Role of Radiation Continues to Evolve in Breast Cancer Treatment

He James Zhu, MD, PhD

The role of radiation therapy, specifically with elective nodal irradiation (ENI), has evolved over the past several years, said He James Zhu, MD, PhD, adding that the technique should be performed in patients with breast cancer on an individualized basis.

“[We need to be] educated about the role of ENI through regional lymph nodes, with the basic concept that radiation may improve survival or at least improve the locoregional control of disease, particularly in the setting of neoadjuvant chemotherapy,” said Zhu.

In an interview during the 2020 OncLive^® State of the Science Summit^™ on Breast Cancer, Zhu, a radiation oncologist at Tennessee Oncology, discussed the role of ENI in breast cancer and research efforts that may answer some remaining questions surrounding this modality.

OncLive: How has the role of ENI affected radiation therapy?

Zhu: Historically, the role of ENI has been in question. The trials [from Denmark and British Columbia] that have been published validate the disease-free survival and overall survival benefits of ENI combined with chest-wall irradiation for postmastectomy patients with node-positive breast cancer.

However, that has changed significantly in the past couple of decades as surgeons started to move away from upfront axillary nodal dissection which these trials were based on. Instead, sentinel nodal biopsy should be used. Furthermore, neoadjuvant chemotherapy is used more commonly.

Whether ENI is still relevant becomes an urgent question because we face this scenario every day in the clinic. As medical and surgical oncologists, our call is [to gain] perspective on whether any regional nodal irradiation may play a role in improving survival.

Could you expand on that from a radiologist’s perspective?

There are more questions than there are answers. However, some studies have shined a light in a particular direction. In general, ENI is helpful in certain scenarios, such as when a patient has undergone neoadjuvant chemotherapy and converted [patients from node-positive] disease to node-negative disease.

Still, certain populations may not benefit from ENI at that point. That was suggested by a pooled analysis of 2 National Surgical Adjuvant Breast and Bowel Project (NSABP) trials from the 1990s, which showed a locoregional recurrence rate of 0% in patients who had a pathologic complete response after neoadjuvant chemotherapy and mastectomy.

Currently, the randomized phase III NSABP-B-51 trial is trying to address whether the addition of regional nodal irradiation has a role in improving outcomes for patients.

What strategies are being utilized to mitigate adverse events associated with this treatment?

Historically, radiation oncologists shied away from radiating the regional lymph nodes for fear of added toxicities to the skin as well as to the intrathoracic organs like the lung, heart, and esophagus. In fact, ENI was not permitted in NSABP national trials until the late 1990s.

Of course, radiation therapy technology has evolved over the past few decades. We have respiratory gating and deep inspiration breath hold techniques. The patient can also be treated in prone position, with the breast tissue hanging farther away from the heart.

Of course, proton therapy has emerged as a potential solution for some of the most anatomically challenging cases.

Are any other trials important to mention?

NSABP-B-51 is the first trial we should pay close attention to. It is randomizing patients who have clinical N1 disease who are subsequently converted to N0 disease after neoadjuvant chemotherapy.

Patients are randomized into 2 groups based on the surgical management [they received]. Those who underwent lumpectomies will be randomized to breast radiation alone versus breast radiation plus ENI. Patients who underwent mastectomies will be randomized to chest-wall and regional lymph node radiation versus no radiation.

What are the remaining challenges with radiation in the breast cancer space?

Many grey zones exist with this topic. For example, what about T3 breast cancer or radiographically detected lymph nodes that turned out to be metastatic [via biopsy]? All sentinel lymph node biopsy trials enrolled patients based on these criteria alone; there was no palpable adenopathy.

Historically, our imaging technique was not as good [as it is now]. In all trials, the number of large, primary tumor breast cancer cases was near 0, and T3 tumors were underrepresented.

We are scratching our heads when presented with a patient in that scenario. In addition to pathologic information, such as the tumor grade, we look at whether patients have presence of lymphovascular invasion, [whether they] are premenopausal, and what their hormone receptor status is. Now, with the genetic analysis around the corner, more questions will need to be answered.

What is your take-home message?

Close collaboration among 3 branches of oncology—surgical, medical, and radiation—is the key. We are intertwining our advances in each specialty more and more. How does the surgeon performing a sentinel lymph node biopsy influence the decisions of the medical and radiation oncology team? Similarly, how does the neoadjuvant chemotherapy given to the patient by the medical oncologist influence the decision of the surgeon or radiologist? Early communication is key.