SHON Expression Predicts Response and Relapse Risk of Breast Cancer Patients After Anthracycline-based Combination Chemotherapy or Tamoxifen Treatment

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aut.relation.endpage745
aut.relation.issue7en_NZ
aut.relation.journalBritish Journal of Canceren_NZ
aut.relation.startpage728
aut.relation.volume120en_NZ
aut.researcherLi, Yan
dc.contributor.authorAbdel-Fatah, TMAen_NZ
dc.contributor.authorBroom, RJen_NZ
dc.contributor.authorLu, Jen_NZ
dc.contributor.authorMoseley, PMen_NZ
dc.contributor.authorHuang, Ben_NZ
dc.contributor.authorLi, Len_NZ
dc.contributor.authorLiu, Sen_NZ
dc.contributor.authorChen, Len_NZ
dc.contributor.authorMa, RZen_NZ
dc.contributor.authorCao, Wen_NZ
dc.contributor.authorWang, Xen_NZ
dc.contributor.authorLi, Yen_NZ
dc.contributor.authorPerry, JKen_NZ
dc.contributor.authorAleskandarany, Men_NZ
dc.contributor.authorNolan, CCen_NZ
dc.contributor.authorRakha, EAen_NZ
dc.contributor.authorLobie, PEen_NZ
dc.contributor.authorChan, SYTen_NZ
dc.contributor.authorEllis, IOen_NZ
dc.contributor.authorHwang, LAen_NZ
dc.contributor.authorLane, DPen_NZ
dc.contributor.authorGreen, ARen_NZ
dc.contributor.authorLiu, DXen_NZ
dc.date.accessioned2022-07-29T03:36:48Z
dc.date.available2022-07-29T03:36:48Z
dc.date.copyright2019en_NZ
dc.date.issued2019en_NZ
dc.description.abstractBackground: SHON nuclear expression (SHON-Nuc + ) was previously reported to predict clinical outcomes to tamoxifen therapy in ERα + breast cancer (BC). Herein we determined if SHON expression detected by specific monoclonal antibodies could provide a more accurate prediction and serve as a biomarker for anthracycline-based combination chemotherapy (ACT). Methods: SHON expression was determined by immunohistochemistry in the Nottingham early-stage-BC cohort (n = 1,650) who, if eligible, received adjuvant tamoxifen; the Nottingham ERα − early-stage-BC (n = 697) patients who received adjuvant ACT; and the Nottingham locally advanced-BC cohort who received pre-operative ACT with/without taxanes (Neo-ACT, n = 120) and if eligible, 5-year adjuvant tamoxifen treatment. Prognostic significance of SHON and its relationship with the clinical outcome of treatments were analysed. Results: As previously reported, SHON-Nuc + in high risk/ERα + patients was significantly associated with a 48% death risk reduction after exclusive adjuvant tamoxifen treatment compared with SHON-Nuc − [HR (95% CI) = 0.52 (0.34–0.78), p = 0.002]. Meanwhile, in ERα − patients treated with adjuvant ACT, SHON cytoplasmic expression (SHON-Cyto + ) was significantly associated with a 50% death risk reduction compared with SHON-Cyto − [HR (95% CI) = 0.50 (0.34–0.73), p = 0.0003]. Moreover, in patients received Neo-ACT, SHON-Nuc − or SHON-Cyto + was associated with an increased pathological complete response (pCR) compared with SHON-Nuc + [21 vs 4%; OR (95% CI) = 5.88 (1.28–27.03), p = 0.012], or SHON-Cyto − [20.5 vs. 4.5%; OR (95% CI) = 5.43 (1.18–25.03), p = 0.017], respectively. After receiving Neo-ACT, patients with SHON-Nuc + had a significantly lower distant relapse risk compared to those with SHON-Nuc − [HR (95% CI) = 0.41 (0.19–0.87), p = 0.038], whereas SHON-Cyto + patients had a significantly higher distant relapse risk compared to SHON-Cyto − patients [HR (95% CI) = 4.63 (1.05–20.39), p = 0.043]. Furthermore, multivariate Cox regression analyses revealed that SHON-Cyto + was independently associated with a higher risk of distant relapse after Neo-ACT and 5-year tamoxifen treatment [HR (95% CI) = 5.08 (1.13–44.52), p = 0.037]. The interaction term between ERα status and SHON-Nuc + (p = 0.005), and between SHON-Nuc + and tamoxifen therapy (p = 0.007), were both statistically significant. Conclusion: SHON-Nuce + in tumours predicts response to tamoxifen in ERα + BC while SHON-Cyto + predicts response to ACT.en_NZ
dc.identifier.citationBritish Journal of Cancer 120, 728–745 (2019). https://doi.org/10.1038/s41416-019-0405-x
dc.identifier.doi10.1038/s41416-019-0405-xen_NZ
dc.identifier.issn0007-0920en_NZ
dc.identifier.issn1532-1827en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/15328
dc.publisherSpringer Nature
dc.relation.urihttps://www.nature.com/articles/s41416-019-0405-x
dc.rights© 2019, Cancer Research UK. This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.accessrightsOpenAccessen_NZ
dc.subjectMolecular medicine; Predictive markers; Prognostic markers
dc.titleSHON Expression Predicts Response and Relapse Risk of Breast Cancer Patients After Anthracycline-based Combination Chemotherapy or Tamoxifen Treatmenten_NZ
dc.typeJournal Article
pubs.elements-id354783
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Faculty of Health & Environmental Science
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/School of Public Health & Interdisciplinary Studies
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/School of Public Health & Interdisciplinary Studies/Biosciences Department
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/School of Science
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/School of Science/Biomedicine & Medical Diagnostics Department
pubs.organisational-data/AUT/PBRF
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences/HA Science 2018 PBRF
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences/HI Interprofessional 2018 PBRF
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