Oncology

Breast Cancer

The most common cancer in women. Receptor status — ER, PR, HER2 — is the single most important piece of information on the biopsy report. Get that right and the treatment algorithm falls into place.
Ready Updated Jun 2026
Invasive ductal carcinoma H&E ×40
IDC — H&E ×40. Irregular infiltrating glands, nuclear pleomorphism.
00 Overview

Snapshot

~2.3 million new cases per year worldwide — it's not rare, it's the most common cancer in women. About 70% are hormone receptor-positive, meaning they depend on oestrogen to grow. Catch it at Stage I and over 95% of patients survive 5 years. Miss it until Stage IV and that number drops to 28%. The practical message: screen early, biopsy definitively, and always check the receptor status before touching treatment.

#1
Cancer in women worldwide
~70%
Hormone receptor-positive
>95%
5-yr survival if Stage I
~28%
5-yr survival if Stage IV
01 Classification

Molecular Subtypes

Breast cancer is not one disease. The four molecular subtypes behave completely differently — different prognosis, different treatment. The subtype is defined by three immunohistochemistry markers: ER, PR, HER2. Know these cards cold.

Luminal A
~40% · Most common
Markers ER+/PR+, HER2−, Ki-67 low
Behaviour Slow-growing, indolent
Tx Endocrine therapy ± chemo
Prognosis Best of the four
Luminal B
~20% · Still HR-positive
Markers ER+/PR+, HER2± or Ki-67 high
Behaviour More proliferative than A
Tx Endocrine + chemo ± trastuzumab
Prognosis Intermediate
HER2-enriched
~15% · Historically aggressive
Markers HER2+, ER−/PR−
Behaviour Fast-growing; transformed by targeted Tx
Tx Trastuzumab + pertuzumab + chemo
Prognosis Intermediate (dramatically improved)
Triple-Negative (TNBC)
~15% · Hardest to treat
Markers ER−, PR−, HER2−
Behaviour Aggressive; no hormonal/HER2 target
Tx Chemo ± pembrolizumab; PARP-i if BRCA+
Prognosis Worst — no targeted options
Mechanism — ER/PR+ pathway & where drugs act
Aromatase Androgen → Oestrogen ✕ Aromatase inhibitors E2 ER receptor ✕ Tamoxifen (SERM) E2-ER complex Nucleus ERE binding → gene transcription Cell Proliferation (ovary · adipose · adrenal) Post-menopause: adipose is the main E2 source Use tamoxifen Use AI (post-meno)
Mechanism — HER2 pathway & where drugs act
Cell membrane HER2 amplified kinase domain HER1/3 dimerize Trastuzumab blocks HER2 RAS / RAF / MEK / ERK ↑ Cell proliferation PI3K / AKT / mTOR ↓ Apoptosis, ↑ survival Key facts · HER2 amplified in ~25% of breast cancers · Historically: worst prognosis · Trastuzumab (Herceptin) transformed outcomes completely · Also: pertuzumab, T-DM1, T-DXd · Check HER2 by IHC + FISH if 2+ · Cardiotoxicity: baseline echo required
02 Clinical

Clinical Presentation

Most breast cancers are found on routine screening — the patient feels completely well. When symptoms do appear, think in terms of what the tumour is doing to nearby structures.

  • Painless lump — firm, irregular, poorly mobile. Upper outer quadrant (UOQ) most common. Pain is a late or unusual feature.
  • Skin dimpling — Cooper's ligaments tethered by the tumour. Pathognomonic when present.
  • Peau d'orange — orange-peel texture from dermal lymphatic blockage. Suggests locally advanced disease.
  • Nipple changes — retraction, bloody/serous discharge, inversion in a previously normal nipple.
  • Paget's disease — eczematous, crusting nipple rash. Always underlying DCIS or invasive cancer. Biopsy the nipple, don't treat as eczema.
  • Inflammatory breast cancer — diffuse erythema, warmth, rapid onset, no fever. Looks like mastitis but isn't. Core biopsy urgently.
  • Axillary nodes — hard, fixed ipsilateral nodes suggest nodal spread.
Mammography showing breast cancer
Mammography: spiculated high-density mass with irregular margins — classic malignant appearance. Note the architectural distortion around the lesion.Wikimedia Commons
Board Tip

A young woman presents with a red, swollen breast unresponsive to antibiotics. Think inflammatory breast cancer, not mastitis. The key differentiator: inflammatory BC has no fever, no leukocytosis, and doesn't improve with antibiotics. Punch biopsy of the skin is the next step.

