Breast cancer Study Guide

📖 Core Concepts Breast cancer = malignant tumor arising from breast ducts (ductal) or lobules (lobular). Molecular subtypes are defined by estrogen‑receptor (ER), progesterone‑receptor (PR), and HER2 status → Luminal A/B, HER2‑enriched, Triple‑negative. TNM staging: T =size/extent of primary tumor, N = regional nodal involvement, M = distant metastasis; combined with grade & receptor status to form stage I‑IV. Screening: annual (or biennial) mammography; dense breasts ↓ sensitivity → supplemental US/MRI. Risk hierarchy: genetic predisposition (BRCA1/2, PALB2, TP53, PTEN) > prolonged estrogen exposure > lifestyle factors (alcohol, obesity, inactivity). Treatment pillars for localized disease: surgery + radiation + systemic therapy (chemo, endocrine, HER2‑targeted). Metastatic disease is managed mainly with systemic agents; local therapies are palliative. --- 📌 Must Remember Incidence: 25 % of female cancers; >100× more common in women than men. ER‑positive ≈ 70 % of cases; HER2‑positive ≈ 15‑20 %; Triple‑negative ≈ 15 %. BRCA1/2 → 70 % lifetime breast‑cancer risk, 33 % ovarian risk. Mammography detection: 90 % in fatty breasts, 60 % in extremely dense breasts. BI‑RADS 4/5 = suspicious → biopsy. Tumor grade: sum of tubule formation, nuclear pleomorphism, mitoses → 1 (3‑5), 2 (6‑7), 3 (8‑9). Stage I 5‑yr survival ≈ 100 %; Stage IV ≈ 33 %. HER2‑targeted adjuvant: trastuzumab 12 mo (± pertuzumab). Endocrine therapy duration: ≥5 yr (often up to 10 yr). Chemoprevention: tamoxifen/raloxifene ↓ incidence; aromatase inhibitors may be more effective. --- 🔄 Key Processes Screening → Diagnostic Work‑up Annual mammogram → if abnormal (BI‑RADS 0/4/5) → diagnostic mammogram + targeted US → core‑needle biopsy (or FNA for cystic lesions). Staging (TNM) Determine T size (T1 ≤2 cm, T2 2‑5 cm, T3 >5 cm, T4 invasion). Assess N (N0‑N3 based on nodal level/extent). Check M (M0 vs M1). Combine with grade & receptor status → overall stage. Adjuvant Therapy Decision Tree Node‑negative, low‑grade, ER+/HER2‑ → surgery + endocrine ± radiation. Node‑positive or high‑grade → add chemotherapy. HER2‑positive → add trastuzumab ± pertuzumab. Triple‑negative → chemo (no targeted endocrine/HER2). Metastatic Management HR‑positive → endocrine ± CDK4/6 inhibitor → add PI3K/mTOR inhibitors if progression. HER2‑positive → dual HER2 blockade (trastuzumab + pertuzumab) ± chemo; consider T‑DM1, T‑DXd, TKIs. Triple‑negative → chemo; add atezolizumab if PD‑L1+, pembrolizumab if DNA‑repair deficient. --- 🔍 Key Comparisons Mammography vs. Ultrasound Mammography: best for fatty breasts, detects calcifications; limited in dense tissue. Ultrasound: complements mammography, ideal for dense breasts & cystic vs solid evaluation. ER‑positive vs. Triple‑negative ER‑positive: hormone‑driven, responds to endocrine therapy, better prognosis. Triple‑negative: no ER/PR/HER2, limited targeted options, poorer survival, higher early recurrence. BRCA1 vs. BRCA2 BRCA1: higher association with triple‑negative tumors, earlier onset. BRCA2: more often ER‑positive, similar overall risk magnitude. Adjuvant Chemotherapy vs. Endocrine Therapy Chemo: cytotoxic, needed for high‑risk (node‑positive, high grade, HER2‑positive). Endocrine: cytostatic, used when tumors are hormone‑receptor‑positive, lower toxicity. --- ⚠️ Common Misunderstandings “Dense breasts increase cancer risk” – density lowers mammographic sensitivity but is not an independent risk factor in the outline. “Estrogen‑only HRT raises breast cancer risk” – it does not increase risk; it raises endometrial cancer risk. “All BRCA carriers need mastectomy” – prophylactic mastectomy reduces risk >95 % but is optional; surveillance with MRI is also acceptable. “Triple‑negative means no treatment options” – chemotherapy remains effective; immunotherapy approved for PD‑L1‑positive cases. --- 🧠 Mental Models / Intuition “The 3‑R model” for therapy selection: Receptor status → Risk (stage/grade) → Recommend appropriate systemic therapy. “Size‑Node‑Metastasis” ladder – visualize tumor progression as climbing steps: larger T → more nodes → distant M → each step drastically lowers survival. “Hormone exposure clock” – each year of unopposed estrogen (early menarche → late menopause) adds a tick toward higher risk. --- 🚩 Exceptions & Edge Cases Women <40 yr with BRCA mutation – start annual MRI at age 25, mammography added at 30. Pregnant patient – avoid ionizing radiation; use US first, MRI (no gadolinium) after 1st trimester; surgery in 2nd trimester; anthracycline chemo safe after 14 weeks. Male breast cancer – 90 % ER‑positive; treat with tamoxifen endocrine therapy. Inflammatory breast cancer – rapid swelling/redness; staged as T4 regardless of size; requires multimodal therapy (chemo + surgery + radiation). --- 📍 When to Use Which Screening: annual mammography 40‑49 (shared decision) → 50‑74 (routine). Add MRI/US for dense breasts or high‑risk. Biopsy: core‑needle for solid masses; vacuum‑assisted for microcalcifications; FNA for cystic fluid. Systemic therapy: HR‑positive → endocrine ± CDK4/6 (metastatic) or chemo if high risk. HER2‑positive → trastuzumab (+pertuzumab) ± chemo; consider T‑DM1 after progression. TNBC → neoadjuvant/ adjuvant chemo; add atezolizumab if PD‑L1+. Radiation: after lumpectomy (whole‑breast + boost for high grade); post‑mastectomy for T4 or ≥4 positive nodes. --- 👀 Patterns to Recognize Lump characteristics → hard, irregular, non‑painful = higher malignancy suspicion. Skin changes (dimpling, peau d’orange) → suggest dermal involvement (T4). Nipple discharge → consider intraductal pathology; bloody or unilateral warrants imaging. Dense breast + negative mammogram → think “masked lesion” → order supplemental US/MRI. High‑grade tumor + HER2‑positive → anticipate need for dual HER2 blockade plus chemotherapy. --- 🗂️ Exam Traps “Estrogen‑only HRT doubles breast cancer risk.” – Wrong; combined estrogen‑progesterone therapy doubles risk; estrogen‑only does not increase breast cancer risk. “BI‑RADS 3 always requires biopsy.” – Incorrect; BI‑RADS 3 is probably benign → short‑interval follow‑up, not immediate biopsy. “All patients with a family history need genetic testing.” – Not every family history qualifies; testing is indicated when ≥10 % hereditary risk (e.g., first‑degree relative with early‑onset disease). “Dense breast tissue is a contraindication for mammography.” – False; mammography is still performed; density just reduces sensitivity. “Triple‑negative tumors are HER2‑negative by definition.” – True, but remember they also lack ER/PR; some may express basal markers not covered here. ---