PA30.2 | Carcinoma of the Breast — Summary & Reflection

REFLECT

Now that you have worked through the full spectrum of breast carcinoma pathology, pause and consider this scenario:

A 35-year-old woman with a strong family history (mother and maternal aunt both had breast cancer before 50) is found to have a 1.8 cm Grade 3 invasive carcinoma on core biopsy. IHC: ER−/PR−/HER2−. Ki-67 is 75%.

Reflect on:
1. Which molecular subtype is this? What does this imply about her likely germline mutation status and what test would you recommend?
2. Using the Nottingham parameters: if tubule formation is <10% (score 3), nuclei are markedly pleomorphic (score 3), and mitoses are >10/HPF (score 3), what is the grade?
3. What are the two most important treatment options given the IHC findings — and why cannot standard targeted therapies (tamoxifen, trastuzumab) be used?
4. She asks whether her daughters are at risk. What is the lifetime risk of breast cancer for a BRCA1 mutation carrier, and what surveillance/preventive options would you counsel?

Discuss your answers with a peer or tutor before reviewing the summary block.

KEY TAKEAWAYS

Carcinoma of the Breast — Core Examination Points

Epidemiology & Risk:
• Most common female cancer worldwide; peak post-menopausal (median ~52 in India)
• Key risks: prolonged estrogen exposure, BRCA1 (chr 17, triple-negative), BRCA2 (chr 13, ER+), atypical hyperplasia, prior radiation

In Situ Carcinoma:
• DCIS: Malignant cells within ducts, basement membrane intact, myoepithelium present; comedo type (central necrosis, linear calcifications, HER2+) = highest risk of progression
• LCIS: Distended TDLUs, small discohesive cells, E-cadherin negative, bilateral risk marker, incidental finding

Invasive Carcinoma:
• IDC NST (70–80%): Hard/stellate/gritty, desmoplastic stroma, irregular nests and cords; variable IHC
• ILC (10–15%): Soft, no discrete mass, single-file pattern, E-cadherin negative, ER+, peritoneal/GI metastases
• Medullary: Syncytial high-grade + lymphoid stroma, triple-negative yet better prognosis; common in BRCA1
• Mucinous: Cells floating in mucin lakes, ER+, elderly women, excellent prognosis
• Tubular: Angulated tubules, no myoepithelium, Grade 1, ER+, excellent prognosis
• Inflammatory: Dermal lymphatic invasion + clinical syndrome = T4d, neoadjuvant chemo first
• Paget disease: Paget cells in nipple epidermis = always underlying carcinoma

Molecular Subtypes (IHC surrogates):
• Luminal A (ER+/PR+/HER2−/Ki-67 low) → best prognosis, endocrine only
• Luminal B (ER+, high Ki-67 or HER2+) → endocrine ± chemo ± anti-HER2
• HER2-enriched (ER−/HER2+) → trastuzumab + chemo
• Triple-negative (ER−/PR−/HER2−) → chemo; PARP inhibitors for BRCA+ TNBC

Grading (Nottingham): Tubules + Nuclear pleomorphism + Mitoses; each 1–3; total 3–5 = G1, 6–7 = G2, 8–9 = G3

Key Prognostic Factors: Axillary nodal status (most important), tumour size, grade, LVI, molecular subtype

Spread: Axillary nodes (most common lymphatic route) → internal mammary → supraclavicular; haematogenous to bone (most common distant site), lung, liver, brain