A European phase III clinical trial called AMAROS, found that axillary radiotherapy (ART) and lymph node surgery (axillary lymph node dissection, ALND) result in equivalent overall and disease-free survival at five years after treatment for women with sentinel lymph node positive early breast cancer.

However, a debilitating side effect known as lymphoedema was twice as common among women who underwent surgery.

Breast cancer cells can spread within the breast and throughout the body by different systems.

One of these is the lymphatic system.

When breast cancer cells travel through the lymphatic system, they may end up in a lymph node.

The first draining lymph node of a breast tumour is called the sentinel node.

After the sentinel node, the breast cancer cells can spread to the lymph nodes in the armpit, called axillary lymph nodes.

When the sentinel node contains breast cancer cells (which is called a ‘positive sentinel node’) and axillary treatment is indicated, surgical removal of all axillary lymph nodes (ALND) is currently the standard treatment.

Thousands of women undergo ALND every year to prevent breast cancer recurrence.

However, treatment with an ALND has substantial side effects, the most significant being lymphedema (long-term, painful swelling of the arm).

This study suggests that, for patients who need axillary lymph node treatment, ART is a good alternative to ALND and can reduce the risk of lymphoedema, without diminishing patients’ survival. ART can be combined with radiotherapy to the breast or chest wall, which most women already receive as treatment for their primary tumour.

“I am sure these findings will lead to many doctors re-thinking their strategy for treating patients who have a positive sentinel lymph node biopsy,” said lead study author Emiel J. Rutgers, MD, a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, Netherlands. “Lymphoedema is a serious concern for patients and a side effect that can affect their quality of life indefinitely.”

Four thousand eight hundred-six patients with early stage, invasive breast tumours up to five centimeters and clinically node negative (no signs of breast cancer spread to the lymph nodes before surgery based on tests, such as physical exam and imaging of the axilla), were enrolled in the study. Of those patients who had a positive sentinel lymph node biopsy, 744 were randomly assigned to ALND and 681 to ART. The median follow-up period was 6.1 years.

The five-year breast cancer recurrence rates in the axillary nodes were very low overall – 0.54 percent and 1.03 percent in the ALND and ART groups, respectively. There were no significant differences between the two treatment groups regarding the estimated five-year overall survival (92.5-93.3 percent) and disease-free survival rates (82.6-86.9 percent).

In contrast, there were striking differences in the numbers of patients who experienced lymphoedema. In the first year, 40 percent of patients in the ALND arm had lymphedema compared to 22 percent in the ART arm. In subsequent years, the number of patients with lymphoedema decreased, but the trend persisted: at five years the rates were 28 percent and 14 percent.

“While some controversy continues regarding the role of complete axillary lymph node surgery, this trial presents an important non-surgical option for selected patients to reduce breast cancer recurrence under the arm and substantially reduce the risk of arm swelling, which is too common and often debilitating for our patients,” said Andrew D. Seidman, MD, ASCO spokesperson and breast cancer expert.

Lymphoedema of the arm on the treated side of the patient is the most common side effect of both ART and ALND. The swelling of the arm is caused by a blockage in the lymphatic system in the axilla, an important part of the immune and circulatory systems. The blockage is due to the axillary treatment (ALND and/or ART) preventing lymph fluid from draining well. And as the fluid builds up, the swelling continues.

The arm feels heavier and its function is impaired. Frequently, patients have to wear firm sleeves around the whole arm to control the increase of swelling and many patients need specialised lymphoedema therapy. Other common side effects of both treatments are pain in the armpit area and shoulder function disturbances.

Researchers are working on ways to adjust radiotherapy with modern techniques to further diminish side effects of ART. In the future, complete surgical removal of lymph nodes in the armpit may no longer be necessary for most patients. Based on these findings, Dr. Rutgers said that this invasive procedure should be reserved for patients with extensive metastases in axillary lymph nodes who do not respond to adjuvant therapy and as a salvage therapy for patients who relapse.

This research was supported in part by the European Organisation for Research and Treatment of Cancer Charitable Trust.

Source: ASCO