Gnant, M., Sestak, I., Filipits, M., Dowsett, M., Balic, M., Lopez-Knowles, E., Greil, R., Dubsky, P., Stoeger, H., Rudas, M., Jakesz, R., Ferree, S., Cowens, J. W., Nielsen, T., Schaper, C., Fesl, C., Cuzick, J. (2015) Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype. ANNALS OF ONCOLOGY, 26 (8). pp. 1685-1691. ISSN 0923-7534

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Abstract

Background: In the adjuvant treatment of hormone receptor-positive (HR+) breast cancer, variables like tumour size, grade and nodal status have great impact on therapy decisions. As most node-positive patients with HR+ breast cancer currently receive adjuvant chemotherapy improved methods for characterization of individuals' metastasis risk are needed to reduce overtreatment. Patients and methods: Tissue specimens from node-positive patients of the ABCSG-8 and ATAC trials who received adjuvant tamoxifen and/or anastrozole were included in this study. Analysing RNA from paraffin blocks using the PAM50 test, the primary objective was to evaluate the prognostic information of the risk of recurrence (ROR) score added to combined clinical standard variables in patients with one positive node (1N+) and in patients with two or three positive nodes (2-3N+), using log-likelihood ratio tests. Results: At a median follow-up of 9.6 years, distant metastases occurred in 97 (18%) of 543 node-positive patients. In a multivariate analysis, the PAM50-derived ROR score provided reliable prognostic information in addition to and beyond established clinical factors for 1N+ (P < 0.0001) and 2-3N+ patients (P = 0.0002). Ten-year distant recurrence risk was significantly increased in the high-risk compared with the low-risk group derived from ROR score for 1N+ [25.5%, 95% confidence interval (CI) 17.5% to 36.1% versus 6.6%, 95% CI 3.3% to 12.8%] and compared with the combined low/intermediate risk group for 2-3N+ patients (33.7%, 95% CI 25.5% to 43.8% versus 12.5%, 95% CI 6.6% to 22.8%). Additionally, the luminal A intrinsic subtype (IS) exhibited significantly lower risk of distant recurrence compared with the luminal B subtype in 1N+ and 2-3N+ patients. Conclusion: PAM50 ROR score and IS can identify node-positive patient subgroups with limited risk of metastasis after endocrine therapy, for whom adjuvant chemotherapy can be spared. The PAM50 test is a valuable tool in determining treatment of node-positive early-stage breast cancer patients.

Item Type:	Article
Authors (ICR Faculty only):	Dowsett, Mitch
All Authors:	Gnant, M., Sestak, I., Filipits, M., Dowsett, M., Balic, M., Lopez-Knowles, E., Greil, R., Dubsky, P., Stoeger, H., Rudas, M., Jakesz, R., Ferree, S., Cowens, J. W., Nielsen, T., Schaper, C., Fesl, C., Cuzick, J.
Additional Information:	ISI Document Delivery No.: CO7BI Times Cited: 1 Cited Reference Count: 17 Gnant, M. Sestak, I. Filipits, M. Dowsett, M. Balic, M. Lopez-Knowles, E. Greil, R. Dubsky, P. Stoeger, H. Rudas, M. Jakesz, R. Ferree, S. Cowens, J. W. Nielsen, T. Schaper, C. Fesl, C. Cuzick, J. AstraZeneca The original clinical trials were partly supported by AstraZeneca. Additional follow-up, re-consent procedures, and database maintenance was supported by NanoString Technologies (no grant number). 1 OXFORD UNIV PRESS OXFORD ANN ONCOL
Uncontrolled Keywords:	early-stage breast cancer (EBC) node-positive patients multigenomic testing prognostic subtypes risk of recurrence (ROR) intrinsic subtype (IS) DISTANT RECURRENCE TAMOXIFEN ANASTROZOLE PREDICTOR TRIAL Oncology
Research teams:	ICR divisions > Breast Cancer Research > Endocrinology ICR divisions > Molecular Pathology > Endocrinology
Depositing User:	Users 11 not found.
Date Deposited:	04 Sep 2015 09:45
Last Modified:	04 Sep 2015 09:45
URI:	http://publications.icr.ac.uk/id/eprint/14358

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