from ~40% → <10%
• Post-mastectomy: For ≥4 positive nodes, T3/T4, positive margins

Systemic Therapy

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13. DIFFERENTIAL DIAGNOSIS

• Fibroadenoma (young, mobile, non-tender)
• Simple cyst (smooth, transilluminates)
• Fibrocystic change (cyclic pain, bilateral)
• Mastitis / breast abscess (lactating, febrile, responds to antibiotics)
• Inflammatory BC (mimics mastitis but antibiotic-resistant)
• Duct ectasia, fat necrosis, phyllodes tumor

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14. SAMPLE CASE HoPI TEMPLATE

"Mrs. [X], a [age]-year-old [pre/post]menopausal female, presented with a [duration] history of a painless, hard, irregular lump in the [right/left] [upper outer/other] quadrant of the breast, first noticed on [self-examination / mammogram / incidentally]. The lump is approximately [size] cm, hard in consistency, with ill-defined irregular margins, and appears fixed to the underlying tissue. She also reports [nipple retraction / skin dimpling / axillary swelling / nipple discharge — describe]. She denies features of metastatic disease including bone pain, dyspnoea, jaundice, or neurological symptoms. She has [no / significant] weight loss.

Risk factors: menarche at age [X], G[]P[], first delivery at age [X], [breastfed/not]. Menopause at [age]. She [has/has not] used combined HRT for [duration]. Family history: [details — mother/sister with BC; BRCA status if known]."

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• Goldman-Cecil Medicine, Chapter 183 — Breast Cancer
• Harrison's Principles of Internal Medicine 22E, Chapter 84
• Sabiston Textbook of Surgery, Chapter 68
• Robbins & Cotran Pathologic Basis of Disease, Chapter 23
• Mulholland & Greenfield's Surgery, Chapter 74
• AJCC Cancer Staging Manual, 8th Edition (2017)