Radiotherapy De-Escalation in Younger Patients with Breast Cancer: Are We There Yet?

Background/Objectives: Radiotherapy de-escalation is an established strategy in the management of early breast cancer, supported by randomized evidence predominantly derived from older patient populations. Younger women remain underrepresented in de-escalation trials, despite exhibiting less favorable clinicopathological characteristics associated with increased locoregional recurrence and inferior survival. The objective of this systematic review is to assess the available evidence regarding the safety and implementation of radiotherapy de-escalation strategies in younger patients with early breast cancer. Methods: A literature search following the PRISMA 2020 guidelines was performed to identify studies evaluating radiotherapy de-escalation strategies in younger breast cancer patients. Ongoing and recently completed trials were identified through ClinicalTrials.gov. Epidemiological data, randomized trials, and current clinical guidelines were reviewed. Results: Younger age at diagnosis is consistently associated with more aggressive tumor biology, higher rates of nodal involvement, unfavorable molecular subtypes, and worse survival outcomes. Among de-escalation approaches, moderate hypofractionation (15–16 fractions) is supported by randomized evidence and contemporary guidelines and can be applied irrespective of age. In contrast, evidence supporting ultra-hypofractionation, partial breast irradiation, and omission of radiotherapy in younger patients remains less robust, as these strategies have largely been evaluated in older or postmenopausal populations. Conclusions: Radiotherapy de-escalation in younger patients with breast cancer should be approached with caution. While moderate hypofractionation appears safe regardless of age, more aggressive de-escalation strategies lack adequate evidence in women under 50 years, particularly those under 40. Further prospective studies with sufficient representation of younger patients are required to clarify the role of radiotherapy de-escalation in this population.