Editor's Note: For most patients, postoperative radiotherapy plays a crucial role. Some early-stage breast cancer patients require prophylactic regional lymph node irradiation (RNI) in addition to whole-breast irradiation (WBI). However, the survival benefit of RNI for patients with 1-3 positive axillary lymph nodes (pN1) remains uncertain. Therefore, it's necessary to evaluate the impact of RNI on the prognosis of pN1 breast cancer patients receiving systemic therapy. At the 2024 ASCO Conference, Korean researchers initiated the KROG 1701 study (Abstract 577) to explore this issue. "Oncology Frontier" invited Professor Yanxia Zhao from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, to interpret and comment on this study.

Study Overview

A Phase III Study Comparing Whole Breast Irradiation Plus Regional Lymph Node Irradiation to Whole Breast Irradiation Alone in Post-BCS pN1 Breast Cancer Patients Receiving Adjuvant Taxane Chemotherapy (KROG 1701)

Background: Whole-breast irradiation (WBI) following breast-conserving surgery (BCS) can reduce local recurrence and improve survival in breast cancer patients. Some early-stage breast cancer patients require prophylactic regional lymph node irradiation (RNI) in addition to WBI. For patients with ≥4 positive axillary lymph nodes (ALN), RNI is considered the standard treatment. However, the survival benefit of RNI for patients with 1-3 positive ALNs (pN1) remains uncertain. Previous randomized trials have shown significant improvement in disease-free survival (DFS) with RNI in pN1 breast cancer patients. However, only a small proportion of patients in these trials received modern systemic therapies proven to enhance local-regional control, such as taxanes or HER2-targeted therapies. The observed benefit of RNI might have been due to the suboptimal systemic treatments used in those studies. Therefore, it’s essential to evaluate the impact of RNI on the prognosis of pN1 breast cancer patients receiving modern systemic therapies. This study aims to compare the effects of WBI and WBI plus RNI on post-BCS pN1 breast cancer patients receiving adjuvant taxane chemotherapy.

Methods: KROG 17-01 (NCT03269981) is a prospective, multicenter, non-inferiority study that randomized post-BCS pN1 breast cancer patients who received taxane-based adjuvant chemotherapy to either WBI or WBI plus RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. Patient-reported outcomes (PROs) were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. PROs were compared between treatment groups using a linear mixed model.

Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received the assigned intervention, and 750 completed baseline PRO questionnaires (387 in the WBI+RNI group and 363 in the WBI group). Overall, PROs improved over time (P<0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (P<0.05) compared to the WBI group, with lower overall health status (P=0.090) and physical functioning (P=0.049), which were clinically significant. At 3-6 months post-RT, the WBI+RNI group also showed higher arm symptom scores (P=0.030). Aside from these specific time points, there were no significant differences in other PRO scores between the treatment groups, including arm and breast symptoms. Moreover, different RT techniques and fractionation methods did not significantly affect PROs, except for breast symptoms during RT.

Conclusions: In pN1 breast cancer patients receiving taxane-based chemotherapy, adding RNI was associated with slight, transient declines in specific PROs. However, these results were not statistically significant.

Expert Commentary

For most patients undergoing BCS, postoperative adjuvant radiotherapy (PORT) is crucial. Several randomized trials and meta-analyses have demonstrated that PORT after BCS reduces breast cancer recurrence and mortality. Systemic therapy is another critical component of breast cancer treatment and has seen significant advancements in recent years. Adding taxanes to adjuvant chemotherapy improves patient survival. However, since the primary clinical trials supporting PORT did not account for these advancements, the impact of modern systemic therapies on the effectiveness of radiotherapy remains uncertain. With the increasing use of systemic therapies, de-escalating certain aspects of PORT, such as narrowing the treatment field, might be feasible in some patients. If the oncological safety of de-escalated PORT can be confirmed, breast cancer patients might benefit from reduced toxicity, time, and healthcare costs.

The KROG 17-01 study, which included BCS patients receiving taxane-based adjuvant chemotherapy, primarily covered the axillary, supraclavicular, and internal mammary node regions in the RNI field. The study provides important information for PORT in pN1 breast cancer patients: RNI may be exempted for post-BCS pN1 breast cancer patients who have received taxane-based chemotherapy.