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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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- 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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- Tobin, N. P., et al.
(författare)
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Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 26:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and beta-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and beta-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3-10.9] and HER2-enriched (HR 4.4; 95% CI 1.5-12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B, and 5% normal-like. We show that tumor characteristics and molecular subtypes of breast cancer metastases significantly influence post-relapse patient survival, emphasizing that molecular investigations at relapse provide prognostic and clinically relevant information.
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