NSABP B-51 Data Highlight Evolving Role of Radiation in Early-Stage Breast Cancer

Bruce G. Haffty, MD, MS

Radiation therapy has historically been a cornerstone in the treatment of breast cancer, particularly for patients experiencing lymph node involvement. However, for patients whose positive lymph nodes convert to negative status following surgery, should radiation therapy be maintained?

In a presentation at the 23rd Annual International Congress on the Future of Breast Cancer^® East, Bruce G. Haffty, MD, MS, presented considerations surrounding the omission of radiation therapy in patients with node-positive breast cancer converted to node negative after neoadjuvant chemotherapy.

Findings from the phase 3 NRG/NSABP B-51/RTOG 1304 trial (NCT01872975) presented at the 2023 San Antonio Breast Cancer Symposium showed that at a median follow-up of 59.5 months, the estimated 5-year invasive breast cancer recurrence-free survival rate was 92.7% in patients who received regional nodal irradiation vs 91.8% in patients who did not (HR, 0.88; 95% CI, 0.60-1.29; P = .51).

“The study [data] demonstrated that patients whose lymph nodes converted to negative status had excellent outcomes with low [recurrence] events, regardless of whether they received regional nodal radiation,” Haffty explained in an interview with OncLive^®.

In the interview, Haffty delved into the clinical implications of data from NSABP B-51 and explained why further data could better help identify subgroups of patients where regional nodal radiation could have a role.

Haffty is the associate vice chancellor of Cancer Programs at Rutgers Biomedical Health Sciences of Rutgers Cancer Institute of New Jersey, and professor and chairman of Radiation Oncology at Rutgers-Robert Wood Johnson Medical School in New Brunswick.

OncLive: How have results from the NSABP B-51 trial affected clinical practice?

Haffty: This was a clinically impactful study that has already changed practice, even before the publication [of the full data]. This was based on the presentation of findings at the 2023 San Antonio Breast Cancer Symposium. Throughout the radiation oncology community, [findings from] this study have influenced the majority of [clinicians] to change how they [are treating patients with breast cancer whose disease converts to node-negative status].

The reason why the study is so important is that there was huge variability in practice based on arguments on both sides of the fence as to what the right thing to do was [for patients who converted to node-negative disease. [Decisions were based on] personal biases, professional institutional biases, and the like. [Treatment patterns] were all over the map.

In a patient who has negative lymph nodes, typically, we don't treat the regional lymph nodes. However, the question was, if they originally had positive lymph nodes and then became negative, should you treat them like they had positive lymph nodes or negative lymph nodes? That is why this trial was necessary to do.

What was the design of the study?

The study took patients who had somewhat advanced breast cancer, in that they had a positive lymph node; they had to have T1 to T3 [disease], meaning the primary tumor in the breast would be up to approximately 5 cm. They had to have a node that was pathologically positive.

Patients received chemotherapy, and usually, patients who [receive] chemotherapy will respond, as they did. If their lymph node converted to a negative lymph node from positive lymph node, then they were randomly assigned. If they had a lumpectomy, they were randomly assigned to either breast radiation or breast radiation plus regional nodal irradiation. If the [patient] had a mastectomy, they were randomly assigned to no radiation or radiation to the chest wall and regional lymph nodes.

These patients did extremely well. If you were a patient who had a positive lymph node and that lymph node converted to a negative lymph node [after chemotherapy], you did extremely well. There were a low number of [recurrence] events. The results were the same [regardless of] whether you had regional nodal radiation.

Some [clinicians] are waiting for the full publication [of the data] to learn a little bit more [about NSABP B-51]; however, [these results] have already influenced practice. The majority of radiation oncologists are probably now looking at patients and if they convert to node-negative [disease], [they] do not treat the lymph nodes.

Like any clinical trial, questions are raised [after data are reported]. The trial [findings] do not say that every patient who converts to node negative doesn't need regional nodal radiation. There are a few questions that [still] need to be answered. The trial investigators did a subgroup analysis, and there was no group that benefited from regional nodal radiation. There was a suggestion that patients with estrogen receptor [ER]–positive, HER2-negative breast cancer seemed to benefit a [small amount] from the radiation; however, we need further follow-up to digest data from that group. For patients with ER-positive, HER2-negative disease, and the patient is young, some [may] argue that regional radiation did some good [in this subgroup].

There are some other questions. If there is a lot of residual disease in the breast or extensive vascular invasion, you might still treat those patients [with regional nodal radiation]. Not every patient, but the vast majority of patients who convert to node-negative status would not need further treatment. There are some subsets where [regional nodal radiation] might still be necessary. In the future, longer follow-up and further analysis [will be important]. For the most part, most radiation oncologists should be convinced from the data that most patients [who convert to node-negative disease] can avoid regional nodal radiation.

What should colleagues be aware of when considering the use of radiation therapy in these patients?

It is important to emphasize to patients who will do well [without regional nodal radiation]. The number of [recurrence] events was low, survival was good, and this is a great message for patients.

Even if [there are concerns] that lead to the decision to treat regional nodes [in a patient who converted to node negative], the key message is that the patient responded well to chemotherapy by converting from node positive to node negative. Patients need to hear that.

The majority of these patients likely do not need regional radiation, and those who had a mastectomy probably don’t need post-mastectomy radiation. However, not [all patients] are the same. Let’s look at subsets of patients and any other [disease characteristics] that you’re concerned about.

Reference

Mamounas E, Bandos H, White J, et al. Loco-regional irradiation in patients with biopsy-proven axillary node involvement at presentation who become pathologically node-negative after neoadjuvant chemotherapy: primary outcomes of NRG Oncology/NSABP B-51/RTOG 1304. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, Texas. GS02-07