Triple-Negative Breast Cancer (TNBC)

PATHCHAT Edition No. 33
Please contact your local Ampath pathologist for more information.

Author: Dr. Lerato Nokoane, MBChB (Natal), FC Path (SA) Anatomical

Introduction

🔹 Breast cancer is the most common cancer among women globally.

• Approximately 1.7 million new cases are diagnosed annually.
• In South Africa, the incidence is 40 per 100,000 people per year.
• Despite lower incidence rates in Africa, breast cancer mortality remains disproportionately high.

✅ Breast cancer classification combines:

1. Histomorphological features (tumour type, grade).
2. TNM staging (tumour size, lymph node involvement, metastases).
3. Molecular subtyping using gene expression analysis.

✅ Gene expression analysis identifies four main breast cancer subtypes:

• Luminal A (ER+/HER2-).
• Luminal B (ER+/HER2+).
• HER2-enriched (ER-/HER2+).
• Basal-like (triple-negative).

🔹 Triple-Negative Breast Cancer (TNBC) Defined:

• Lacks expression of oestrogen receptor (ER), progesterone receptor (PR), and HER2 protein.
• Diagnosis is confirmed via immunohistochemistry (IHC) and/or fluorescence in situ hybridisation (FISH) on formalin-fixed paraffin-embedded tissue.
• First recognized in the late 1990s following HER2 testing advancements.

📌 TNBC is aggressive and has fewer treatment options due to the absence of targeted hormone or HER2 therapies.

Clinicopathologic Features of TNBC

🔹 TNBC accounts for:

• 10–20% of all breast cancers.
• Up to 25% of high-grade breast tumours.

🔹 Demographic & Clinical Characteristics:

• More common in premenopausal women.
• Higher prevalence in women of African descent.
• Typically presents with larger tumour size (>5 cm).
• Exhibits pushing tumour borders with central necrosis.
• Prominent lymphocytic infiltration at the tumour periphery.

🔹 Histological Features:

• Solid sheets or nests of tumour cells.
• High nuclear grade and high mitotic rate.

📌 These aggressive features contribute to TNBC’s poor prognosis and high recurrence rates.

Prognosis of TNBC

✅ TNBC is associated with:

• Rapid tumour growth.
• Higher recurrence rates (within the first 3 years post-treatment).
• Increased likelihood of distant metastasis.

✅ Common Metastatic Sites:

• Brain.
• Lungs.
• Liver.
• Distant lymph nodes.

📌 TNBC lacks effective targeted therapies, making it more difficult to treat than other breast cancer subtypes.

Treatment of TNBC

🔹 TNBC does not respond to hormonal or HER2-targeted therapies.
✅ Current standard treatment:

• Systemic chemotherapy.
• Surgery (mastectomy or lumpectomy) for localized disease.
• Radiotherapy in high-risk cases.

🔹 Chemotherapy in TNBC:

• Platinum-based chemotherapy (cisplatin, carboplatin) shows promising results.
• Some TNBCs may be sensitive to PARP inhibitors (for BRCA-mutated cases).

📌 Despite chemotherapy responsiveness, TNBC patients often have worse outcomes compared to other breast cancer subtypes.

Conclusion

✅ TNBC is an aggressive breast cancer subtype with high recurrence rates and a lack of targeted treatment options.
✅ It disproportionately affects premenopausal women and those of African descent.
✅ Early detection and aggressive chemotherapy remain the best approach to management.

References

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