KEY TAKEAWAYS
- The study aimed to explore if on-treatment biopsies could predict pCR and DFS in invasive BC.
- The results showed that on-treatment biopsies can identify patients unlikely to achieve pCR, aiding therapy adjustments.
Patients who achieve a pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) tend to have better outcomes, including improved disease-free survival (DFS). Predicting early treatment response can be crucial in adapting therapies and reducing unnecessary surgical and systemic treatments.
On-treatment biopsies may provide an opportunity to assess treatment effectiveness before completion of therapy, especially in specific subtypes like triple-negative breast cancer (TNBC) and HER2-positive BC.
Bruno Valentin Sinn and the team aimed to investigate if on-treatment biopsies could predict pCR and assess their correlation with tumor-infiltrating lymphocytes (TILs), Ki-67 levels, and residual cancer presence.
The study involved 297 patients with invasive BC enrolled in 3 randomized, prospective neoadjuvant trials that were GeparQuattro, GeparQuinto, and GeparSixto. Participants had biopsies taken during treatment, and the amount of residual cancer, TILs, and the proliferation marker Ki-67 were compared to pre-treatment samples.
Researchers assessed the relationship between these factors and their impact on achieving pCR and DFS. Tumor subtypes included HR+/human epidermal growth factor receptor 2-negative (HER2-), TNBC, and HER2-positive.
Among the 297 samples, 138 (46%) were hormone receptor-positive (HR+)/human epidermal growth factor 2-negative (HER2-), 87 (29%) were TNBC, and 72 (24%) were HER2-positive.
Invasive tumor cells were detected in 70% of on-treatment biopsies, with varying rates across subtypes (HR+/HER2-: 84%, TNBC: 62%, HER2+: 51%; P< 0.001). Patients with residual tumor during treatment had an 8% pCR rate post-treatment (HR+/HER2-: 3%, TNBC: 19%, HER2+: 11%), while those without any invasive tumor achieved a 50% pCR rate (HR+/HER2-: 27%; TNBC: 48%, HER2+: 66%).
The sensitivity for predicting residual disease was 0.81, with positive and negative predictive values of 0.92 and 0.50, respectively. Increasing TILs from baseline to on-treatment biopsy (if residual tumor was present) were associated with a higher likelihood of achieving pCR in the overall cohort (OR 1.034, 95% CI 1.013-1.056 per % increase; P= 0.001) and a longer DFS in TNBC (HR 0.980, 95% CI 0.963-0.997 per % increase; P= 0.026). Persisting or increased Ki-67 levels were linked to a lower probability of pCR in the overall cohort (OR 0.957, 95% CI 0.928-0.986; P= 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001-1.047; P= 0.04).
The study concluded that on-treatment biopsies can help predict patients unlikely to achieve pCR, which could enable therapy adjustments for TNBC and HER2-positive BC.
These biopsies may also offer insights into mechanisms of treatment resistance. Future research should focus on refining the accuracy of on-treatment biopsy procedures and expanding their use in clinical practice.
Open Access funding enabled and organized by Projekt DEAL. This analysis was funded by GBG. The GeparQuattro trial received funding support from Roche and Sanofi-Aventis, GlaxoSmithKline, Novartis, Roche, Sanofi Aventis, and Cephalon.
Source: https://pubmed.ncbi.nlm.nih.gov/39317942/
Sinn BV, Sychra K, Untch M, et al. (2024). “On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.” Breast Cancer Res. 2024;26(1):138. Published 2024 Sep 24. doi:10.1186/s13058-024-01883-w
