Nodal Involvement Impacts Surgical Management of Axilla in Breast Cancer

In Clinical Studies News by Barbara Jacoby

By: Caroline Seymour


A sentinel node biopsy is a less-intensive alternative to a complete axillary lymph node dissection in breast cancer, but it is not appropriate for every patient with lymph node involvement, according to Hernan Vargas, MD, FACS, and the decision between the 2 approaches is grounded in the patient’s initial treatment intervention.

“Axillary dissection has been around for 100 years; that’s the traditional approach; however, it’s fraught with [the risk of] lymphedema, range of motion difficulties, and chronic pain,” said Vargas. “Therefore, strategies have been developed in the past 20 years or so that have allowed for less-extensive surgery.”

Among patients who undergo surgery first, those with limited lymph node involvement may not need a complete axillary lymph node dissection, according to data from the phase III ACOSOG Z0011 trial. At a median follow-up of 9.3 years, the 10-year overall survival (OS) rate was 86.3% among patients who underwent a sentinel node biopsy alone versus 83.6% among those who underwent a complete axillary lymph node dissection (HR, 0.85; 1-sided 95% CI, 0-1.16; noninferiority P = .02).

Data are not as robust among node-positive patients who receive neoadjuvant chemotherapy, said Vargas. However, a lack of response may indicate the need for more intensive therapy with a complete axillary lymph node dissection.

In an interview during the 2020 OncLive® State of the Science Summit on Breast Cancer, Vargas, a breast surgeon at Virginia Cancer Specialists, discussed the criteria that are used to determine the appropriate surgical intervention for patients with node-positive breast cancer and shared questions that still need to be addressed in the space.

OncLive: Could you discuss the current management of the axilla in breast cancer?

Vargas: The management of the axilla in patients who present with operable breast cancer and limited nodal disease [is] an evolving area. It is perhaps a bit more controversial [as opposed to what is being done in] patients with negative nodes who are managed with sentinel node biopsy, and those with extensive disease or more nodal involvement who are managed with axillary dissection.

The evolution of the management of the axilla parallels the management of patients with cancer; with the increasing success of therapy, we are able to focus a lot more on the patient’s quality of life. We’re able to de-escalate surgery and de-escalate different treatments. We’re moving away from extensive axillary dissection to more limited evaluation of the axilla and sentinel node biopsy across all areas of oncology. Targeted sentinel node biopsy [has become a preeminent approach in that regard].

How do you determine whether a patient needs a complete axillary lymph node dissection?

In patients with locoregional disease who require therapy, surgery has to play a role in their management. When patients undergo surgery first, the key is to have appropriate selection criteria to [determine whether to] de-escalate surgery and therapy. Patient selection also plays a critical role in patients who receive neoadjuvant chemotherapy or systemic therapy. However, in that context, we have a bit more information because we know how the patient responded to chemotherapy.

How are de-escalated approaches being implemented in practice?

[We can perform a] sentinel node biopsy, particularly in patients who have node-positive disease. De-escalation criteria are based on initial therapeutic approaches. If a patient is treated with surgery up front, de-escalated approaches might be based on [ASCOSOG] Z0011 criteria. This study [showed us that a patient should have] less than 3 positive nodes and no extranodal extension [to be eligible for a de-escalated approach]. The original trial only looked at breast conservation candidates and those who received breast conservation. However, I believe we have extended [those criteria] to patients who undergo mastectomy, as well.

For patients treated with neoadjuvant chemotherapy, the number 1 de-escalation factor is their response to therapy. Secondly, we have a strategy to identify those originally positive nodes—either by targeting them with a clip and ultrasound localization or by having a good number of sentinel nodes that allows us to have accurate representation of the axilla. Finally, it’s knowing that selecting patients who need axillary dissection is not a failure, but rather an appropriate targeted approach.

You mentioned the ACOSOG Z0011 criteria. Could you expand on that trial and other notable research efforts in this space? How have these studies impacted clinical practice?

The ACOSOG Z0011 and the European AMAROS trials [had the greatest impact on the way we treat] patients with node-positive disease who undergo surgery up front. Both trials enrolled patients with positive sentinel nodes and randomized them to axillary dissection. In the ACOSOG Z0011 trial, the experimental arm examined sentinel node biopsy alone; in the AMAROS trial, the experimental arm evaluated radiation alone. Both trials have shown comparable OS rates and statistically equivalent recurrence rates [with the experimental approaches compared with axillary dissection].

In terms of patients who receive neoadjuvant therapy, long-term data from [well-designed] prospective randomized trials [is lacking] in the node-positive population. Therefore, we infer from data yielded by other clinical trials conducted in the United States, Canada, and Europe. [These data show] that the successful identification of lymph nodes and a good false-negative rate meet the criteria and the right surgical technique [is employed].

What challenges remain in this space?

Currently, [the key challenge is figuring out how to] integrate these data into the multidisciplinary management of our patients. [We should work toward identifying] better ways to identify patients with estrogen receptor–positive, HER2-negative disease who may respond to some kind of neoadjuvant approach. The second challenge is how we view endocrine therapy [versus] neoadjuvant endocrine therapy. How do we manage those patients? We don’t have any data in that regard.

Two prospective randomized trials are examining the role of radiotherapy in node-positive patients with sentinel node biopsy alone. Additionally, how do we manage a patient who has achieved a complete response [to therapy]? How do we measure that, and how should we de-escalate surgery? How do we appropriately treat those patients? Even sentinel node biopsy has some toxicity. In an ideal world, we would have something [to offer our patients] that doesn’t have any toxicity.

Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318(10):918-926. doi: 10.1001/jama.2017.11470.