Accuracy of Sentinel Lymph Node Biopsies Are Vital to Inform Treatment Decisions in Breast Cancer

Anna Weiss, MD

The evolving treatment landscape across breast cancer has escalated the need for the accuracy of sentinel lymph node biopsies following treatment with neoadjuvant chemotherapy to correctly inform subsequent treatment decisions for patients, according to Anna Weiss, MD.

“Accuracy is important for our medical oncology colleagues because, more and more, treatment decisions are personalized to the patient and are dependent on the response that the patient has had. Therefore, if we as surgeons don't do an accurate procedure, and [for example,] we miss residual disease, that completely changes a patient’s adjuvant treatment regimen,” Weiss explained in an interview with OncLive^® following a State of the Science Summit™ on breast cancer, which she chaired.

In the interview, Weiss discussed the role of sentinel lymph node biopsies in breast cancer and the technical approaches needed to conduct them, key clinical trials that could affect the role of axillary surgery, the effect of fam-trastuzumab deruxtecan-nxki (Enhertu) on the HER2-positve treatment landscape, and the continued expansion of the multidisciplinary effort needed to treat breast cancer.

Weiss is the director of the Comprehensive Breast Cancer Program, the program leader of Breast Surgery, and the director of the Breast Cancer Service Line, at the University of Rochester Medical Center, Wilmot Cancer Institute, in Rochester, New York.

OncLive^®: What role do sentinel node biopsies currently play in breast cancer treatment?

Weiss: Sentinel lymph node biopsy is safe for most patients [with breast cancer] after neoadjuvant chemotherapy. However, you must consider the technical factors that you employ during sentinel lymph node biopsy to reduce the false negative rate and make it a more accurate procedure, especially in patients who presented with nodal disease.

What techniques are used for a sentinel lymph node biopsy, and which patients should be receiving them?

We should be doing a sentinel lymph node biopsy for most patients who present with clinical node-positive disease. However, we must be thoughtful about how we do this.

As surgeons, we use dual tracer. Some [surgeons] and institutions stain the lymph nodes for breast cancer cells using immunohistochemistry, and most people use a clip in the biopsied lymph node that we then try to retrieve. We make sure that we’re testing the biopsy-proven node before surgery and before treatment, then making sure we’re retesting the same one by retrieving that clipped node afterward.

There are a lot of different maneuvers that [a surgeon] can do. However, you must employ some combination of those to make it a more accurate procedure.

How have the addition of new treatment options in breast cancer affected surgical strategies for these patients?

The strategy for us as a community has changed in a few ways. Firstly, as surgeons involved in this multidisciplinary care plan, minimizing axillary surgery and minimizing the resultant morbidity of lymphedema is a top priority for all clinicians, regardless of whether they’re surgeons or medical oncologists. Everyone supports removing less lymph nodes. Our role in this as surgeons is to design the appropriate trials to show that it’s safe to remove less lymph nodes.

Our relationship with radiation oncology has also changed in a couple of ways. There are trials in radiation oncology looking at de-escalating or omitting radiation if a patient has had a complete response to their neoadjuvant chemotherapy. Again, if we aren’t doing an accurate sentinel lymph node biopsy, and we aren’t detecting residual disease, there is a future possibility that those patients would then also not get radiation. So, we must be careful to detect residual disease so that patients get the appropriate local regional therapy, including radiation.

Regarding medical oncology, we must be careful to detect any residual disease because more and more in the past decade, [treatment decisions such as] capecitabine [Xeloda] for [patients with] triple-negative breast cancer and ado-trastuzumab emtansine [T-DM1; Kadcyla] for [patients with] HER2-positive breast cancer depends on the presence of residual disease. If we, the surgeons, miss that, it will have survival implications for the patient.

Regarding the surgical space in breast cancer, how are unmet needs currently being addressed in clinical trials?

[Questions around the role of] axillary surgery after neoadjuvant chemotherapy will be mostly answered by the phase 3 ALLIANCE A011202 trial [NCT01901094] and the TAXIS trial [NCT03513614]. These trials that are randomizing patients with residual nodal disease to either axillary lymph node dissection or axillary radiation therapy.

