Six-month data from a large, prospective, randomized multicenter trial reported at the San Antonio Breast Cancer Symposium showed that sentinel node biopsy achieved improved quality of life compared with axillary node dissection in patients with invasive breast cancer.
Additionally, patients who had sentinel node biopsy exhibited significantly less arm dysfunction and were able to return to work earlier compared with those who underwent conventional axillary node dissection.
ALMANAC (Axillary Lymphatic Mapping Against Nodal Axillary Clearance) is the first large multicenter randomized controlled trial of sentinel node biopsy to utilize comprehensive quality-of-life assessment and objective assessment of shoulder function.
“At six months, quality of life is improved in these patients, with no increase in anxiety,” said Robert E. Mansel, MD, Professor of Surgery at the University of Wales, who reported the quality-of-life data. Mark Kissin, MD, a surgical oncologist at Royal Surrey County Hospital in Guildford, UK, reported ALMANAC data on lymphedema, shoulder function, and sensory loss.
ALMANAC is one of the largest multicenter trials comparing sentinel node biopsy with conventional axillary surgery. The study included 1,031 patients with invasive breast cancer who were randomized in a one-to-one ratio to both arms.
The patients' mean age was 57, and wide local excision was performed in 90% of patients prior to nodal procedures.
“This study represents one of the largest data sets on quality of life in breast cancer patients, with data on 829 cases,” Dr. Mansel said. Sentinel node biopsy was performed in 424 patients and standard dissection in 405 patients.
Only experienced, well-trained surgeons were included as investigators. The sentinel node was positive in 26% of patients and negative in 74%. Sentinel node-positive cases remained in the analysis and contributed the benefits favoring that arm.
The instruments used to measure quality of life were FACT B4 and STAI (Speilberger State-Trait Anxiety Inventory), a new anxiety scale. Domains assessed included breast cancer concerns and social, physical, and emotional well-being.
At baseline, quality of life was similar in the two groups. By the first month, however, there was a steep decline in quality of life in the axillary node dissection arm, and quality of life did not recover to baseline level during the following six months, nor did it recover to the level enjoyed by patients who underwent sentinel lymph node biopsy, Dr. Mansel said.
“At all time points, a significant difference favoring sentinel node biopsy was observed on FACT-6, STAI, and the arm morbidity subscale [reported separately at the meeting],” he said. Women in both groups showed the same anxiety levels.
In summary, Dr. Mansel said, the six-month data on sensory loss, arm swelling, and quality of life show a three- to four-fold difference favoring sentinel node biopsy.
Drain usage was 79% in the standard arm vs 17% in the sentinel node biopsy arm; this percentage included sentinel node patients who went on to more complete dissection due to positive nodes.
Hospital stay was about one day shorter in the sentinel node group; again, this included those with second surgeries.
Dr. Mansel, a member of the Editorial Board of OT's UK Edition, said that only properly trained surgeons should offer sentinel node biopsy. In the UK, all surgeons are being trained to perform this procedure, he noted. “This will be a unique program around the world.”
Lymphedema, Shoulder Function, Sensory Loss
“Sentinel node biopsy is a highly accurate method of assessing lymph node involvement, but prior to ALMANAC, we didn't have a lot of information about how the procedure affects patients' functioning,” Dr. Kissin explained.
Dr. Kissin, who presented six-month data on lymphedema, shoulder function, and sensory loss, said that ALMANAC patients would continue to be measured objectively for 18 months and then followed over the longer term. Eighteen-month data will be presented later this year.
“As a result of ALMANAC, we can tell our patients that there is objective evidence of benefit for sentinel node biopsy in terms of arm and shoulder function,” he said.
“Sentinel node biopsy should be the standard of care for patients with breast cancer. We should not be conducting a blind sample of all the lymph nodes, when in 75% of cases it isn't necessary. We should target the sentinel node instead.”
Lymphedema volume was measured by circumferential measurements of the upper arm and forearm. Shoulder function was assessed by gonio-tropic measurement of arm movement and patients' self-assessments.
Sensory deficits were assessed by self-reports and a pinprick method. The contralateral arm on the side of the body unaffected by breast cancer served as a control for objective measurements.
An intention-to-treat analysis showed a significant reduction in mild arm swelling at three and six months as reported by patients; moderate-severe swelling was observed in 1% of the sentinel node biopsy group vs 3% of the axillary node dissection group at three and six months.
Objective assessment also revealed a difference in swelling favoring sentinel node biopsy. Overall, at six months there was a significant reduction in lymphedema in the sentinel node biopsy group compared with conventional axillary node dissection.
An analysis at one of the institutions that participated in the study showed that at six months, lymphedema occurred in 3.4% of those who were sentinel node-negative and 11.3% who were axillary node clearance negative.
“Sentinel node-positive patients were no worse off than they would have been if they were axillary node-positive,” Dr. Kissin noted.
At six months, both groups had an equal degree of shoulder flexion. However, at one and three months, loss of shoulder flexion was greater in the group that had axillary node dissection. A similar pattern was observed for shoulder abduction. No differences were observed between the two arms for internal and external rotation.
“These data on shoulder function are married to the ability to resume normal activities at home and to return to work. Patients in the sentinel node biopsy group were able to do this more quickly than those in the axillary node dissection group,” Dr. Kissin said.
Study is Confirmatory
Commenting on the study, Monica Morrow, MD, noted that a single-institution study led by Umberto Veronesi, MD, published in 2003 in the New England Journal of Medicine showed that arm function and symptoms were improved in the sentinel node group compared with axillary dissection.
Dr. Morrow, Chairman of the Department of Surgical Oncology and the G. Willing Pepper Chair in Cancer Research at Fox Chase Cancer Center, added, “The ALMANAC study looks at quality of life, a slightly different way of looking at the same problem, because physical symptoms are related to quality of life, and confirms the findings of Veronesi et al in a larger population and a multi-institutional study.
“We would anticipate that with longer follow-up, the differences between groups would be more pronounced. Lymphedema is a lifelong problem, and the incidence increases with time.”