Insight

Jan 23, 2025, 13:55

Debate Highlights Presented by Prof. Hope Rugo: Should Chemotherapy Alone Be the Standard for Early-Stage TNBC?

During 17th Breast, Gynecological & Immuno-Oncology International Cancer Conference, Prof. Hope Rugo delivered a comprehensive argument focusing on the question of whether chemotherapy alone is sufficient for treating early-stage triple-negative breast cancer (TNBC), specifically for T1c node-negative disease.

Key Arguments Supporting Chemotherapy Alone

1. Efficacy in T1c TNBC:

Retrospective studies show excellent outcomes with chemotherapy alone in early-stage TNBC.
High breast cancer-specific survival rates (93–94%) observed, even in patients with residual disease after chemotherapy.

2. Heterogeneity in TNBC Subtypes:

TNBC encompasses a wide spectrum of biological behaviors.
Low-grade and high-TIL tumors often have favorable prognoses and may not benefit from escalation with immunotherapy.
Chemotherapy remains effective for proliferative, basal-like subtypes typically associated with higher risk.

3. Balancing Risk and Benefit:

Immune checkpoint inhibitors (ICIs) like pembrolizumab or atezolizumab can cause long-term toxicities, such as adrenal insufficiency, requiring lifelong management.
Chemotherapy has a lower long-term toxicity profile with established, manageable risks.

4. Current Guidelines:

No major guidelines (NCCN, ASCO, ESMO) recommend ICIs for T1c node-negative TNBC.
Chemotherapy remains the standard of care in this setting.

Supporting Evidence

KEYNOTE-522 Trial:
Most benefits with pembrolizumab were observed in node-positive or higher-stage disease.
T1c node-negative patients showed a small relative benefit with ICIs, not sufficient to justify routine use.
SEER Data (2010–2019):
T1c TNBC patients treated with chemotherapy showed excellent outcomes with event rates remaining very low.
High Tumor-Infiltrating Lymphocytes (TILs):
Retrospective studies highlight that patients with high TILs in T1c TNBC have outstanding outcomes without immunotherapy or even chemotherapy.
Ongoing trials are exploring de-escalation strategies for high-TIL tumors.

Concerns with Immunotherapy in Early TNBC

Toxicity Risks:
Lifelong adrenal insufficiency in up to 8% of cases with some ICI regimens.
Acute immune-related adverse events requiring lifelong management.
Uncertain Benefits in Low-Risk Disease:
Small absolute benefit in T1c TNBC.
Immunotherapy’s cost and side effects outweigh its potential advantages in this subset.

Conclusion by Prof. Hope Rugo

For true T1c node-negative TNBC, chemotherapy alone is highly effective and remains the standard of care.

Immunotherapy adds significant toxicity with minimal additional benefit for this low-risk population.
Future strategies should focus on smarter, individualized treatment based on tumor biology, TIL levels, and other predictive biomarkers.