A Trio of New Approaches for Breast Cancer Surgery

By Fred Hutch Staff · September 23, 2022

Future breast cancer treatment options may not only increase patients’ survival but also reduce or eliminate their need for surgery altogether, says breast cancer surgeon Sara Javid, MD, Fred Hutchinson Cancer Center’s Breast Health Clinic Director and University of Washington Professor.

Sara H. Javid, MD

New research is helping breast cancer specialists understand which patients may be able to avoid surgery and axillary lymph node dissections after neoadjuvant chemotherapy. Recent advances also include new surgical techniques to reduce the risk of lymphedema after axillary node dissections, Dr. Javid says. In particular, she noted studies on:

#1. Eliminating the need for breast cancer surgery after neoadjuvant chemotherapy

Early clinical trials of neoadjuvant therapy found that about 25% of patients downstaged from mastectomy to breast-conserving surgery without any increase in the risk of local recurrence, which remained about 10%.

Among patients receiving breast-conserving therapy, more recent studies have recognized the importance of pathologic clinic response (pathCR) vs. complete clinical response in predicting recurrence. For example, a 2016 study of 751 patients with triple negative or HER2+ breast cancer found the 5-year local recurrence rate was <3% in patients who had a pathCR. That compares with 10% to 13% for patients with no pathCR.

Other studies found that pathCR rates vary significantly based on histological subtype. Patients with HR+/HER2- breast cancer have much lower pathCR rates than triple negative and HER2+ patients.

“If we can identify select patients, called “exceptional responders” who will have a pathCR following neoadjuvant chemotherapy, in the future we may be able to consider forgoing surgery for these select patients,” says Dr. Javid.

Predicting pathologic complete response with image-guided biopsies

Past attempts to treat breast cancer without surgery after neoadjuvant chemotherapy resulted in high recurrence rates. This is mainly because physicians assessed clinical response based on physical exam and imaging results rather than pathCR.

A clinical trial published in 2018 looked at the feasibility of using image-guided biopsies to predict residual breast cancer after neoadjuvant therapy. The trial included 40 patients with triple negative and HER2+ breast cancer. The researchers concluded:

The overall pathCR rate was 48%.
Radiologic response was a poor predictor of pathCR.
Image-guided biopsy can accurately identify residual disease in most patients.
A minimum of 12 image-guided vacuum-assisted core biopsies is recommended.

“Tissue is the issue,” says Dr. Javid. “Image-guided tissue sampling, in combination with breast imaging and exam, is the most effective means to determine pathCR after neoadjuvant chemotherapy.”

A phase 2 trial is currently underway at four centers in the U.S. to study eliminating breast cancer surgery in triple negative and HER2+ exceptional responders to neoadjuvant therapy.

#2. Sentinel lymph node biopsy following neoadjuvant chemotherapy

Axillary lymph nodes also respond well to neoadjuvant therapy. Overall, about 40% of node positive patients are downstaged to pN0 after chemotherapy. The rate of downstaging varies by type, with higher rates in triple negative and HER2+ cancers. It does not vary by N stage.

“Based on this, we feel there is an opportunity to offer less aggressive axillary surgery, or sentinel lymph node biopsy, in place of axillary lymph node dissection,” says Dr. Javid.

A clinical trial published in 2013 looked at this approach in a series of 701 patients with T0 to T4, N1 to N2 disease following neoadjuvant chemotherapy. All patients received a sentinel lymph node biopsy and axillary lymph node dissection. The goal of the trial was to determine the false negative rate of pathCR with sentinel lymph node biopsy based on a pre-specified false negative rate threshold of 10%.

Initial results of the study showed overall false negative rates for N1 and N2 patients above the 10% threshold. However, further analyses revealed fewer false negatives with the removal of three or more sentinel nodes. Further improvements in the false negative rates were noted with the use of a dual tracer to map the sentinel nodes and removal of the clipped node that confirmed node-positive disease prior to chemotherapy.

This study and others have led to the development of the 2021 National Comprehensive Cancer Network guidelines for surgical axillary staging, which Fred Hutch follows.

The guidelines recommend placement of a clip into the node at the time of node positive diagnosis. Patients who respond to neoadjuvant therapy in the axilla based on clinical and imaging findings should be offered a sentinel lymph node biopsy that includes:

Removal of 3 or more sentinel nodes
Retrieval of the clipped node with localization via wire, radioactive seed, or radar reflector (targeted axillary dissection)
Use of a dual tracer (blue dye and radioactive dye)

#3. Surgical breakthroughs for reducing lymphedema after axillary node dissection

Lymphedema is a life-altering complication of axillary node surgery and can occur in 20-25% of women undergoing an axillary node dissection. “Some women decline axillary node dissection to avoid this dreaded condition,” says Dr. Javid. “Until now, treatments to reduce swelling, such as compression garments and physical therapy, have not been very effective.”

