Should we continue to perform sentinel node biopsy in older-aged women?

Background

In the late 1800s, Rudolph Virchow and William Halsted proposed that lymph nodes in the axilla could behave as a nest of cancer cells that eventually spread systemically. Though both believed that patients with negative lymph nodes were cured, long-term follow-up showed that 20 to 30% of these patients developed distant metastases. Researchers tested the importance of lymph nodes in the systemic spread of breast cancer in the 1970s with a clinical trial. The National Surgical Adjuvant Breast and Bowel Project-04 was a randomized study of women placed into three strategies: axillary lymph node dissection (ALND), axillary radiation, or observation. Of the 365 node-negative patients who did not undergo ALND or radiation, 65 (17.8%) developed clinical lymph node metastases within ten years, requiring a delayed dissection. However, there was no difference in mortality among women in the three arms of the study. Despite these results, ALND continued to be performed as a method to determine who would benefit most from adjuvant chemotherapy. It wasn’t until the mid-1990s that the extent of axillary surgery began to wane with the advent of sentinel node biopsy. Multiple clinical trials, including those from Italy, the UK, and the USA, validated sentinel node biopsy, eliminating many ALNDs.

Studies omitting sentinel node biopsy in older patients

In a study from Milan in the journal Cancer (Agresti et al.;2014 120:885 – 893), 219 women aged 65-80 years with clinically negative nodes underwent breast-conserving surgery. Then they were randomized to undergo an ALND or no axillary surgery. All patients received tamoxifen for five years. At five years, there was no difference in breast cancer-specific mortality, overall mortality, or incidence of breast events between these two groups at five-year follow-ups. In a separate retrospective study from Milan (Madtrelli et al. Breast Cancer Res Treat 2021; 24:614-617), examiners evaluated a cohort of 661 clinically node-negative patients aged 70 years and older. One hundred seventy-two underwent ALND, while 499 received no axillary surgery. They found no difference in breast cancer mortality between the groups after 15 years of follow-up.

In the International Breast Cancer Study Group trial 10-93 (Rudenstarm et al. J Clin Oncol 2006 Jan 20;24(3):337-44), 473 women aged 60 years or older who underwent breast surgery were randomized to undergo either ALND or no axillary surgery. All women took tamoxifen for five years. The primary endpoint of this study was quality of life, and it was significantly improved in patients having no axillary surgery. Disease-free and overall survival were similar for the patients in these two arms.

Researchers at the Royal Marsden Hospital in London also published a study in which 194 low-risk patients with clinically negative nodes were randomized between ALND and no axillary intervention (O’Connell et al. Eur J Surg Oncol 2016; 42:942-48). The authors described low-risk patients as postmenopausal, with ER-positive tumors measuring from 1.5 to 2 cm, and with no lymphovascular invasion. The median follow-up was 10.4 years, and axillary recurrences were rare.

After examining the evidence, the American Board of Internal Medicine’s Choosing Wisely (CW) now recommends the omission of axillary surgery, including sentinel lymph node biopsy for all clinically node-negative patients aged 70 years or older with early-stage ER-positive, HER2-negative invasive breast cancer (Boughey et al. Ann Surg Oncol 2017:24,614-17). Furthermore, the Society of Surgical Oncology advises surgeons not to routinely use sentinel node surgery in women older than 70 who have hormone receptor-positive breast cancer (Welsh et al. Ann Surg Oncol 2017;24:2881-88).

With the great strides in tumor biology, we appear to be at a precipice where the requirement for any axillary surgery in specific subsets of women will be unnecessary. Currently, this is likely applicable to older women with hormone-positive, HER2-negative breast cancer. However, it should be noted that there are currently several ongoing studies where all age groups are included in the randomization of patients into axillary versus no axillary surgery.