Potential for Deintensification of Surgical Interventions in Low-Risk Breast Cancer

Studies have indicated that less-invasive approaches are possible for many patients with low-risk breast cancer, according to a recent review published in JCO Oncology Practice. Notably, many patients can opt for sentinel lymph node biopsies over axillary lymph mode dissection. In addition, the oncology community has been re-examining the level of margins needed in lumpectomies.

Background

Wider margins mean more surgeries, and greater physical and psychological impacts. Removing more tissue affects the ability to preserve the size and shape of the breast. Additionally, each excision brings anxiety as well as higher costs for patients.

Thanks to a better understanding of tumor biology, clinicians can make more informed decisions about the role that surgery plays in treating low-risk breast cancer. The JCO Oncology Practice article authors noted that "surgical approaches have continued to advance, with two major areas of deintensification being surgical margins and management of the axilla." For example, the 21-gene assay OnctotypeDx is often used for determination of adjuvant systemic therapy and may help de-escalate axillary surgical recommendations.

Considering surgical margins

“When it comes to surgical margin status, clinicians are moving beyond the belief that ’more is better’ for patients with early-stage invasive breast cancer,” says Cleveland Clinic Cancer Institute Breast Surgeon Vincent Wu, MD.

In a retrospective study of more than 50,000 patients with early-stage invasive breast cancer, the difference in local recurrence rates was negligible between those with "no tumor on ink" vs. those with wider margins. Data shows that there appears to be no statistical benefit for having margins in excess of 1 mm for patients with early invasive disease.

Since this study was reported out, the Society of Surgical Oncology, the American Society of Clinical Oncology and the American Society of Radiation Oncology now concur that margins should be 2 mm for patients with DCIS. This recommendation has a major impact on patients by reducing the need for re-incisions.

Reducing the need for axillary surgery

The other major advancement in surgical interventions involves axillary surgery. Previously, virtually all patients with breast cancer had to go through axillary lymph node dissection. This procedure comes with a 20-50% risk of lymphedema and up to a 75% risk of dysfunction of the arm or shoulder.

Performing sentinel lymph node biopsies make it possible for many patients who are node negative to avoid axillary lymph node dissection. Questions remain about whether all patients with positive sentinel nodes still require this procedure.

• The American College of Surgeons Oncology Group’s Z0011 trial studied 901 women with clinical T1 hormone-positive HER-2 negative breast cancer with involvement of one to two sentinel lymph nodes. Patients were randomly assigned to either receive axillary lymph node dissection or no additional surgery following lumpectomy and whole breast radiation.
  
  At a 10-year follow-up, there was no statistical difference in survival between those who underwent axillary lymph node dissection and those who did not. However, the study did not meet its accrual goals. Note: the types of radiation given post-surgery were not consistent among the study participants.
  
• The AMAROS trial studied a similar question, with 1,425 patients randomly assigned to receive axillary lymph node dissection or axillary radiation. At the 10-year follow-up, there was no difference in survival found between the two groups. Patients in the axillary radiation therapy cohort had lower rates of lymphedema (12% vs. 5% circumference at five years).
  
• A five-year follow-up in a similar trial (SENOMAC) of 2,766 patients with T1-2 breast cancer and one to two metastases found no difference in recurrence-free survival between those patients receiving axillary lymph mode dissection concurrently with lumpectomy and those receiving no dissection. The majority of patients in the trial did receive axillary radiation therapy.
  
• Studies found that sentinel lymph node biopsies and removal of previously involved lymph nodes were appropriate for patients with known axillary lymph node disease who had achieved a complete response in the lymph nodes to neoadjuvant systemic therapy. “There is an active clinical trial investigating whether omitting axillary lymph node dissection in favor of radiation therapy is appropriate in these patients,” says Dr. Wu.
  
• The Sentinel Node vs. Observation After Axillary Ultrasound (SOUND) study randomized 1,405 patients with T1 breast cancer and a negative axillary ultrasound to axillary surgery and sentinel lymph node or no axillary surgery. At a five-year follow-up, there was no statistical difference in disease-free survival between the two cohorts.
  
• In the INSEMA trial of 5,502 patients with clinically node-negative T1 or T2 invasive breast cancer, omitting surgical axillary staging was not inferior to sentinel-lymph-node biopsy. In the cohort of patients who did not have this procedure, there were fewer cases of lymphedema and greater arm mobility.

The current Society for Surgical Oncology guidelines support omitting sentinel lymph mode biopsies for patients 70 years or older who are clinically node-negative if they have early-stage hormone receptor-positive, HER2-negative breast cancer.

A multidisciplinary approach to treat deintensification

Since the standard of care for breast cancer involves a combination of radiation, surgery and systemic therapy, it only makes sense that deintensification decisions should involve specialists from all three disciplines. Deintensification in one realm will certainly impact the other treatment modalities. It's prudent to coordinate multiple disciplines in the early decision-making and to keep lines of communication open throughout treatment to make adjustments in concert with one another as needed.

Learn about deintensification of systemic therapy for low-risk breast cancer.