No Survival Dip After Skipping Axillary Surgery for Locally Advanced Breast Cancer

CHICAGO — Skipping axillary lymph node dissection (ALND) for selected patients with locally advanced breast cancer did not adversely affect survival, findings from a randomized trial showed.

Patients who omitted ALND after a positive sentinel lymph node biopsy (SLNB) had a 5-year overall survival (OS) rate of 94.4% as compared with 93.4% for those who underwent completion ALND. Arm symptoms occurred less frequently with omission of ALND, and severe problems with arm function occurred more than three times as often in patients who had completion ALND.

Almost all patients had radiation therapy, and completion ALND detected additional cancer in a third of cases, reported Jana de Boniface, MD, PhD, of the Karolinska Institute in Stockholm, at the American Society of Clinical Oncology (ASCO) annual meeting.

“Survival after omission of completion ALND is noninferior to completion ALND,” de Boniface said during a press briefing prior to the meeting. “Omission of completion ALND results in significantly less arm-related complications, better quality of life, and better arm physical function.”

Therefore, “omission of completion ALND should be standard of care in breast cancer that has spread to one or two sentinel lymph nodes,” she added. “This recommendation needs to be viewed in the context, of course, that adjuvant local-regional radiotherapy was received by most patients in the SENOMAC trial. At the moment, we have another ongoing randomized trial, the T-REX trial, which looks at the omission of local-regional radiotherapy in the same patient group.”

The results build on an earlier report from the trial showing no significant difference in recurrence-free survival between the two treatment groups. Additionally, a post hoc analysis of the trial showed that completion ALND did not help identify patients who would benefit from adjuvant treatment with a CDK4/6 inhibitor.

SENOMAC added more evidence to inform discussions about treatment de-escalation in breast cancer, said invited discussant Jane Meisel, MD, of Emory University and Winship Cancer Institute in Atlanta.

“It’s so important to be looking at these questions and asking how can we possibly do less with potentially the same or better outcomes because there are so many survivorship issues, such as lymphedema and arm function, that we don’t think about as often as we should in the context of thinking about curing breast cancer,” she said. “These are things that continue to plague patients over the years as they survive and beat the disease.”

“What this study shows is that for these patients with cancer that spread to one or two sentinel lymph nodes, we really can safely omit axillary lymph node dissection, especially if they are able to receive adjuvant local-regional radiation,” she noted. “As you said, the omission of radiation is something that will also be studied.”

The randomized trial design and inclusion of patients with tumors larger than 5 cm make the results widely applicable to a large population of women with breast cancer, Meisel continued. Primarily enrolling patients in Sweden and Denmark, the trial lacked the ethnic diversity of patients in other parts of the world.

“Overall, though, this adds a lot of strength to the idea that we probably could be doing less surgery and should be doing less surgery for patients with a lower burden of lymph node involvement,” she said. “Putting some of this into clinical practice may allow us to improve arm physical function, appearance, body image — so many things for our breast cancer survivors around the world.”

Historically, a positive SLNB necessitated completion ALND to ensure removal of additional cancer that lymph nodes might harbor, said de Boniface. Axillary surgery may lead to multiple arm-related complications, such as pain, swelling, loss of sensation, and functional limitations.

Previous studies suggested that completion ALND might not be necessary, but the studies lacked statistical power and excluded key patient groups, such as those needing mastectomy and those with larger tumors, de Boniface noted. SENOMAC addressed the question of whether ALND can be omitted without adversely affecting survival in breast cancer that has spread to one or two lymph nodes.

The trial had no limitation on the size of the primary breast tumor, enrolled men and women, and either breast conservation or mastectomy could be performed. Eligible patients had involvement of one or two sentinel lymph nodes with macrometastases, defined as >2 mm. Patients with abnormal lymph nodes on palpation were excluded.

All patients had SLNB after surgery, and those with involvement of no more than two nodes were randomized to completion ALND or no ALND. Patients received additional postoperative treatment in accordance with standards of care. The primary endpoint was OS, and the trial had statistical power to show noninferiority of no ALND to completion ALND.

Investigators in five countries enrolled 2,766 patients, 2,540 of whom were included in the per-protocol data analysis. The study population included 919 patients who underwent mastectomy — the largest number ever in a trial of this type, said de Boniface — and 147 who had primary tumors >5 cm.

After a median follow-up of 60 months, the primary analysis showed that omission of ALND demonstrated noninferiority, as the hazard ratio actually showed a slight trend favoring omission (HR 0.89, 95% CI 0.67-1.17, P<0.001 for noninferiority).

Patients allocated to completion ALND had substantially more arm symptoms and adverse effects on arm function at every assessment during the trial, said de Boniface. Severe/very severe problems with arm function occurred in 12.6% of patients who had completion ALND as compared with 3.6% of patients who omitted ALND. Global health-related quality of life favored ALND omission throughout the study and achieved statistical significance after 3 years.