Evidence-Based Strategies Help Guide Need for ALND in Breast Cancer

Anees B. Chagpar, MD, MSc, MPH, MA, MBA

Axillary lymph node dissection (ALND) is the standard of care for patients with breast cancer who have positive sentinel lymph nodes after neoadjuvant chemotherapy, said Anees B. Chagpar, MD, MBA, MPH, FACS, FRCS(C). However, several evidence-based strategies may inform which patients can be spared the invasive procedure and of the toxicities associated with the approach.

"The consequences of ALND include lymphedema, decreased range of motion, and shoulder numbness,” said Chagpar. “It would be great if we could reduce our use of ALND without negatively impacting oncologic outcomes. In fact, there are a number of ways we can reduce ALND."

In an interview with OncLive, Chagpar, a professor of surgery in the Department of Surgery at Yale School of Medicine and assistant director of Global Oncology at Yale Cancer Center, outlined several strategies to minimize the use of ALND in patients with breast cancer.

OncLive: Are there some patients who can avoid ALND?

Chagpar: First, we have to think about when axillary evaluation is required at all. Several years ago, the Society of Surgical Oncology put out a guideline that said we need to try to avoid any kind of axillary staging in women >70 years old with estrogen receptor—positive breast cancer who have a relatively good prognosis and are clinically node-negative. In truth, those women have a low risk of having sentinel lymph node metastasis. Additionally, [ALND] would alter treatment from both a staging and local-control perspective. Finally, we know [ALND] does not impact survival. Perhaps we can avoid axillary staging [in this group of patients].

There are other strategies as well, some of which we already do in order to avoid ALND, such as sentinel lymph node biopsy. This is a minimally invasive technique that, if negative, informs us that we can avoid ALND completely. That is widely accepted.

Are patients with positive sentinel lymph nodes eligible for de-escalated approaches?

Another strategy is to think about invoking clinical trials that allow us to avoid ALND even in patients with positive sentinel lymph nodes.

Many of us are familiar with the ACOSOG Z0011 trial which showed that we can avoid ALND in patients who have tumors <5 cm, those who are undergoing a partial mastectomy followed by whole breast radiation, and those who have 1 or 2 positive sentinel lymph nodes. As such, many of us use those criteria [to determine which patients can benefit from a de-escalated approach].

However, what do you do if a patient is undergoing a [radical] mastectomy or not receiving full breast radiation? Those patients do not fit the ACOSOG Z0011 criteria. Do you have to complete the ALND? Not necessarily.

There are 2 other trials we should be familiar with. The IBCSG 23-01 trial looked at patients who had >1 positive sentinel node. A number of these patients underwent mastectomy, and a number of them did not have radiation. Patients had to have micrometastases less than 2 mm [to be eligible for enrollment]. Therefore, if a patient who has 4 positive micrometastatic nodes is having a mastectomy without full breast radiation, you can invoke the IBCSG 23-01 trial.

What if the patient had macrometastases? In that case, we think about the AMAROS trial, in which a number of patients had macrometastases. These patients also had a mastectomy, and a number of them did not have radiation therapy. When comparing ALND versus axillary radiation alone, the local recurrence rates were low with more than 6 years of follow-up. Additionally, lymphedema rates were lower in the axillary radiation group than in the ALND group.

There are a number of evidence-based trials we should be familiar with that can help [reduce the use of] ALND in patients who are undergoing upfront surgery.

Could the use of neoadjuvant chemotherapy reduce the need for ALND?

The rates of neoadjuvant chemotherapy are increasing. [Neoadjuvant chemotherapy] is increasingly effective, particularly in patients with HER2-positive and triple-negative breast cancer. The addition of neoadjuvant chemotherapy can transform a good proportion of patients who are clinically node-positive to pathologically node-negative.

In the ACOSOG Z1071 trial, 40% of patients who were clinically node-positive converted to pathologically node-negative after neoadjuvant chemotherapy. As such, we know we can avoid ALND in those patients.

The SENTINA trial showed the same concept, except the proportion of patients who transformed from clinically node-positive disease to pathologically node-negative disease in arm C of the trial was even higher.

Sentinel lymph node biopsy after neoadjuvant chemotherapy is feasible and accurate. There has been talk regarding the false-negative rate, but we have tools available to reduce that. A good proportion of patients [who undergo neoadjuvant chemotherapy] are going to become pathologically node-negative, and can then avoid ALND. That is the third technique.

Can patients who remain node-positive after neoadjuvant chemotherapy be spared ALND?

[In that case], I would think about enrolling patients on clinical trials, such as the Alliance A11202 trial. This trial randomizes patients who have a positive sentinel lymph node after neoadjuvant chemotherapy to ALND—the current standard of care—versus no ALND.

The trial provides a good way to spare half of patients ALND, as well as help us advance the science.

Are there any other strategies that are being used in practice that you would like to highlight?

The final strategy is what all of us do regularly in our tumor boards, and that is to “waffle” a bit. By that I mean personalize therapy and think about how a particular strategy is going to affect a particular patient.

Is [a particular treatment] going to change outcomes in terms of the management strategy of the medical or radiation oncologist? What is the probability that patients will have residual positive lymph nodes? There are a number of nomograms in online clinical prediction models that may be helpful [in determining that].

What about for an elderly patient who has a number of comorbidities? Is ALND worth it? Is it going to change what we do? Is it going to affect local recurrence? We have to have those tailored discussions to help us decide whether ALND is worthwhile or not.