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

## TL;DR

This paper reviews whether reducing radiotherapy is safe for younger breast cancer patients, finding that only moderate reductions are supported by evidence.

## Contribution

The paper systematically reviews the evidence for radiotherapy de-escalation in younger breast cancer patients, highlighting gaps in current data.

## Key findings

- Moderate hypofractionation is supported by evidence and can be safely applied regardless of age.
- Ultra-hypofractionation and partial breast irradiation lack strong evidence in younger patients.
- Younger patients have more aggressive tumors and higher recurrence risks, complicating de-escalation.

## Abstract

Radiotherapy de-escalation is an important approach in the management of early breast cancer, with the goal of limiting treatment burden, without compromising oncologic outcomes. However, implementation of such strategies in younger patients remains precarious, not only due to their underrepresentation in relative studies but also due to the more aggressive tumor biology, higher recurrence risk and worse survival observed in younger individuals. This review summarizes existing data on radiotherapy de-escalation strategies specifically in younger women with early breast cancer. The evidence supports that moderate radiotherapy hypo-fractionation can be safely applicated irrespective of age, as opposed to ultra-hypofractionation, partial breast irradiation and omission of radiotherapy, for which data remain uncertain. Future trials with adequate representation of younger patients are required to clarify the safety and applicability of de-escalation approaches to this particular population.

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.