Less Invasive Techniques Transform Surgical Management of Breast Cancer

Judy C. Boughey, MD

Concerns over false-negative rates with sentinel lymph node biopsies have prevented the widespread adoption of sentinel lymph node surgeries in women with node-positive breast cancer. However, improvements in surgical techniques and the development of neoadjuvant therapies have allowed wider eligibility for the procedure, explained Judy C. Boughey, MD.

“With these techniques, we can drive that false-negative rate lower, enable more of our patients to be candidates for a sentinel lymph node surgery, and potentially avoid the morbidities associated with a complete axillary lymph node dissection,” explained Boughey.

Patients who are eligible for sentinel lymph node surgery show node negativity following neoadjuvant chemotherapy, noted Boughey. Although it may not be the predominant surgical approach, it offers a less invasive treatment approach for select patient populations.

“The dissemination of this possibility for patients has been going relatively well,” added Boughey. “It is a change, and the community oncologists and surgeons need to be comfortable with the data. They need to be aware of all of the tools in the toolbox.”

OncLive: What are the new techniques in the surgical management of women with node-positive breast cancer?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Breast Cancer, Boughey, chair of the Division of Surgery Research, Mayo Clinic, discussed the surgical management of the axilla in patients with node-positive breast cancer and less invasive approaches for disease management.Boughey: Women who have node-positive breast cancer are often treated with neoadjuvant chemotherapy. When patients have involvement in the lymph nodes at their initial presentation, the standard, up until several years ago, was to resect all lymph nodes with an axillary lymph node dissection.

Several prospective trials conducted in America, Canada, and Europe have looked at whether we can avoid doing a full axillary dissection and identify the patients in which neoadjuvant chemotherapy has effectively transitioned the lymph nodes from being positive to negative. This allows those patients to have a few lymph nodes removed with what's called a sentinel lymph node surgery; that way, we can limit the use of axillary lymph node dissection to those women who still have disease in their lymph nodes after neoadjuvant chemotherapy.

All 3 of those prospective trials showed a false-negative rate. There was an error rate around about 10% to 14%, depending on the trial. Since those trials have been published, there have been several improvements in technique that are driving down the false-negative rate and making the procedure as safe as possible for patients.

Examples of those techniques include making sure the surgeon uses a dual tracer—which is usually a radioactive colloid—and a blue dye, as that increases the identification rate of the sentinel node and decreases the false-negative rate associated with sentinel lymph node surgery. Another technique is using a clip that can be placed by the surgeon. Prior to chemotherapy, at the time of the needle biopsy, [the clip is placed] in the positive lymph node. Then, when the sentinel lymph node surgery is performed, [surgeons will] remove the clip node.

What are the recommended neoadjuvant therapies for women with node-positive breast cancer?

What is the benefit of surgical management of the axilla for patients?

A third technique that is being widely adopted is the use of immunohistochemistry. We’re encouraging our pathologists to look a little bit closer at the sentinel lymph node to identify what might be just small volumes of disease, isolated tumor cells, or foci of disease that are less than 1 mm or even less than 0.2 mm in size. Then, [pathologists should] consider those patients as node-positive and proceed with an axillary lymph node dissection.The neoadjuvant therapies for patients with node-positive breast cancer are continually evolving. In the past, the conversion rate in women who [went from] node-positive to node-negative when treated with neoadjuvant chemotherapy was 20% or 30%. Now, we're seeing conversion rates ranging from 50% to 60%, or even higher. Specifically, patients with HER2-positive breast cancer who receive chemotherapy with dual HER2-targeted therapy are showing conversion rates as high as 65% to 70%.If a patient had gone to the operating room when they were first diagnosed, the standard recommendation would have been an axillary lymph node dissection. Delivering the chemotherapy in the neoadjuvant setting gives that patient the benefit of seeing [an antitumor response] and a chance to consider less invasive surgery after completing chemotherapy.

What challenges are surgeons still facing with these patients?

What advice would you give to a team that wishes to adopt this practice?

These patients who may have required a mastectomy upfront may now be candidates for breast conservation, particularly if it's a unifocal tumor that has shrunk really well in the breast. Similarly, in terms of the axilla, the patient may have required an axillary lymph node dissection upfront but after achieving a good response to neoadjuvant chemotherapy, may be a candidate for sentinel lymph node surgery.Sentinel lymph node surgery is not for every patient; this is a technique for patients who have had an excellent response to neoadjuvant chemotherapy—–those who likely have no disease in the breast by imaging, those whose lymph nodes are likely negative. Those are the ideal patients who can benefit from this procedure. The rate of [successful sentinel lymph node surgery] is highest in patients with triple-negative breast cancer and HER2-positive breast cancer.If you're looking at utilizing sentinel lymph node surgery after neoadjuvant chemotherapy, sit down with a multidisciplinary team, as the procedure impacts all members of the team. If you’re a medical oncologist, you have to select the ideal patient for neoadjuvant chemotherapy and the regimens that should be utilized.

If you’re a radiologist, you have to image the axilla at the time of diagnosis. In these patients, I recommend a routine axillary ultrasound to evaluate the lymph nodes before chemotherapy. If a lymph node looks abnormal, proceed with a percutaneous biopsy, specifically a fine needle aspiration or a core needle biopsy. If it's positive, drop a clip in the lymph node and mark that lymph node the way we mark the breast lesion.

What’s coming down the pike for surgery?

Then, work with the radiation oncologist to determine how this impacts their thoughts on regional nodal irradiation after neoadjuvant chemotherapy. Additionally, you need to work with the pathologist on immunohistochemistry staining of the sentinel nodes [to determine whether the treatment was effective, whether it was node-negative and now node-positive, and how to report that]. It requires bringing the team together to adopt this new practice.We're seeing many patients who are having excellent responses to neoadjuvant chemotherapy. Surgeons are getting to the operating room at the time of the lumpectomy, mastectomy, and nodal surgery and finding that there's no residual disease in the breast or in the lymph nodes. This pathological complete response (pCR) is really what we want for our patients. We want to drive that pCR rate up.

Are there any existing data on women who may be eligible to forego surgery?

As we continue to be successful in individualizing medicine and advancing the systemic therapy that we're using, the pCR rate goes up. Surgeons have to keep asking what their role is and whether they have to be as aggressive as they have been in the past. There are some emerging clinical trials looking at whether we can avoid surgery on the breast in patients who have had an excellent response to neoadjuvant chemotherapy.Some of the data have shown that patients who have no residual disease in the breast after neoadjuvant chemotherapy also have a very high likelihood of not having disease in the lymph nodes. Data on a particular subset looked at patients who are clinically node-negative before neoadjuvant chemotherapy and had either triple-negative or HER2-positive tumors. If they were treated with neoadjuvant chemotherapy, and then at surgery they had no evidence of disease in the breast, greater than 97% had negative lymph nodes. [These findings] raise the question of whether the surgeon can avoid surgery on the axilla, which we know is associated with certain comorbidities. It would be an exciting advance to see less surgery in the breast and in the lymph nodes.