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- Johansson, Annelie, et al.
(författare)
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Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial
- 2022
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 40:35, s. 4071-4082
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSETo assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer.METHODSSecondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years.RESULTSIn estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit.CONCLUSIONThis study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.
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| 2. |
- Skoog, Annelie, et al.
(författare)
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Decoupling of total organic carbon concentrations and humic substance fluorescence in a an extended temperate estuary
- 2011
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Ingår i: Marine Chemistry. - 0304-4203. ; 124:1-4, s. 68-77
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Tidskriftsartikel (refereegranskat)abstract
- We present the first complete sections of humic substance fluorescence (HSfl)-values and total organic carbon (TOC) concentrations through the extended estuary of the Baltic Sea, Kattegat, and Skagerrak. Both HSfl-values and TOC concentrations correlated strongly with salinity, indicating terrestrial runoff as the main source for both components. However, their distributions do not result from a simple two end-member mixing and the two pools have different controls. In the Baltic Sea, surface water HSfl-values decreased from north to south, while TOC concentrations remained relatively constant, indicating an increasingly biologically-labile TOC pool from north to south. Both HSfl-values and TOC concentrations decreased strongly from the Baltic Sea to Kattegatt and Skagerrak. There were no major net sources or sinks for HSfl or TOC in Kattegat. However, the Jutland Current was an HSfl and TOC source for Skagerrak, probably derived from Danish rivers. Fraction of forested area in drainage basins of the Baltic Sea correlated positively with HSfl-values in freshwater end-members, but not with TOC concentrations. Land-runoff-volume relative to basin volume correlated positively with HSfl-values in surface waters, but not with TOC concentrations. In the Baltic Proper, deepwater oxygen concentrations correlated negatively with HSfl-values, indicating a significant source for HSfl (but not TOC) in suboxic and anoxic deepwaters. Photobleaching decreased HSfl-values in surface waters of the Baltic Proper, but had no effect on TOC concentrations. Despite terrestrial material being the main source for both TOC and HS, differences in control mechanisms result in a partial decoupling of their concentrations within the estuary.
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