03 Workup

Diagnostics & Staging

①
Clinical exam
History, inspection, palpation
②
Imaging
Mammogram ± ultrasound
③
Biopsy
Core needle — mandatory

All three are required. A positive clinical exam alone or positive mammogram alone is not enough to treat. You need tissue.

  • MammographyFirst-line imaging. Look for: spiculated mass, microcalcifications (DCIS), architectural distortion, asymmetry.
  • UltrasoundFor dense breasts, women <35, axillary nodes. Distinguishes solid vs cystic. Guides biopsy.
  • Core needle biopsyGold standard. Gives histology + grade + ER/PR/HER2/Ki-67. Must be done before any treatment decision.
  • MRI breastHigh-risk surveillance (BRCA+), lobular cancer extent assessment, pre-op planning. Not routine.
  • Staging CT + bone scanFor Stage III–IV or symptoms (bone pain, cough, dyspnoea, neurological). PET-CT increasingly preferred.
Gross pathology of breast cancer
Gross pathology: firm, stellate, grey-white tumour with irregular infiltrating borders — typical IDC macroscopic appearance.Wikimedia Commons

TNM Staging & Survival

StageDescription5-yr SurvivalPrognosis
0DCIS — non-invasive, confined to ducts~99%Excellent
ITumour ≤2 cm, node-negative>95%Excellent
IITumour 2–5 cm or 1–3 positive nodes~86%Good
IIILarge tumour, ≥4 nodes, skin/chest wall involvement~57%Fair
IVDistant metastases — bone, lung, liver, brain~28%Poor
04 Treatment

Management

Treatment is multimodal and always subtype-driven. The biopsy report — especially ER, PR, HER2, and Ki-67 — determines the systemic therapy before surgery is even discussed. The sequence below applies to early-stage (I–III) disease.

Treatment sequence — early breast cancer
①
Biopsy
ER · PR · HER2 · Ki-67 · Grade
②
±Neo-adjuvant
Chemo/targeted before surgery (HER2+, TNBC, Stage III)
③
Surgery
BCS or mastectomy + sentinel node biopsy
④
Adjuvant
Systemic therapy based on receptor status
⑤
Surveillance
Annual mammogram + clinic review × 5–10 yr
Systemic therapy — by receptor status
Core Biopsy Result Check ER · PR · HER2 · Ki-67 ER+ / PR+ · HER2− Luminal A / B ENDOCRINE THERAPY Pre-meno: Tamoxifen (SERM) × 5–10 yr Post-meno: AI (anastrozole, letrozole, exemestane) High-risk/mets: + CDK4/6 inhibitor (palbociclib / ribociclib) ± Chemotherapy (if high-grade or Ki-67 high) HER2+ (any HR) HER2-enriched / Luminal B ANTI-HER2 + CHEMO Trastuzumab (Herceptin) + Pertuzumab (Perjeta) + Chemotherapy (taxane) Duration: 1 year total ⚠ Cardiotoxic — echo before & during Residual disease post-neo-adj: → T-DM1 (ado-trastuzumab) If HR+: add endocrine therapy ER− · PR− · HER2− Triple-Negative (TNBC) CHEMOTHERAPY ± IMM. Backbone: AC → Taxane (anthracycline + taxane) PD-L1+ (CPS ≥10): + Pembrolizumab BRCA1/2 mutated: + Olaparib (PARP-i) adjuvant after chemo ± Carboplatin (BRCA+) ALL SUBTYPES Surgery (BCS or mastectomy) + Radiotherapy (after BCS, or post-mastectomy if high-risk)
Surgery — choosing the approach
BCS + Radiotherapy ✓ Preferred
Breast-Conserving Surgery
  • Survival equivalent to mastectomy for Stage I–II — offer this first
  • Radiotherapy is mandatory post-BCS — reduces recurrence by ~50%
  • Requires clear surgical margins (≥1 mm)
  • Not suitable if: multifocal, large tumour-to-breast ratio, prior chest RT
Mastectomy — When indicated
Total / Modified Radical
  • Large tumour (>5 cm) or poor tumour-to-breast ratio
  • Multifocal or multicentric disease
  • BRCA1/2 carrier — prophylactic contralateral mastectomy discussable
  • Patient preference after fully informed consent
Axilla — Sentinel Node First
Lymph Node Management
  • SLNB — sentinel lymph node biopsy for all clinically N0 patients. Avoids full dissection + morbidity.
  • ALND — axillary lymph node dissection if ≥3 positive sentinel nodes or clinically N+
  • Lymphoedema risk rises significantly with ALND — avoid unless necessary
Radiotherapy — Indications
When to Irradiate
  • Always after BCS — whole breast RT is standard of care
  • Post-mastectomy if: T3/T4, ≥4 positive nodes, close/positive margins
  • Regional nodal RT if axillary, internal mammary, or supraclavicular nodes involved
Stage IV / Metastatic disease

