More Research is Required for Axillary Management in Patients with Breast Cancer

At the 21^st Annual Lynn Sage Breast Cancer Symposium, experts gathered to weigh in on data surrounding the latest methods of treatment for patients with breast cancer. One of these presentations was given by Andrea V. Barrio, MD, FACS, attending surgeon at Memorial Sloan Kettering Cancer Center in New York City, on the topic of axillary management after neoadjuvant chemotherapy. A topic that has many clinical questions that need more research to address them.

OncLive^®, a sister publication to Oncology Nursing News^®, had the chance to speak with Barrio about her presentation and where she sees axillary management methods heading.

Barrio: Can you provide some background for axillary lymph nodes in breast cancer?

OncLive^®: So today what I spoke about is the management of the axillary lymph node after neoadjuvant chemotherapy. We divided it into speaking about patients who were originally clinically node-negative prior to neoadjuvant chemotherapy and those that are clinically node-positive. We spoke initially talking about the use of central lymph node in clinically net negatives patients after neoadjuvant chemotherapy demonstrating sentinel lymph node biopsy is safe with a high identification rate, a low false-negative rate, and low rates of normal recurrence after neoadjuvant chemotherapy. And then we spent the rest of the time discussing unresolved clinical questions in clinically node-positive patients after neoadjuvant chemotherapy.

These trials primarily enrolled patients with what we call CN1 disease or limited disease and the lymph nodes. All of these patients had neoadjuvant chemotherapy followed by a sentinel node and an axillary lymph node dissection. In these trials, the identification rate of sentinel lymph node biopsy was a little bit lower than what we see in the outside surgery setting and the false-negative rate exceeded the 10% rate that we consider to be clinically acceptable. But with modification of the sentinel node biopsy technique, with the use of dual tracer mapping and retrieval of three or more sentinel nodes, the false-negative rate uniformly fell to below 10%, which is clinically acceptable.

Are there any challenges in treating this patient group?

What we lack in these patients is nodal recurrence data. So, we know that although these patients achieve nodal PCR and the false negative rates are low, we are still awaiting results from larger data sets looking at rates of nodal recurrence in patients and clinically node-positive patients who are treated without XR dissection. I think, unfortunately, what we're seeing is that there is a lot of extrapolation of other data in the upfront surgery setting and many surgeons and institutions are avoiding X-ray dissection in patients who still have disease in the sentinel node after neoadjuvant chemotherapy.

And I showed data demonstrating high rates of residual non-sentinel node disease, over 60% of patients who have a positive sentinel node after chemotherapy will have additional lymph nodes that also have cancer, and by leaving those behind, we don't really know the implications of long-term outcomes. I really stress the importance if you have any positive sentinel nodes, after neoadjuvant chemotherapy, it's very important to do the completion axillary lymph node dissection, because of a high likelihood of finding residual disease and a lack of data demonstrating safety of omission of axillary lymph node dissection in these patients.

What are some other unresolved clinical questions that still need to be addressed?

I think when we think about doing sentinel lymph node biopsy our primary groups that we target are patients that have what we call CN1 disease or limited disease in the lymph nodes. Patients that have locally advanced breast cancer or a group of patients that we still don't know if those patients are appropriate candidates for sentinel node biopsy, regardless of their response to neoadjuvant chemotherapy.

There have been very few studies that have looked at the feasibility of sentinel lymph node biopsy in locally advanced breast cancer patients and all have really demonstrated an unacceptable false-negative rate. But with modern systemic therapy, we're seeing that rates of nodal pathologic complete response, even among locally advanced cancer patients, are high and in our institution, we looked at locally advanced cancer patients' rates of normal PCR and saw that the rates were nearly 40%, and were not different between patients that had limited disease in the nodes, or more advanced disease in the nodes.

And so, based on this, we have developed a prospect of study, that I’m the principal investigator of, looking at sentinel lymph node biopsy after neoadjuvant chemotherapy in locally advanced breast cancer patients. And in this study, we are giving these patients chemotherapy, those who become node-negative, meaning I can't feel their lymph nodes after chemotherapy, we're doing a sentinel lymph node biopsy and then following that with a completion dissection to see how accurate the sentinel lymph node biopsy is in predicting residual disease. Our targeted accrual is 100 patients in the past two years, we've accrued 50, and so we hope that with the results of this trial, we might be able to change the way locally advanced breast cancer patients are treated in the future.

What do you hope oncologists take away from this data and presentation?

I think that with the use of neoadjuvant chemotherapy in node-positive patients, we're really trying to look to deescalate surgical care. Axillary lymph node dissection is a very morbid procedure, which results in long term risks of lymphedema, which I think is a huge quality of life issue for many patients. In clinically node-positive patients, we can use neoadjuvant chemotherapy to deescalate that surgical care, but we also have to recognize that by doing that we need to do it safely. So, we pick patients who have excellent responses to chemotherapy, the HER2 positive and the triple-negative breast cancer patients seem to have the best response and it's in those patients that we really see reductions in the likelihood of axillary dissection.

The hormone receptor-positive HER2 negative patients have a little bit of a less brisk response to neoadjuvant chemotherapy, but we can still downstage a substantial number of those patients. And I think by using neoadjuvant chemotherapy to deescalate surgery we're going to improve the quality of life for many breast cancer survivors. But as I said, it's really important to do this safely and to not omit axillary lymph node dissection after chemotherapy in patients who have residual disease in the nodes. Those patients still require axillary dissection until we have data demonstrating otherwise.