Combination of anthracyclines and anti-CD47 therapy inhibit invasive breast cancer growth while preventing cardiac toxicity by regulation of autophagy |
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Authors: | Yismeilin R. Feliz-Mosquea,Ashley A. Christensen,Adam S. Wilson,Brian Westwood,Jasmina Varagic,Giselle C. Meléndez,Anthony L. Schwartz,Qing-Rong Chen,Lesley Mathews Griner,Rajarshi Guha,Craig J. Thomas,Marc Ferrer,Maria J. Merino,Katherine L. Cook,David R. Soto-Pantoja |
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Affiliation: | 1.National Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP Legacy trials are now a part of the NRG Oncology portfolio),Pittsburgh,USA;2.UF Health Cancer Center at Orlando Health,Orlando,USA;3.NRG Oncology and the University of Pittsburgh,Pittsburgh,USA;4.Yonsei University College of Medicine,Seoul,South Korea;5.Genomic Health, Inc,Redwood City,USA;6.Allegheny Cancer Center at Allegheny General Hospital,Pittsburgh,USA |
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Abstract: | BackgroundThe 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen.MethodsThe B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years.ResultsIn univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72–1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69–1.47; p = 0.99), 0.84 (95% CI 0.62–1.14; p = 0.26), and 0.81 (95% CI 0.60–1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints.ConclusionsRS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28). |
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