Emerging surgical approaches for reducing lymphedema include:

Axillary reverse mapping (ARM)

In this procedure, the surgeon injects blue dye into the arm to highlight the upper extremity-draining lymphatic channels. The theory is that the lymphatics that drain the arm are separate from those that drain the breast. During axillary dissection surgery, the surgeon can identify the arm's lymphatic channels and spare them.

A 2016 review of axillary reverse mapping noted several additional benefits. These include:
• No added morbidity or expense
• Reduced risk of lymphedema (from 33% to 6%)

The authors also identified several disadvantages. In 28% of cases, the sentinel lymph node is an arm node and must be removed. Patients with node-positive disease also have an as-yet undefined risk of cancer being harbored in remaining arm nodes, though this risk declines with neoadjuvant therapy.

Dr. Javid says that a randomized clinical trial will open soon at Fred Hutch to look more closely at cancer recurrence with axillary reverse mapping.

Lymphatic microsurgical healing approach (LYMPHA)

This approach also uses blue dye to highlight lymphatics in the arm. During axillary node dissection, the surgeon removes the arm nodes and attaches a clip to the lymphatic vessels. After the dissection, a plastic surgeon joins the lymph vessels to a collateral venous branch to allow for drainage.

In a small study of LYMPHA, the procedure was successful in 27 of 37 patients. Among those with a successful procedure, 12.5% developed lymphedema compared with 50% of unsuccessfully treated patients. These results and others suggest that LYMPHA may be feasible, safe and effective for the prevention of breast cancer-related lymphedema.

“We are currently offering this procedure to all women who undergo axillary dissection,” says Dr. Javid. “It adds about an hour to the operative time and the plastic surgeons are usually able to reconnect two to four channels. Our data show that the risk of lymphedema is 5% to 10% with LYMPHA, compared to over 20% without. The main concern is the cost of the procedure, which insurers currently do not cover.”

Breast cancer care at Fred Hutchinson Cancer Center and UW Medicine

Physicians at Fred Hutch and UW Medicine offer leading edge surgical therapies as well as the latest treatments in breast oncology.

For patient referrals contact:

Phone: (206) 606-1024
Fax: (206) 606-1025
Online referral form

Biopsy The removal of a sample of tissue or fluid that is examined to see whether cancer is present. This may be done with a large needle or through surgical removal of tissue or fluids. Biopsy The removal of a sample of tissue or fluid that is examined to see whether cancer is present. This may be done with a large needle or through surgical removal of tissue or fluids. Chemotherapy Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It may be given alone or with other treatments. Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, infusion or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy or biologic therapy. Clinical trial A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis or treatment of a disease. Imaging In medicine, a process that makes pictures of areas inside the body. Imaging uses methods such as X-rays (high-energy radiation), ultrasound (high-energy sound waves) and radio waves. Lymphedema A condition in which extra lymph fluid builds up in tissues and causes swelling. It may occur in an arm or leg if lymph vessels are blocked, damaged or removed by surgery. Recurrence Cancer that has come back, usually after a period during which it could not be detected. It may come back to the same place as the original (primary) tumor or someplace else. Also called recurrent cancer. Sentinel lymph node biopsy The removal and examination of the sentinel node(s), the first lymph nodes to which cancer cells are likely to spread from a primary tumor. The removal and examination of the sentinel node(s), the first lymph nodes to which cancer cells are likely to spread from a primary tumor. To identify the sentinel lymph nodes, the surgeon injects a radioactive substance, blue dye or both near the tumor. Next, the surgeon uses a probe to find the sentinel lymph nodes containing the radioactive substance or looks for the lymph nodes stained with dye. Then the sentinel nodes are removed to check for the presence of cancer cells. Stage The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer and whether the cancer has spread from the original site to other parts of the body. Staging Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from where it first formed to other parts of the body. Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from where it first formed to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment. LYMPHA Surgery to connect small lymph vessels to blood vessels so lymph has a path to drain into the bloodstream. LYMPHA stands for lymphatic microsurgical preventive healing approach.

Tags ·

lymphedema

breast cancer

breast cancer treatment

surgery

Back To: Provider Blog