Trial Explores Eliminating Breast Cancer Surgery in Exceptional Responders to Neoadjuvant Therapy

Henry Kuerer, MD, PhD

A prospective study is investigating whether breast cancer surgery can be eliminated in patients who respond well to neoadjuvant systemic therapy.

The phase II single-center trial, conducted out of The University of Texas MD Anderson Cancer Center (NCT02945579), aims to determine how often breast cancer recurs in patients who previously received chemotherapy and follow-up radiation therapy, but not surgery, and have no evidence of disease. Forty patients with early-stage, triple-negative or HER2-positive breast cancer care underwent image-guided biopsy after completing chemotherapy and before beginning radiation therapy to see if surgery is necessary.

With follow-up, explains lead author Henry M. Kuerer, MD, PhD, researchers will be able to determine whether surgery can, indeed, be avoided in these patients. A concern among many with breast cancer, he adds, is overtreatment.

OncLive: Could you give an overview of your discussion on surgical management in breast cancer?

Kuerer, a professor of Surgery at The University of Texas MD Anderson Cancer Center, lectured on surgical advancements in the field of breast cancer during the 2017 OncLive^® State of the Science Summit on Treatment of Metastatic Breast Cancer. In an interview, he discussed the goals of the prospective trial and how it could impact these exceptional responders.Kuerer: We are very excited about a new trial at The University of Texas MD Anderson Cancer Center that is just about to open. It is potentially groundbreaking for patients, in that we are going to try to eliminate breast cancer surgery for those who have an exceptional response to neoadjuvant therapy. We've known for quite some time that there are some patients with exceptional responses, even after a few cycles.

However, we particularly know for triple-negative breast cancer (TNBC) and HER2-neu—positive breast cancer that these patients overall, with standard therapies, have about a 50% chance of having no residual breast cancer at all. We have an obligation to test whether or not surgery is essential in those patients. The problem has been breast imaging; even the best and most advanced techniques cannot predict, with any accuracy acceptable to clinicians, who has no residual disease, and whether moving on to radiotherapy without surgery could be potentially dangerous.

The new trial is open to women with tumors that are less than 5 centimeters, are triple-negative, and HER2-neu. Patients who are responding and, in which we can sample with extensive vacuum-assisted biopsies at the end—just like we do at the beginning of therapy to make a diagnosis—and those patients without residual disease will go on to receive standard radiation without surgery.

We have moved to this point only with the completion of our feasibility clinical trial to assess whether or not we can accurately identify patients using biopsy with imaging to select patients without residual disease. Of course, safety is prime in our mind on testing this, so our completed clinical trial was for the same patient population of TNBC and HER2-neu. We had an endpoint of vacuum-assisted core biopsy along with fine-needle aspiration (FNA) to see the correlation of our ability to take that biopsy and to do our standard surgery and find out whether it is accurate.

Essentially, this trial met its endpoints with a very high accuracy that combines those techniques. Their accuracy was nearly 98% with a false-negative rate of 5% and a predictive value of about 95%.

With that data, we can be confident that when we sample extensively, it will likely be safe to just move on and have radiotherapy without the surgery. Of course, when you have 1 patient in whom you missed the residual disease, you focus on that particular patient. We learned a lot from the trial in that, on average, there were 12 vacuum-assisted core biopsies—which is very good sampling.

What does surgery look like to you in the next 5 to 10 years?

The 1 patient where the core biopsy and the FNA did not show any residual disease, but actually did have residual disease, was a limited sampling with only 4 core biopsies. We learned from that trial that we are going to need to do extensive vacuum-assisted biopsy for the clinical trial where we eliminate the surgery.What has changed so much over the years is the integration of neoadjuvant systemic therapy with surgery. Even for patients who present lymph node¬—positive disease, we now have a new technique called targeted axillary lymph node dissection. Here, we test the lymph node that had cancer prior to neoadjuvant therapy along with what we call the sentinel lymph nodes. We found that to be a very accurate method. We are eliminating more extensive surgery and lymph node surgery as well in probably 40% to 50% of cases.

With the emergence of liquid biopsies, do you foresee there not being a necessity for traditional biopsies?

What is the unmet need for a trial like this in breast cancer?

The key to the future of breast cancer, and all solid organs tumors, is more personalized with systemic therapies. Then, we only operate on patients who have residual disease that can't be eradicated with surgery.In our clinical trial, our hypothesis is going to be looking at circulating tumor DNA from the cancer cells and circulating tumor cells in correlation with the biopsies after neoadjuvant systemic therapy. Is it possible that, perhaps, the liquid biopsy or a blood test could tell us that there is no residual disease in the breast? These are some of the answers that we're looking forward to and excited about.Being in breast cancer research for such a long time, even at the beginning of my fellowship, I remember telling a patient after surgery that there was no residual cancer. At that time, we already knew that predicted for a very good prognosis with much higher survival rates for the individual patient.

Are there any challenges that you'd like to see overcome?

I always remember a patient who said to me, “Why did you remove my breast if there is nothing left?” This has been a passionate interest for us at The University of Texas MD Anderson Cancer Center—as well as on the patient side and nationally with other feasibility studies—which we hope will be replicated. There is a big interest in this—patients will tell me they don't want overtreatment.I have patients continuously ask if they really need surgery, and I used to say, “Yes, because we can't predict [recurrence],” but now we can. Part of the critical studies is not only financially looking at how this affects the healthcare industry with cost-savings but, on the patients’ emotional side, what will be her potential decisional regret?

We have several questionnaires administered throughout the trial looking at the quality of life of the patient who goes on to surgery versus those patients who don't have surgery—just radiotherapy—and some of those quality-of-life indicators, such as body image, depression, and how surgeries affect their quality of life, will be key questions that patients will want the answers to in the future.