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- Matikas, A., et al.
(författare)
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Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
- 2021
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Ingår i: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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- Matikas, A., et al.
(författare)
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Immune function and response to neoadjuvant chemotherapy in hormone receptor positive, HER2-negative breast cancer
- 2017
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundGene expression (GE) signatures and Tumor Infiltrating Lymphocyte (TILs) enumeration have shown promise as predictors of response to neoadjuvant chemotherapy in Hormone Receptor negative (HR-) and HER2+, but not in HR+/HER2- breast cancer (BC). This study aimed to explore their predictive value in HR+/HER2- BC, based on previous work from our group on the association of immune function and chemosensitivity in advanced HR+ BC.MethodsThe PROMIX phase 2 trial enrolled patients with locally advanced HER2- BC to receive six cycles of epirubicin and docetaxel, plus bevacizumab during cycles 3-6. Patients underwent tumor biopsies at baseline and after cycle 2 for GE profiling using DNA microarrays and TIL enumeration according to standard guidelines. Since pathologic complete remission (pCR) is relatively rare in HR+ BC, we also associated an immune gene module score (IMS) and TIL counts with the non-dichotomous variable of decrease in tumor size.ResultsOf the 150 enrolled patients, n = 113 were HR+. For n = 71, both TIL and GE data were available at baseline, while for n = 78 and n = 49 patients longitudinal TIL and GE data at baseline and cycle 2 were available, respectively. At baseline, on both univariate (OR = 2.29, P = 0.037) and multivariate analysis (OR = 2.35, P = 0.044) IMS was associated with pCR, while its association with tumor shrinkage was only apparent on univariate (P = 0.047) and not multivariate analysis (P = 0.061). TIL infiltration >50% (n = 9) was associated with neither pCR (OR = 1.812, P = 0.61) nor tumor shrinkage (P = 0.99). However, decreases in TIL counts in cycle 2 compared with baseline were associated with lesser decreases in tumor size (P = 0.043 for univariate and P = 0.044 for multivariate analysis).
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- Chretien, S, et al.
(författare)
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Beyond PD-1/PD-L1 Inhibition: What the Future Holds for Breast Cancer Immunotherapy
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cancer immunotherapy has altered the management of human malignancies, improving outcomes in an expanding list of diseases. Breast cancer - presumably due to its perceived low immunogenicity - is a late addition to this list. Furthermore, most of the focus has been on the triple negative subtype because of its higher tumor mutational load and lymphocyte-enriched stroma, although emerging data show promise on the other breast cancer subtypes as well. To this point the clinical use of immunotherapy is limited to the inhibition of two immune checkpoints, Programmed Cell Death Protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4). Consistent with the complexity of the regulation of the tumor – host interactions and their lack of reliance on a single regulatory pathway, combinatory approaches have shown improved efficacy albeit at the cost of increased toxicity. Beyond those two checkpoints though, a large number of co-stimulatory or co-inhibitory molecules play major roles on tumor evasion from immunosurveillance. These molecules likely represent future targets of immunotherapy provided that the promise shown in early data is translated into improved patient survival in randomized trials. The biological role, prognostic and predictive implications regarding breast cancer and early clinical efforts on exploiting these immune-related therapeutic targets are herein reviewed.
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