Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer.
(2026) Cell Reports Medicine — Vol. 2026, n° 2026, p. 102544 (2026)
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- The NeoPAL trial compares neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk, early luminal breast cancer. At surgery, the NanoString BC360 proliferation score and Ki67 expression are reduced in both arms, together with upregulation of immune-related signatures. Overall, there is very little difference in the changes observed with LP as compared to CT, even in signatures related to response to estrogen and CDK4/6 manipulation. Deconvolution of bulk RNA sequencing (RNA-seq) data reveals high content at baseline in cancer cells, immunosuppressive cancer-associated fibroblasts, FOXP3+ CD4 regulatory T lymphocytes, and TREM2+ macrophages. In contrast, myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages, and SELL+ CD4 T lymphocytes accumulate after treatment in both arms. A low ROR score is observed at surgery in 63.3% and 43.5% of patients in the LP and CT arms, respectively. No 3-year breast cancer-specific survival events are observed in these patients. These data provide a rationale for CT-sparing trials in this setting.
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Cottu, P., Kieffer, Y., Lemonnier, J., D’hondt, V., Duhoux, F., Callens, C., Gentien, D., Reyes, C., Boulai, A., Desmoulins, I., Mouret-Reynier, M.-A., Levy, C., Heudel, P.-E., Dalenc, F., Grenier, J., Fuhrmann, L., Baulande, S., Delaloge, S., Mechta-Grigoriou, F., & Vincent-Salomon, A. (2026). Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer. Cell Reports Medicine, 2026(2026), 102544. https://doi.org/10.1016/j.xcrm.2025.102544 (Original work published 2026)