Endocrine therapy with accelerated Partial breast irradiatiOn or exclusive ultra-accelerated Partial breast irradiation for women aged ≥ 60 years with Early-stage breast cancer (EPOPE): The rationale for a GEC-ESTRO randomized phase III-controlled trial

Abstract

Breast cancer in the elderly has become a public health concern; there is a need to re-design its treatment with a view to de-escalation. Our paper sets out the rationale for a phase 3 randomized trial to evaluate less burdensome adjuvant procedures that remain effective and efficient. Materials and methods: For low-risk breast cancer in the elderly, adjuvant treatment has been adjusted in order to make it more suitable and efficient. Hypofractionated radiation therapy based on accelerated or non-accelerated regimens as well as accelerated and ultra-accelerated partial breast irradiation (APBI) protocols were reviewed. Withdrawal of radiation (RT) or endocrine therapies (ET) from the adjuvant procedure were also investigated. Based on molecular and APBI classifications, inclusion criteria were discussed. Results: Phase 3 randomized trials which compared standard vs. accelerated/non-accelerated hypofractionated regimens confirmed that the latter were non-inferior in terms of local control. Similarly, except for intraoperative-based techniques, APBI achieved non-inferior local control rates compared to whole breast irradiation for low-risk breast cancer. In phase 2 prospective trials using ultra APBI, encouraging results were observed regarding oncological outcome and toxicity profile. In phase 3 trials, adjuvant ET without RT significantly increased the rate of local relapse with no impact on overall survival while RT alone proved effective. Elderly patients aged 60 or more with low-risk, luminal A breast cancer were chosen as the target population in a phase 3 randomized trial comparing APBI + 5-year ET vs. uAPBI (16 Gy 1f) alone. Conclusion: To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

Ten-Year Results of Accelerated Partial-Breast Irradiation with Interstitial Multicatheter Brachytherapy after Breast-Conserving Surgery for Low-Risk Early Breast Cancer

“…Furthermore, ET is associated with limiting toxicity and a reduced quality of life in patients included in these randomized de-escalation trials [ 20 ]. Therefore, randomized trials are already ongoing not only to address the role of hormonal therapy vs. APBI regarding cancer control but also the quality of life [ 21 , 22 ].…”

Recent Advances in Optimizing Radiation Therapy Decisions in Early Invasive Breast Cancer

“…Equivalence of accelerated partial breast radiation delivered by external beam has been demonstrated in several clinical trials and endorsed for women with tumors with favorable biology, and together with ultra-hypofractionation, may be an attractive option in resource-restricted regions. Investigations for further de-intensifying radiation schedules using ultra-accelerated partial breast radiation as a single fraction are being planned to be tested against accelerated partial breast radiation + endocrine therapy [199,200].…”

Accelerated Partial Breast Irradiation

“…With respect to deintensification, the EUROPA trial is comparing RT alone to endocrine therapy alone 49. Likewise, the GEC-ESTRO Breast Cancer Working Group has conceived a phase III randomized trial using multicatheter interstitial brachytherapy, EPOPE, which is designed to test 30 to 32 Gy in 7 to 8 fractions versus 16 Gy in a single fraction, with the primary endpoint of disease-free survival 50. In addition, trials are evaluating shorter courses of PBI.…”

“…49 Likewise, the GEC-ESTRO Breast Cancer Working Group has conceived a phase III randomized trial using multicatheter interstitial brachytherapy, EPOPE, which is designed to test 30 to 32 Gy in 7 to 8 fractions versus 16 Gy in a single fraction, with the primary endpoint of disease-free survival. 50 In addition, trials are evaluating shorter courses of PBI. For example, initial outcomes from the TRI-UMPH-T trial demonstrated the safety and feasibility of a 3 fraction PBI approach with further outcomes expected in the years to come; in addition, advances in treatment technology have allowed for the evaluation of a single-fraction postoperative PBI approach.…”