Meta-analysis reveals pathological complete response benefits from neoadjuvant immuno-chemotherapy combination in patients with HER2-negative breast cancer

Purpose This meta-analysis aims to evaluate the pooled pathological complete response (pCR) rate and the relative benefits across different subgroups in human epidermal growth factor receptor 2 (HER2) -negative breast cancer treated with immunotherapy. Methods Clinical trials for neoadjuvant immunotherapy in combination with chemotherapy were identified. The pooled pCR rate of total population and patients across different subgroups was performed. Results Totally, the meta-analysis included 15 clinical trials comprising 3,885 patients. The pooled pCR rate was 58% (95% CI, 54–62) for triple-negative breast cancer (TNBC) patients and 25% (95% CI, 22–27) for hormone receptor (HR)-positive/HER2-negative (HR+HER2-) patients, respectively. However, the relative benefit of neoadjuvant chemotherapy combined with immunotherapy compared to chemotherapy was comparable ( p = 0.70), with odds ratio (OR) of 1.76 (95% CI, 1.43–2.17) in TNBC patients and 1.87 (95% CI, 1.49–2.36) in HR+HER2- patients. Subgroup analysis showed that programmed cell death ligand-1 (PD-L1)-positive patients had higher pCR benefits compared to PD-L1-negative patients, regardless of whether it was immunotherapy combined with neoadjuvant chemotherapy or neoadjuvant chemotherapy alone, with OR of 3.41 (2.61–4.45) and 2.48 (1.80–3.42) respectively. Conversely, among patients receiving chemotherapy alone, the pCR rate in lymph node-positive cases was 42% lower than that in lymph node-negative cases, while the addition of immunotherapy enabled lymph node-positive patients to achieve a comparable pCR rate to lymph node-negative patients (OR, 1.08). Conclusion Immunotherapy showed substantial benefits in improving pCR rates in both TNBC and HR+HER2- patients when combined with neoadjuvant chemotherapy, especially in lymph node-positive breast cancer patients.