In these patients, we find the residual nodal disease, which is important for radiation, medical oncology, and systemic therapy decisions. These trials [will answer the question] of what to do after detection [of residual nodal disease]; do we conduct the axillary lymph node dissection or radiate? These trials are going to be practice changing, because if they are positive, we’ll be able to stop doing axillary lymph node dissections for those patients.

The problem is, [the trial] results are expected several years from now. In the meantime, some of the work that’s being done by more multi-institution collaborations is looking at retrospective data. We can strengthen [our practice patterns] by looking [at these data] together. This provides the opportunity to look at the follow-up of patients who may not have had an axillary lymph node dissection in this setting. There are not a lot of robust data to support [axillary lymph node dissection vs radiation] one way or another.

Patients are being managed differently in the community. If we can study these real-world experiences and see [what the outcomes were for] patients that went from sentinel node biopsy straight to radiation we might be able to answer this question for clinically node-negative patients before the results of [the ALLIANCE A011202 and TAXIS] trials come out. That, to me, is where we need to focus.

Ajay Dhakal, MBBS, of the Wilmot Cancer Institute, discussed managing HER2-positive breast cancer with antibody-drug conjugates (ADCs) and monoclonal antibodies. How could the emergence of trastuzumab deruxtecan potentially affect the surgical space?

The development of ADCs is phenomenal and moving at such a rapid pace. The use of trastuzumab deruxtecan for our patients has changed the way that [patients with] HER2-positive metastatic disease are treated. I suspect that we’re going to see the DESTINY-Breast trials continue to show that trastuzumab deruxtecan is superior to current treatments and will further improve survival in patients with HER2-positive disease.

As a surgeon, I don’t see a lot of change in my practice right now because trastuzumab deruxtecan is [currently] used in the metastatic setting. However, I suspect we will see this change very quickly and use it more in the neoadjuvant setting, as well.

Dhakal and Carla Falkson, MD, MBChB, MMed, of the Wilmot Cancer Institute, discussed the HER2-low landscape. What improvements need to be made to better identify this subset of patients?

The existence of this entity of HER2 low is dependent on being able to accurately detect HER2 receptors. What we need to see is more sensitive assays for HER2 receptors, and once we have that, we can better consider [patients with HER2-low disease] their own entity.

Right now, it’s a little bit challenging to do that because the assessment of [an immunohistochemistry of] 1+ or 2+ are subjective, which is how all of pathology has been. Even [in] estrogen receptor [ER] staining, we think of it as a gold standard. However, it’s still a pathologist looking at [the tissue] themselves, so even [ER] is subjective. We have just been doing it [this way] for a long time. However, with time and more sensitive assays, we can and will consider [HER2 low] its own entity. As of right now, I’m just a bit cautious, especially in the early breast cancer setting to change much based on [the emergence of HER2 low].

How can surgical and medical oncologists work together to continue to improve the multidisciplinary effort needed to treat patients with breast cancer?

My main takeaway for colleagues based on discussions of HER2 low, trastuzumab deruxtecan, other ADCs, and [how they relate to] the surgical world is that [treating patients with breast cancer] has been and will continue to be a strong multidisciplinary specialty.

The changes that are happening in increasing rates of pathologic complete response [pCR] and increasing rates of pathology can change what we do as surgeons, and vice versa. It is important to think about how our research affects our colleagues in these other specialties moving forward.

For example, using different chemotherapy regimens that lead to increased pCR rates, what does that do to surgery? Are we able to do more breast conservation? Are we able to omit more axillary dissections? On our side, what happens if we omit the axillary dissection? What happens if there are studies looking at omitting sentinel node [biopsies]? Is that the right thing to do for a patient treated with neoadjuvant chemotherapy, when I’ve been talking about how important the detection of residual disease is?

I want to impress upon people that we always have, and now more than ever, lived in a multidisciplinary world. We have to think about end points for our colleagues in all of our trials.