P3-07-08: Accurate Staging of Axillary Lymph Nodes from Breast Cancer Patients Using a Novel Molecular Method.

Abstract

Abstract Background: In breast cancer, the number of axillary lymph node metastases is the powerful prognostic factor. However, it is obvious that conventional histopathological examinations are non-standardized and limited in their ability to detect metastases accurately due to the partial evaluation of a node. This may lead to underestimation of nodal staging. The one-step nucleic acid amplification (OSNA) assay was developed to overcome this limitation of the histopathological examination. This assay can assess the whole lymph node and yields semi-quantitative results for the detection of clinically relevant nodal metastases by detection and amplification of cytokeratin 19 mRNA. This assay can classify the nodes into 4 categories, (++), (+I), (+), and negative. (++) and (+I) are theoretically regarded as macrometastasis and (+) as micrometastasis according to the American Joint Committee on Cancer (AJCC) staging system. We have shown the OSNA whole node assay detects more sentinel node (SN) metastases, particularly micrometastases than 2-mm-section frozen-section histology. Thus, we had hypothesized that the OSNA assay for non-sentinel nodes (nonSNs) in addition to SNs enables the classification of accurate nodal staging for breast cancer patients. In the present retrospective cohort study, we compared the performance of the OSNA assay with that of routine permanent histology for the detection of nonSN metastases among patients with positive SN biopsy who have undergone axillary dissection. Patients and methods: Subjects comprised of consecutive 183 patients with clinically and ultrasonographically node-negative pT1-2 breast cancer who had undergone axillary dissection after positive SN biopsy with the OSNA assay between April 2009 and September 2010. Of these, for nonSN evaluation, 64 had single-section permanent histology while 119 patients underwent the OSNA whole node assay. We compared 1) detection rates of nonSN metastasis, including macro- and micrometastases and 2) upstaging rates from SN stage after the nonSN assessment according to the 7th AJCC staging system between both cohorts. We performed the two-population z test. Results: 1) NonSNs were found to be positive for metastasis more frequently in the OSNA cohort than in the histology cohort (histology 13/64, 20.3%, 95% CI 11.7−32.6% vs. OSNA 66/119, 55.5%, 95% CI 46.1−64.5%; P<0.001). We found no significant difference in the frequency of macrometastasis in nonSNs (12/64, 18.8%, 95% CI 10.5−30.8% vs. 30/119, 25.2%, 95% CI 17.9−34.2%; P=0.42). However, we found significant difference in the frequency of micrometastasis in nonSNs (1/64, 1.6%, 95% CI; 0.1−9.5% vs. 36/119, 30.3%, 95% CI; 22.3−39.5%; P<0.001). 2) Total upstaging rates were similar in both cohorts (histology 9/64, 14.1%, 95% CI 7.0−25.5% vs. OSNA 20/119, 16.8%, 95% CI 10.8−25.0%; P=0.79). Conclusion: The OSNA whole node assay detects a far greater proportion of nonSN metastases than single-section histology in patients with positive SN biopsy. However, in terms of the AJCC staging system, upstaging rates from the SN stage were similar in both cohorts. Follow-up of the OSNA cohort is required to clarify the prognostic implications of this technique; this may lead to the establishment of a new breast cancer staging. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-08.