When Is Regional Nodal Radiation Warranted in Breast Cancer With Micrometastases?

At the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Jose Bazan, MD, discussed data examining practice patterns and factors associated with the use of regional nodal irradiation in patients with breast cancer and lymph node micrometastases. Multivariate analysis showed that involvement of more than one lymph node and larger tumor size—particularly tumors measuring 3 to 5 cm or greater than 5 cm—were significantly associated with receipt of regional nodal radiation, even after controlling for factors such as menopausal status and type of surgery. Bazan noted that these findings align with existing clinical practice, in which micrometastatic disease in a single lymph node is generally considered low risk, while multiple involved nodes raise greater concern.

Pharmacy Times: Only about 15% of patients received regional nodal irradiation—what factors seem to be driving clinicians toward radiation de-escalation in this population?

Jose Bazan, MD: Yeah, this is a really interesting finding, and it kind of confirmed what a lot of us do in practice. When I worked at Ohio State, we kind of came, before City of Hope, together as a group and decided who the patients with micrometastases were that we were going to consider offering more comprehensive treatment to, specifically after mastectomy. We had all agreed as a group, with no data, that more than one lymph node was the threshold.

When we think about micrometastases and this other entity that wasn’t part of the study called isolated tumor cells, these are small volumes of disease in lymph nodes. We think that’s a low-risk situation if it’s in one lymph node, but if it’s in more than one lymph node, that raises our level of concern.

On multivariate analysis from the study, only 84 patients received regional nodal radiation. But even when controlling for other factors, like menopausal status and type of surgery, having more than one involved lymph node was associated with receiving regional lymph node radiation. That confirmed what some of our practice already was. Another important factor was larger tumors, specifically tumors more than 5 centimeters or in the 3- to 5-centimeter range compared with smaller tumors, which also makes a lot of sense.

Pharmacy Times: Until results from TAILOR RT are available, how should real-world data like this influence shared decision-making and treatment planning?

Bazan: Another fantastic question. We hope to have outcomes data soon, but I will say that five-year outcomes data by type of radiotherapy received was already published a few years ago by Dr. Reshma Jagsi in JAMA Oncology. That analysis looked at the entire patient population and didn’t separate by macro- or micrometastases, but patients had extremely low rates of local and regional recurrence at five years. We’re going to have the 10-year data soon, and we expect the risks to be even lower in patients with micrometastases compared with macrometastases.

As long as that’s confirmed, the practice pattern data suggest that we can continue the way we approach things now, which is to de-escalate or omit regional nodal irradiation for the vast majority of patients. However, we need to be thoughtful about who we recommend regional nodal radiation for. By thoughtful, I mean looking not only at the number of lymph nodes involved and tumor size, but also at the location of the primary tumor in the breast.

When you have all this data, the vast majority of patients can undergo de-escalated approaches to radiotherapy. However, some patients are at higher risk. This cohort included hormone receptor–positive, HER2-negative breast cancers with Oncotype scores less than or equal to 25, but there may be patients with micrometastases who have triple-negative or HER2-positive breast cancer.

When higher-risk features are present, including subtype and other factors we identified, it’s important to have a discussion with the patient. That discussion should include the recommendation for more comprehensive radiation, acknowledgment that we don’t know how large the benefit will be, especially in light of excellent outcomes data, and a discussion of potential side effects and possible benefits, allowing patients to make an informed decision.

I don’t think there’s any data coming anytime soon, until we get TAILOR RT, which will mandate regional nodal irradiation. I’m hopeful that MA.39 will identify a subgroup of patients where we can further de-escalate radiation.