Metastatic breast cancer is not curable with current treatments — the goal is disease control, symptom management, and quality of life. That said, modern targeted therapies have transformed median survival from ~18 months to several years in HR+ and HER2+ disease.

ER+ / HER2−
CDK4/6 inhibitor era
CDK4/6-i + AI is first-line standard.
Palbociclib, ribociclib, abemaciclib.
Doubles PFS vs AI alone.
HER2+
ADC revolution
Trastuzumab deruxtecan (T-DXd) is transforming outcomes. Also active in HER2-low.
Pertuzumab + trastu 1st line.
TNBC / Bone mets
Supportive + targeted
TNBC: sacituzumab govitecan (ADC).
Bone mets: denosumab or bisphosphonates to prevent skeletal events.
05 High-yield

Clinical Pearls

Triple assessment is non-negotiable. Clinical + imaging + biopsy. Each one alone has a meaningful false-negative rate. You need all three before you can reassure a patient that a lump is benign.
Peau d'orange ≠ infection. When you see it in a breast that isn't getting better with antibiotics, that's inflammatory breast cancer until proven otherwise. Core biopsy of the skin. Don't wait.
Tamoxifen is an agonist in the uterus. It blocks oestrogen in breast tissue (good), but stimulates the endometrium (bad). Prolonged use → increased endometrial cancer risk. Annual gynaecological review in patients on long-term tamoxifen.
AIs only work post-menopausally (or when ovarian function is suppressed). Their mechanism is blocking aromatase — the main extra-gonadal source of oestrogen in post-menopausal women. Pre-menopausally, the ovaries dominate and AIs alone are insufficient.
BRCA1 → TNBC. BRCA2 → ER+ luminal. This association matters because it affects genetic counselling, surveillance, prophylactic surgery decisions, and treatment (PARP inhibitors for BRCA+ TNBC).
HER2: always confirm with FISH if IHC 2+. IHC 2+ is equivocal — FISH confirms true amplification. Getting this wrong means either withholding trastuzumab (undertreating) or giving it unnecessarily (cardiotoxicity risk).
Check echo before trastuzumab. Anti-HER2 therapies are cardiotoxic — they can cause asymptomatic LV dysfunction or overt heart failure. Baseline LVEF is mandatory, with repeat monitoring throughout treatment.
High-grade IDC histology
High-grade IDC — marked nuclear pleomorphism, prominent nucleoli. Features of a poorly differentiated (Grade 3) tumour: aggressive behaviour, more likely TNBC or HER2+.Wikimedia Commons
Test yourself — Active Recall
Quiz questions for this topic coming soon.