التفاصيل البيبلوغرافية
| العنوان: |
Prospective comparison of Recurrence Score and different definitions of luminal subtypes by central pathology assessment of single markers in early breast cancer: results from the phase III WSG-planB Trial. |
| المؤلفون: |
Gluz, O., Kreipe, H. H., Kates, R. E., Christgen, M., Liedtke, C., Shak, S., Clemens, M., Salem, M., Liedtke, B., Aktas, B., Markmann, S., Uleer, C., Augustin, D., Thomssen, C., Nitz, U., Harbeck, N. |
| المصدر: |
Cancer Research. Dec2012 Meeting Abstracts, Vol. 72 Issue 24a, p597-598. 2p. |
| مصطلحات موضوعية: |
*BREAST cancer research, *CANCER patients, *CANCER chemotherapy, *TUMORS, *DRUG therapy |
| مستخلص: |
Background: Routine use of multigene RT-PCR based assays as Recurrence Score (RS) vs. single markers (grade, uPA/PAI-1, HR, HER2, Ki-67) is controversially discussed in early BC. Several definitions of luminal A/B subtypes have been proposed by St. Gallen guidelines and individual researchers (grade 1/2 vs. 3, Ki-67 cut-offs 14 or 20%). Recently, integration of PR>20% was proposed as an immunhistochemical luminal A subtype definition (Ki-67<14%). Here, we present the final WSG-planB trial correlation analysis of risk assessment tools and the first prospective comparison of central and local pathology IHC/FISH assessment, RT-PCR for single markers, impact of central/local grade regarding allocation of patients to luminal A/B subtypes. Methods: planB trial (04/09 to 11/11: n=2,449 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2-BC; n=3197 registered; n=3072 available for central tumor bank). RS was used as selection criterion for chemotherapy (CTx) omission in HR+ BC (if RS<11 in pN0/pN1). Risk assessment by grade, HR, HER2 (IHC/FISH), Ki-67 was evaluated locally and centrally by an independent trial pathologist in all tumors. Clinical risk was estimated using AdjuvantOnline 8.0 (cut-off of 88% of breast cancer specific survival after 10 years without therapy in HR+ disease). Results: RS distribution in 2569 HR+ tumors: 0-11 (18%), 12-25 (60%), >25 (22%) (RS1853%/34%/13%). Luminal A subtype based on Ki-67 cut-off of <14%/<20%: 50.4%/68.8%. If PR>20% was included in the luminal A/Ki-67<14% definition: 37.6%. Luminal A/B based on local/central grade: 79%/21%; 67.9%/32.1%. In 354 pN0-1 patients, CTx was omitted based on low RS (88% compliance). In this group, 62% were high-risk by clinical-pathological criteria. Allocation to luminal A/B subtypes based on local/central grade varied substantially: overall concordance was 72%, but 40% of locally luminal B (HR+/G3) were luminal A (HR+/G1/2) by central and 60% of centrally luminal B were luminal A locally. Moderate correlations were found between RS and central grade (Spearman correlation rs=0.317; p < 0.001), local grade (0.321; p < 0.001) and Ki-67 (rs = 0.374; p < 0.001), particularly due to poor correlations in the RS group <26. Correlations between groups were: RS12 and luminal A/B Ki-6714 (rs = 0.26; p < 0.001). Inclusion of PR>20% moderately improved the correlation between luminal subtypes and RS to rs=0.34; p < 0.001. Data on allocation to luminal subtypes by local/central Ki-67 will be presented at the meeting. Conclusions: Our results represent the first prospective correlation of different luminal A/B definitions vs. a guideline mentioned gene signature (RS). High RS usually implies high grade and luminal B classification, the converse is not true. There is substantial heterogeneity in risk assessment by luminal A/B classification and grade in low/intermediate RS groups. Concordance for central/local assessment of grade and luminal A/B status was limited. There is strong need for standardization of molecular subtype's immunhistochemical/clinical definition prior to implementation into daily routine. Clinical significance of these findings will be addressed by further follow up of the WSG-planB trial. [ABSTRACT FROM AUTHOR] |
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