Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects

SIMPLE SUMMARY: For breast cancer patients who do not wish to undergo any form of surgery, various non-surgical treatments have been investigated. Radiotherapy is considered the most important modality, but conventional radiotherapy alone or concurrent chemoradiotherapy do not lead to high local control rates. So, to increase curability, radiosensitization strategies, including the use of hydrogen peroxide injection before radiation and hyperthermia plus oral tegafur-gimeracil-oteracil potassium (S-1), have been investigated. These strategies have yielded promising outcomes, with local control rates of ~97%. A trial of carbon ion radiotherapy is ongoing, and particle therapy should be further investigated in the future. Image-guided ablation therapy including radiofrequency ablation and focused ultrasound have been investigated; although complete ablation rates of ≥70% have been reported, combination with radiotherapy may be necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily and will become a valuable treatment option for patients who refuse surgery. ABSTRACT: This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75–97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0–I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20–100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes.