Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: Final analysis of the EORTC AMAROS trial (10981/22023)
Reporter: Saumil Gandhi, MD PhD
The Abramson Cancer Center at the University of Pennsylvania
Last Modified: June 7, 2013
Presenter: Emiel J. Rutgers, MD PhD Presenter's Affiliation: Netherlands Cancer Institute
Axillary lymph node status is an important prognostic factor in women with early stage breast cancer and often guides adjuvant treatment decisions.
Sentinel node biopsy (SNB) is the standard of care in assessing axillary lymph node status of clinically node negative breast cancer patients and provides equal overall survival (OS) and disease free survival (DFS) compared to axillary lymph node dissection (AD) in patients with negative SNB.
In patients with positive SNB, if additional treatment is indicated, AD is the standard of care.
Benefits of AD include improved local control. In addition, AD provides information that guides prognosis as well as decisions regarding adjuvant treatment.
However, these benefits must be weighed against significant risks of lymphedema, nerve injury, and shoulder dysfunction associated with AD.
Axillary radiotherapy (ART) instead of AD was hypothesized to provide comparable regional control while minimizing the aforementioned toxicities.
An international, multi center, phase III study presented here compares AD with ART in patients with a positive SNB.
The main objective of the trial is to show that ART provides equivalent local/regional control compared to AD while reducing morbidity in patients with positive SNB.
From 2001 to 2010, patients with cT1-2N0 invasive breast cancer were enrolled in the EORTC phase III non-inferiority AMAROS trial.
Patients with multicentric disease, or those who received prior axillary treatment or neoadjuvant systemic treatment were excluded from the study.
Patients with positive SNB were randomized between AD and ART prior to breast conservation surgery or mastectomy.
ART included radiation to Level I, II, III and supraclavicular lymph nodes.
Primary endpoint was 5-year axillary recurrence rate.
Secondary endpoints were OS, DFS, quality of life (QOL), shoulder movement, and lymphedema at 1 and 5 years.
A total of 4,806 patients were accrued in the trial.
1425 (29.7%) of the patients were found to have a positive SNB. 744 were in the AD arm and 681 were in the ART arm.
The two treatment-arms were comparable regarding age, tumor size, grade, tumor type, and adjuvant systemic treatment.
146 patients in each arm were excluded due to ineligibility, incompliance, or presence of only isolated tumor cells in SNB (initially considered positive but later considered negative).
85% of patients completed the intended treatment in each arm.
With a median follow up of 6.1 years, the 5-year axillary recurrence rate after a positive SNB was 0.54% (4/744) with AD versus 1.03% (7/681) with ART.
The planned non-inferiority test was underpowered because of the unexpectedly low number of events.
The axillary recurrence rate after a negative SNB was 0.8% (25/3131).
There were no significant differences in 5 year OS between AD (93.27%) and ART (92.52%), p=0.3386.
There was also no significant differences in 5 year DFS between AD (86.90%) and ART (82.65%), p=0.1788.
AD was associated with significantly higher rates of lymphedema.
1 year: 40% AD versus 22% ART, p<0.0001
3 years: 30% AD versus 17% ART, p<0.0001
5 years: 28% AD versus 14% ART, p<0.0001
There was no significant difference in the risk of impaired shoulder function. However, there was a nonsignificant trend toward more early shoulder movement impairment after ART.
There were no significant differences in patient reported QOL outcomes in terms of arm symptoms, pain, and body image. There was a nonsignificant trend towards more difficulties with movement with ART and a trend towards more swelling with AD.
5 year axillary recurrence rates after AD or ART were far below hypothesized, thus the trial was underpowered to detect a difference.
Nevertheless, AD or ART in patients with a positive SNB provide excellent and comparable local/regional control.
ART reduces the risk of short-term and long-term lymphedema compared to AD.
ART should be considered the standard of care.
This is a well-designed phase III randomized study that shows that compares ART with AD for treatment of patients with positive SNB.
Within the AD group, 244 (32.8%) of patients had additional positive lymph nodes. However, the study showed that ART provides equivalent local/regional control as AD while reducing the risk of lymphedema by 50% in patients with positive SNB.
While ART is equivalent to AD in patients undergoing breast conservation surgery or mastectomy with lower rates of lymphedema, longer follow-up is needed to assess the late effects of ART on lymphedema, shoulder dysfunction, and QOL.
Finally, there is a large overlap between the characteristics of patients enrolled in this study and the ACOSOG Z0011 study where no axillary nodal treatment was given. Both studies included largely postmenopausal women with T1-2cN0 tumors with 1-3 positive nodes. By applying the Z0011 criteria to the patients on the AMAROS study, one might argue that a large percentage of women on this study did not need either ART or AD.
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