10-yr follow-up results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients
Reporter: Saumil Gandhi, MD PhD
The Abramson Cancer Center at the University of Pennsylvania
Last Modified: June 7, 2013
Presenter: Thomas B. Julian, MD
Presenter's Affiliation: University of Pittsburgh
- Axillary lymph node status is an important prognostic factor in women with early stage breast cancer.
- Axillary dissection (AD) and histologic examination of lymph nodes has traditionally been a routine component of surgery for patients with early stage breast cancer.
- 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.
- Tumor cells generally metastasize from the primary tumor to one or a few sentinel nodes (SN) before involving other lymph nodes.
- Sentinel node resection (SNR) is a less invasive method of staging the axilla with less morbidity compared to AD.
- In patients with clinically node negative breast cancer, negative SNR can identify patients without axillary nodal involvement, thus obviating the need for a more extensive AD.
- NSABP B-32 is a prospective randomized phase III trial designed to determine whether a less invasive SNR provides the same survival and regional control as a more aggressive AD in women with clinically node negative breast cancer.
- In this study, the authors present 10 year overall survival (OS), disease-free survival (DFS), and morbidity outcomes after SNR alone versus SNR + AD in SN negative patients.
- They also present updated data on the effect of occult metastases, found later in the SN by central, detailed pathologic analysis.
- 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group 1) or to SNR alone with AD only if SNs were positive (Group 2).
- 3,989 (71.1%) of 5,611 patients were SN negative, and 3,986 (99.9%) of these SN negative patients had follow-up information.
- 1,975 women had SNR + AD (Group 1) and 2,011 women had AD alone (Group 2).
- Median time on study was 9.4 years.
- Cox proportional hazard models adjusting for study stratification variables were used to compare OS and DFS between the two groups.
- Two-sided p values were used. HR values > 1 indicate a more favorable outcome in Group 1.
- Similar to the reported results at 8 years, there continues to be no significant difference in OS between patients who received SNR + AD versus SNR alone (HR: 1.11, p = 0.27) at 10 years.
- 10 year Kaplan-Meier (K-M) estimates for OS are 87.8% for SNR alone and 88.9% for SNR + AD.
- There continues to be no significant difference in DFS between the two groups (HR: 1.01, p=0.92).
- 10 year K-M estimates for DFS were 76.9% for both groups.
- There is also no significant difference in distant DFS between the two groups (HR: 1.09, p=0.29).
- There was no significant difference in the rates of local-regional recurrence between the two groups (HR: 1.09, p=0.29).
- The cumulative 10 year rates of local-regional recurrence with SNR + AD versus SNR alone were very low (4.3% versus 4.0%) and not significant (HR: 0.95, p = 0.77). Local (3.8% versus 3.3%), Axillary (0.2% versus 0.4%), Extra-axillary (0.3% versus 0.3%).
- Upon retrospective central pathology review, occult nodal disease was detected in 616 of 3,884 patients (15.8%) that were SN negative on initial H and E analysis. 430 (11.1%) had isolated tumor-cell clusters, 172 (4.4%) had micrometastases, and 14 (0.4%) had macrometastasis.
- Comparisons between the groups with and without occult disease yielded an adjusted HR for OS: 1.25 (p = 0.08) with an absolute difference at 10 years of 2.8% and a HR for DFS: 1.24 (p = 0.018) with an absolute difference of 4.1%.
- At 10 years there continues to be no significant differences in OS, DFS, distant DFS, or local-regional control between SNR and SNR + AD in patients with negative SN.
- SNR alone for clinically node negative breast cancer patients is a safe and effective method for axillary staging.
- For a subset of patients with occult metastases upon central pathology review, there is no significant difference in OS between this group and the group without occult metastases.
- For a subset of patients with occult metastases upon central pathology review, there is an absolute difference of 4.7% in DFS that is statistically significant.
- However, the impact of occult metastatic nodal disease on OS and DFS of this very large cohort of 5611 patients is non significant.
- The authors presented a 10 year update on a well performed phase III randomized study to determine whether a less invasive SNR can be substituted for a more aggressive AD without compromising survival and regional control in women with clinically node negative breast cancer.
- The results show that SNR should serve as the standard of care over AD in clinically node negative breast cancer as it provides equivalent OS and DFS while minimizing morbidity.
- The routine use of IHC analysis to detect occult disease in SN is likely unnecessary, as occult metastases did not impact OS in this cohort. Until now, physicians have been unsure about methods for managing patients with IHC-detected metastases. This data supports that treatment of these patients should be similar to that for patients with completely negative sentinel nodes.
November 26, 2012
November 25, 2015