Francesca Fede, Thomas Tessonnier, Domenico Ivan Filosa, Emilia Formicola, Valerio Cosimo Elia, Yasmin Hamad, Filipa Baltazar, Natalia Sycheva, Domenica Capasso, Line Hoeltgen, Eva Meixner, Amir Abdollahi, Lorenzo Manti, Ivana Dokic, Andrea Mairani
These findings suggest particle therapy as a promising strategy for aggressive BC, with p and 4He ions demonstrating particular potential. Importantly, 4He ions emerge as a distinctive intermediate option between protons and heavier ions, combining physical precision, biological efficacy, and clinical applicability.
PURPOSE: Breast cancer (BC) remains the most commonly diagnosed malignancy among women worldwide with an overall 5-year-survival rate of ∼90%. The prognosis worsens dramatically for patients with metastatic and/or aggressive subtypes. In such cases, particle therapy emerges as a promising approach, offering superior tumor control while limiting the risk of secondary pathologies.
METHODS AND MATERIALS: The radiobiological effects of X-rays were compared with those of protons (p), 4He and 12C ions, delivered using therapeutically-realistic Spread-Out Bragg Peaks, on 2D- and 3D-models of MDA-MB-231 (Triple-Negative (TN)) and MCF7 (ER-positive) BC cells, whereas 16O ions were used on the MDA-MB-231 cells. To achieve relevant insights, we evaluated conventional clonogenic survival and spheroid growth dynamics, mimicking tumor architecture, on both cell lines. Cell migration and invasion, tumor‑supernatant-induced angiogenesis and the expression of pro‑angiogenic factors were systematically investigated in the TN-BC subtype to assess the potential therapeutic advantages of ion-irradiation in aggressive BC models. The here-obtained in vitro data served as input for a comparative treatment planning study with p, 4He and 12C ions on ten TN-BC cases.
RESULTS: All ions exhibited superior efficacy compared to X-ray and effectively counteracted the X-ray-induced increase in migration and invasion. 4He ions indicated a unique balance of advantages, showing greater relative biological effectiveness and inhibition of spheroid growth than p, and a reduction in migration and invasion comparable to 12C ions. In the planning and NTCP study for TN-BC (α/β=9.4Gy), with similar OAR objectives (α/β=3Gy), p and 4He ions achieved comparable CTV coverage and OARs sparing, whereas 12C exhibited reduced coverage mainly due to this large α/β difference.
CONCLUSIONS: These findings suggest particle therapy as a promising strategy for aggressive BC, with p and 4He ions demonstrating particular potential. Importantly, 4He ions emerge as a distinctive intermediate option between protons and heavier ions, combining physical precision, biological efficacy, and clinical applicability.