Retrospective Data Show Aggressive Axillary Surgery Is Not Associated With Improved Outcomes in Select Patients With Breast Cancer

More aggressive axillary surgery was not associated with improved outcomes in patients with cN1 breast cancer that became ycN0 but remained node positive following neoadjuvant chemotherapy, according to findings from a retrospective analysis of patients treated in the phase 3 NSABP B-40 (NCT00408408) and NSABP B-41 (NCT00486668) trials presented at the 2023 ASCO Annual Meeting.

During the 2 studies, regional nodal irradiation and axillary surgery were selected at physician discretion and not protocolled. Patients underwent sentinel lymph node biopsy with or without axillary lymph node dissection, or axillary lymph node dissection alone.

Findings from the retrospective study showed that the 5-year risk of locoregional recurrence was 9% for those who underwent axillary lymph node dissection (n = 31) compared with 12% for those who received sentinel lymph node biopsy (n = 599; P = .7911). The 5-year risk of metastases was 31% and 26%, respectively (P = .7520). The 5-year risk of any recurrence was 33% and 32%, respectively (P = .7909).

“Right now, we are waiting for the results to mature from the phase 3 Alliance A011202 trial [NCT01901094]. In that void of time, we determined with this analysis of NSABP B-40 and B-41 that more intense axillary surgery, such as axillary lymph node dissection, was not associated with better cancer outcomes when compared to sentinel lymph node biopsy,” Raymond Mailhot Vega, MD, MPH, said in an interview OncLive^®.

In the interview, Vega delved into the rationale for exploring the outcomes of patients who underwent axillary surgery or sentinel lymph node biopsy, explained the implications of these findings, and detailed what eventual data from A011202 could mean for the breast cancer treatment paradigm. Vega is a clinical associate professor in the Department of Radiation Oncology at the University of Florida College of Medicine, in Jacksonville.

OncLive: Could you expand on the rationale for investigating the efficacy of axillary surgery in patients with breast cancer who have received neoadjuvant chemotherapy?

Vega: It is important to recognize that, in general, for the last 40 years, there has been a stepwise approach into how clinicians have approached who benefits from both axillary surgery—meaning surgery to the armpit region where there are lymph nodes—and radiation. That helped oncologists and practitioners define which women benefit from having a full lymph node dissection, or if lymph nodes have been taken, who benefits from having comprehensive regional nodal radiation.

Those [past] clinical trials were done in a sequence of surgery first, followed by chemotherapy, and then ending with radiation. However, what's happened recently, is the beginning of neoadjuvant chemotherapy, where the first step, rather than being surgery, is chemotherapy. This has allowed for more women to proceed with a lumpectomy or preserving their breast if they want to. Consequently, [determining] who benefits from radiation and who benefits from a specific type of axillary surgery [remains an unmet need] as we await level 1 data from other randomized trials.

This specific [retrospective study] sought to answer that void while we're awaiting a larger, randomized control trial to answer that question.

What specific patient population was included in this study?

This focused on patients who were enrolled on NSABP B-40 and NSABP B-41. Those were 2 randomized clinical controlled trials which focused on different types of neoadjuvant chemotherapy. Patients from NSABP B-41 had HER2-positive disease, and patients from NSABP B-40 had HER2-negative [disease].

The real clinical questions being asked [in these prospective studies were surrounding] different types of systemic agents or chemotherapy. Both radiation and surgery were given a physician discretion. Therefore, we wanted to analyze, from that available data, if we could discern who possibly benefited from more intense axillary surgery.

What was the design of this study?

The actual data from NSABP B-40 and B-41 were from prospective, randomized, control trials. However, because we're trying to discern and tease out from those populations who benefited from a full axillary lymph node dissection or who benefited from a sentinel lymph node dissection, we conducted this by a retrospective analysis of these prospective trials.

What findings from this retrospective study were presented at the 2023 ASCO Annual Meeting?

I do want to give a caveat: the ultimate level of evidence will be the results from the phase 3 Alliance A011202 trial to help guide and understand [treatment decisions] for patients who still have positive lymph nodes after neoadjuvant chemotherapy. Can radiation to the axilla or those comprehensive lymph nodes replace a more intensive axillary lymph node dissection?

From the data we presented, when comparing those populations for who received sentinel lymph node [biopsy] and who received a full axillary lymph node dissection, we couldn't discern that the more intense axillary lymph node dissection was associated with better outcomes.

What are some of the next steps or future implications of this research?

This is the second work of our group, and the first study focused on trying to determine which patients benefit from having regional nodal radiation. However, those 2 ideas are somewhat linked. What our group is looking at for the subsequent work is this 2 x 2 categorization of what we're presenting at this conference, which is the difference between sentinel lymph node dissection and axillary lymph node dissection. It will be important to keep in context if patients are receiving regional nodal radiation. Can we see a difference between those two types of groups? For example, if a patient has an axillary lymph node dissection, do they benefit from regional nodal radiation? In patients who have a sentinel lymph node dissection, does regional nodal radiation improve their outcomes?

Could expand on the rationale and design for the A011202 study and how those findings may further define the role of axillary surgery?

That will ultimately answer the question that our abstract suggests because that's a true randomized, controlled trial. Patients entered with clinically node-positive disease, meaning that at the time that diagnosis happens, before receiving any type of treatment, there is involvement of lymph nodes in the axilla.

Those patients received chemotherapy before surgery, and specifically to enter, these patients still had lymph nodes that were positive at the time of completing their neoadjuvant chemotherapy. That [trial] asked if radiation is superior to or equivalent to axillary lymph node dissection. [This will help] better guide if patients need a full surgery that removes all of that fat tissue and the lymph nodes in that area. However, it's associated with a higher risk of lymphedema, which is an adverse effect where a patient has a painful arm that can limit their mobility.

[In the NSABP studies], both radiation and axillary surgery were given at physician discretion. What we had [examined in the] first analysis for regional nodal radiation was that when we accounted for tumor size, did patients have disease that responded to the neoadjuvant chemotherapy? Was it still present at the time of surgery? We determined that patients who are Hispanic received radiation significantly less often than their non-Hispanic counterparts.

Through that equity lens, it's important to remind practitioners, patients, and caregivers to advocate and evaluate what could be leading to that and to ensure that our treatments are appropriately being evaluated for these underrepresented or historically marginalized populations.

Reference

Vega RM, Deladisma AM, Mobley EM, et al. Axillary surgery efficacy for patients with breast cancer receiving neoadjuvant chemotherapy on NSABP B40 and B41. J Clin Oncol. 2023;41(suppl 16):534. doi:10.1200/JCO.2023.41.16_suppl.524