Omitting ALND Does Not Alter Systemic Therapy Decisions in Breast Cancer

Omission of axillary lymph node dissection (ALND) resulted in understaging of breast cancer patients with clinically node-positive disease, but was not associated with systemic treatment decisions in the upfront surgery and post-neoadjuvant setting, observational data suggested.

The findings came from a substudy of TAXIS, an international randomized trial testing either ALND or axillary radiotherapy (ART) following tailored axillary surgery in 500 patients, with two-thirds undergoing surgery upfront.

In patients with hormone receptor (HR)-positive/HER2-negative disease treated with upfront surgery, a similar proportion in the ART or ALND groups went on to receive adjuvant chemotherapy (55.9% vs 60.3%, respectively; adjusted odds ratio [aOR] 0.72, 95% CI 0.19-2.67), reported Walter Weber, MD, of University Hospital Basel in Switzerland, and colleagues.

And of those who underwent neoadjuvant chemotherapy, researchers observed no association with ALND and the proportion of patients who received subsequent systemic therapy, at 77.0% in the ART group and 71.4% in the ALND group (aOR 0.86, 95% CI 0.43-1.70). Moreover, no differences in the type of post-neoadjuvant chemotherapy or endocrine therapy used were observed between arms.

Overall, more positive nodes were retrieved in the ALND arm, the group detailed in JAMA Surgery.

“[T]he present results suggest that even in a patient population with high nodal burden that is likely to be heavily understaged when ALND is omitted, the use of ALND to determine the exact number of positive nodes does not change systemic therapy,” Weber and colleagues wrote.

“Therefore, although ALND may be considered in individual patients being treated by a multidisciplinary team, results of the present study suggest that nodal burden as determined by TAS [tailored axillary surgery] without ALND does not generally result in underuse of systemic therapy,” they added.

In a commentary accompanying the study, Oluwadamilola Fayanju, MD, MPHS, of the University of Pennsylvania in Philadelphia, and colleagues noted various limitations to the study, but suggested it “does provide reassurance that ALND should not be performed solely for the purpose of facilitating adjuvant therapy decision-making.” They added that “additional prospective findings from TAXIS and other trials will be needed to elucidate optimal approaches to limited axillary surgery and what the long-term oncologic implications of surgical de-escalation in the axilla will be.”

According to Weber and colleagues, their study — a preplanned prospective, observational, cohort study within the phase III OPBC-03/TAXIS trial — was the first “to prospectively assess the role of ALND to determine nodal tumor burden to inform systemic therapy” for patients with clinically node-positive breast cancer.

The analysis included 500 patients with confirmed clinically node-positive breast cancer (median age 57 years, 97.4% women) from 44 breast centers in six European countries. All patients underwent tailored axillary surgery and were randomized 1:1 to ALND or ART.

HR-positive/HER2-negative disease was most common (79.4%), followed by HR-positive/HER2-positive disease in 10%, triple-negative breast cancer in 7%, and HR-negative/HER2-positive disease in just 1% of the study population.

Of the 335 patients treated in the upfront surgery setting, 88.4% had HR-positive/HER2-negative disease. In the ART arm, the median number of lymph nodes removed during tailored axillary surgery was five (median of three positive). In the ALND arm, a median 19 lymph nodes were retrieved overall (with four positive). Four or more positive nodes were found in 33.8% of patients in the ART arm and in 58.9% of the ALND arm.

Among the 151 patients who underwent neoadjuvant chemotherapy, a median of four lymph nodes were removed in the ART arm during the tailored surgery, while the median number of nodes removed in the ALND arm was 15 (a median of two were positive in either scenario).

No differences were seen in the type of post-neoadjuvant chemotherapy used in the ART and ALND arms (capecitabine [Xeloda]: 13.5% vs 13.0%, respectively); (trastuzumab emtansine [T-DM1, Kadcyla]: 12.2% vs 14.3%) or in the type of endocrine therapy (aromatase inhibitors: 55.4% vs 46.8%; tamoxifen: 10.8% vs 7.8%).

Limitations cited by Fayanju’s group included the study’s observational design, the absence of a prespecified power analysis to optimize sample size, and the fact that it included a low number of patients with HR-negative/HER2-positive disease.

The editorialists also pointed out that further study is needed to see whether limiting axillary surgery will affect systemic therapy decisions regarding CDK4/6 inhibitors in HR-positive breast cancer.