De-escalation of regional nodal management for breast cancer patients after primary systemic therapy: from radiation oncologist’s perspectives

Article information

Radiat Oncol J. 2025;43(1):1-3

Publication date (electronic) : 2025 March 18

doi : https://doi.org/10.3857/roj.2025.00108

Yong Bae Kim^,

Department of Radiation Oncology, Heavy Ion Therapy Research Institute, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, Seoul, Republic of Korea

Correspondence: Yong Bae Kim Department of Radiation Oncology, Heavy Ion Therapy Research Institute, Yonsei Cancer Center, Yonsei University Health System, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea Tel: +82-2-2228-8095 E-mail: ybkim3@yuhs.ac

Received 2025 February 27; Revised 2025 March 6; Accepted 2025 March 10.

Breast cancer has increasingly been recognized as a systemic disease, leading to the understanding that if positive axillary disease is confirmed at diagnosis, primary systemic therapy should be prioritized, even when the tumor volume is small. The advent of targeted agents for the human epidermal growth factor receptor 2–positive type and the introduction of pembrolizumab in triple-negative breast cancer have significantly increased the rates of pathologic complete response [1,2]. Following surgery after neoadjuvant systemic therapy (NAST) when regional lymph node metastasis is confirmed at diagnosis, various scenarios may arise depending on the initial diagnosis, surgical interventions, and pathological findings.

A crucial issue is the administration of radiation therapy (RT). The results of the NRG Oncology/NSABP B-51/RTOG 1304 study were presented at the 2023 San Antonio Breast Cancer Symposium, indicating no significant difference in 5-year invasive breast cancer recurrence-free interval between the no regional nodal irradiation (RNI) and RNI groups after a follow-up of 59.5 months. Although further follow-up is warranted, if these results are confirmed, they are expected to establish Level 1 evidence that will be incorporated into routine clinical practice guidelines.

A consensus is yet to be reached regarding axillary management options such as axillary lymph node dissection (ALND), targeted axillary dissection, or axillary RT, and it will take considerable clinical experience to establish clear guidelines. However, in cases where ypN1 or higher is observed postoperatively, there seems to be a consensus on the necessity of RT, regardless of the surgical technique or number of lymph nodes involved. Current guidelines primarily recommend postmastectomy RT for patients with persistent axillary nodal involvement after NAST, as specified in the 2016 American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology guideline update [3].

Variability and uncertainty surrounding the RT exist, particularly in the two aforementioned scenarios. Moderate hypofractionation of the RNI has been established as the standard treatment in standard guidelines, suggesting a more uniform approach in this domain [4]. However, various delivery methodologies exist, ranging from anatomical landmark-based field delivery to anatomy-based delivery, all of which are used in real-world practice. The selected method inherently influences the policies surrounding volume coverage. The international European Breast Cancer Research Association of Surgical Trialists survey, in a recent issue of the Radiation Oncology Journal, reflected remarkable variability in responses regarding volume management [5].

Presently, the prevailing trend in breast cancer treatment is the optimization of therapy through de-escalation strategies, which will ultimately reflect on both surgical and RT approaches, gradually shifting towards de-escalation. Our understanding suggests that as research data and real-world experiences accumulate, a distinct preference will develop for sentinel lymph node dissection (SLND) over ALND. Similarly, RNI practices adapt to reflect a reduction in volume for optimization.

In scenarios in which a disease-free status is confirmed after ALND or SLND, emerging evidence suggests that RNI may soon be safely omitted from oncological practice. Conversely, various opinions arise as to whether axillary residual disease is detected post-ALND or SLND. Generally, if ypN2 or higher residual disease is noted post-ALND, the implementation of a wide RNI is deemed necessary. However, more nuanced discussions exist concerning ypN1, in which the necessity of RT may depend on the number of nodes removed and the lymph nodes involved, resulting in a range of opinions regarding the extensive application of RNI. As classifications lean towards N1mic or N0(+i), the inclination to limit or omit RT coverage may increase. For cases with post-SLND–positive disease, there may be a tendency to select a broader RNI when adding RT as opposed to relying on ALND, yet some advocate for implementing a limited RNI in line with the ACOSOG Z0011 findings.

De-escalation of RT volume requires robust anatomical treatment planning, which is crucial for high-precision therapy. This entails advanced anatomical contouring and intensity-modulated radiation therapy (IMRT) planning. Although IMRT has been used for a long time in breast cancer treatment, oncologists have been hesitant to adoption because of concerns about the lack of supporting evidence, despite clear dosimetric advantages. The high costs associated with demonstrating the utility of treatment techniques through clinical trials, particularly for RT, which lacks substantial backing entities compared to chemotherapy, pose significant barriers to achieving Level 1 evidence.

Currently, the execution of IMRT depends on adequate resources, including equipment and personnel. The severe workload of radiation oncologists presents a notable hurdle, with IMRT demanding exponentially greater execution compared to that in 2-dimensional and 3-dimensional conformal technique. Defining not only the target but also the organs at risk, along with establishing planning goals and conducting quality assurance processes, requires substantial time commitments. Auto-contouring systems under development may alleviate some of this burden and auto-planning processes are likely to find their way into real-world applications.

Ultimately, de-escalation of both surgery and RT seeks to minimize toxicity and improve the quality of life, addressing issues such as lymphedema, which significantly affects daily living [6]. Minimizing the RT fields and employing high-precision therapies should guide treatment strategies to reduce complications without compromising efficacy. The increased use of breast reconstruction with implants following mastectomy is noteworthy, particularly because RT is known to correlate with a heightened risk of reconstructive complications such as capsular contracture [7]. Therefore, the oncological safety of omitting RT may be a pivotal factor in reducing adverse outcomes.

In conclusion, the optimal use of RT, including dosage and field, is still debated due to differing pathological results after NAST and surgical intervention. As we align with the de-escalation trend, adjustments in RT practices are also expected to evolve. However, the processes involved in optimizing the treatment could contribute to rising costs. Therefore, radiation oncologists should judiciously determine appropriate treatment policies, taking the available equipment and workforce resources into account. This balance is essential to ensure quality patient care while effectively managing economic considerations.