Which Patients Are More Likely to Achieve a Pathological Response in Early Breast Cancer?

One of the questions we most often ask in clinical practice is: “Which patients receiving neoadjuvant systemic treatment achieve a pathological complete response (pCR) , with no invasive tumor detected in the surgical specimen?” To answer this more clearly, we systematically analyzed data compiled by our team's medical oncologist, Dr. Selami Bayram, and published our findings on 28 October 2025 in Current Oncology. I wanted to share a summary of our recent scientific paper here.

Summary at a Glance 📊

• Design: 2015–2023, single-center, retrospective; 200 patients with stage II–III disease
• Primary endpoint: pCR (ypT0/is ypN0)
• Overall pCR: 36%
• pCR by subtype: HER2-positive 65%, TNBC 56%
• Independent predictors of pCR: HER2 positivity (OR 4.21), Ki-67 > 47.5% (OR 3.62), ER < 10% (OR 2.77), radiological complete response–CR (OR 10.03)
• Follow-up: median 75 months
• pCR and recurrence risk: Among patients achieving pCR, recurrence risk was 84% lower (HR 0.16; p=0.014)
• 5-year DFS: pCR (%)91.5 vs non-pCR (%)72.8

Key Numbers (Summary Table)

What Does This Mean Clinically?

1. pCR is a strong “early signal.” Particularly in the HER2-positive and TNBC subtypes, it markedly improves 5-year recurrence-free survival (91.5% vs 72.8%).
2. Who Is More Likely to Achieve pCR? HER2 positivity, ER<10% and Ki-67>47.5% are independent markers. Radiological CR is the strongest predictor (OR≈10) and must be considered in surgical and axillary decisions.
3. Without pCR, the Road Map Is Clear. In TNBC, capecitabine and/or pembrolizumab; in HER2-positive disease, T-DM1; and in HR+/HER2-negative disease, long-term risk should be managed with endocrine ± CDK4/6 -focused approaches.

What the Numbers Tell Us

• OR 4.21 (HER2+): The relationship between biology and pCR is strong in clinical practice.
• Ki-67 Cutoff of 47.5%: Sensitivity of 0.82 offers the advantage of “not missing a pCR candidate”; specificity of 0.46 indicates the need for a composite model (subtype + ER + imaging + Ki-67).
• HR 0.16 (DFS): pCR reduces recurrence risk to approximately 1/6of the original level.

Limitations and Transparency ⚠️

• Retrospective, single-center; because of the study period (2015–2023), there was no neoadjuvant immunotherapyand limited platinum use.
• TIL, BRCA, RCB data were not systematically available; pathological response was assessed using Miller–Payne .

How Would I Apply This in Practice?

• Before NAST: HER2+, low-ER, high-Ki-67 profiles have a high probability of pCR; explain this clearly during counseling.
• Interim assessment: If radiological CR is present, individualize surgical/axillary strategies.
• After surgery: In non-pCR cases, systematically consider post-neoadjuvant escalation (T-DM1 / capecitabine / IO).
• Routine reporting: For Ki-67, 47.5% can be reported as a pragmatic cutoff; it should be interpreted within a combined modelrather than on its own.

Final Thoughts

This analysis shows that interpreting biology (HER2, ER, proliferation) and imaging response together is key to predicting pCR. In patients who do not achieve pCR, systematically using the opportunity for post-neoadjuvant intensification is critical to long-term benefit.