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Age-specific trends of survival in metastatic breast cancer: 26 years longitudinal data from a population-based cancer registry in Stockholm, Sweden.

https://arctichealth.org/en/permalink/ahliterature101025
Source
Breast Cancer Res Treat. 2011 May 27;
Publication Type
Article
Date
May-27-2011
Author
Theodoros Foukakis
Tommy Fornander
Tobias Lekberg
Henrik Hellborg
Jan Adolfsson
Jonas Bergh
Author Affiliation
Department of Oncology-Pathology, Radiumhemmet, Karolinska Institutet, Karolinska University Hospital, 17176, Stockholm, Sweden, theodoros.foukakis@ki.se.
Source
Breast Cancer Res Treat. 2011 May 27;
Date
May-27-2011
Language
English
Publication Type
Article
Abstract
Treatment of metastatic breast cancer (MBC) has evolved during the last decades but it is largely unknown whether this has led to improved survival in the general MBC population. Based on the regional, population-based breast cancer registry, we identified 5,463 patients diagnosed with MBC in Stockholm County during 1979-2004. Patients were divided into five cohorts based on the year of first MBC diagnosis and observed and relative survival were compared across the cohorts after adjustment for potential confounders. A significant trend of better survival over time was demonstrated for patients 60 years or younger (P 
PubMed ID
21617918 View in PubMed
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Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.

https://arctichealth.org/en/permalink/ahliterature277996
Source
JAMA. 2016 Nov 08;316(18):1888-1896
Publication Type
Article
Date
Nov-08-2016
Author
Theodoros Foukakis
Gunter von Minckwitz
Nils-Olof Bengtsson
Yvonne Brandberg
Birgitta Wallberg
Tommy Fornander
Brigitte Mlineritsch
Sabine Schmatloch
Christian F Singer
Günther Steger
Daniel Egle
Eva Karlsson
Lena Carlsson
Sibylle Loibl
Michael Untch
Mats Hellström
Hemming Johansson
Harald Anderson
Per Malmström
Michael Gnant
Richard Greil
Volker Möbus
Jonas Bergh
Source
JAMA. 2016 Nov 08;316(18):1888-1896
Date
Nov-08-2016
Language
English
Publication Type
Article
Keywords
Adult
Aged
Antibiotics, Antineoplastic - administration & dosage - adverse effects
Antineoplastic Agents - administration & dosage - adverse effects - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - administration & dosage - adverse effects - therapeutic use
Austria
Breast Neoplasms - drug therapy - mortality - pathology
Chemotherapy, Adjuvant - adverse effects - methods
Cyclophosphamide - administration & dosage
Disease-Free Survival
Drug Administration Schedule
Epirubicin - administration & dosage
Female
Fluorouracil - administration & dosage
Germany
Humans
Middle Aged
Neoplasm Recurrence, Local
Quality of Life
Sweden
Taxoids - administration & dosage
Abstract
Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy.
To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule.
A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011.
Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks.
The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects.
Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (=1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P?=?.06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0.63-0.99; P?=?.04; 5-year EFS, 86.7% vs 82.1%). The groups did not differ in OS (HR, 0.77; 95% CI, 0.57-1.05; P?=?.09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95% CI, 0.64-1.08; P?=?.17; 5-year DDFS, 89.4% vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group.
Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group.
clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.
Notes
Comment In: JAMA. 2016 Nov 8;316(18):1877-187827723886
PubMed ID
27825007 View in PubMed
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Ki67 measured in metastatic tissue and prognosis in patients with advanced breast cancer.

https://arctichealth.org/en/permalink/ahliterature263001
Source
Breast Cancer Res Treat. 2014 Sep;147(2):407-14
Publication Type
Article
Date
Sep-2014
Author
Claudette Falato
Julie Lorent
Edneia Tani
Eva Karlsson
Paul K Wright
Jonas Bergh
Theodoros Foukakis
Source
Breast Cancer Res Treat. 2014 Sep;147(2):407-14
Date
Sep-2014
Language
English
Publication Type
Article
Keywords
Breast Neoplasms - metabolism - pathology
Female
Humans
Kaplan-Meier Estimate
Ki-67 Antigen - metabolism
Middle Aged
Neoplasm Metastasis
Neoplasm Recurrence, Local - metabolism - pathology
Prognosis
Retrospective Studies
Sweden
Abstract
The purpose of this study is to determine the prognostic role of Ki67 evaluated in relapse biopsies from patients with metastatic breast cancer (MBC). Two hundred and ten patients diagnosed with MBC in Stockholm, Sweden between 1998 and 2009 and with Ki67 assessed at time of first systemic relapse (mKi67) were retrospectively identified and divided into two groups according to mKi67 fraction (low =20 %, high >20 %). Post-relapse survival was compared between the groups using Kaplan-Meier and Cox regression methods. Death rate as function of continuous mKi67 was also evaluated. Furthermore, the prognostic role of intra-individual change in Ki67 between primary tumor and matched metastasis was explored by Kaplan-Meier plots. One hundred and twenty-five patients had low and 85 had high mKi67. Median survival was 25 and 17 months in low- and high-mKi67 group, respectively [hazard ratio (HR) 0.69, 95 % confidence intervals (CI) 0.51-0.92, P = 0.01]. In a multivariate model adjusted for prognostic confounders, low-mKi67 showed a non-significant trend toward better survival (HR 0.85, 95 %CI 0.62-1.16, P = 0.30). Nevertheless, mKi67 independently correlated with survival when compared with primary tumor proliferation (HR 0.56, 95 %CI 0.38-0.81, P = 0.002). The 2-year death rate steeply increased as mKi67 increased. Moreover, the change from high in primary tumor to low in metastasis significantly correlated with longer survival when compared with stable Ki67 levels (HR 0.48, 95 %CI 0.31-0.76, P = 0.002). In this cohort of MBC patients, mKi67 inversely but not independently correlated with survival. However, a significant association between mKi67 and survival was shown regardless of primary tumor proliferation.
PubMed ID
25129344 View in PubMed
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A retrospective safety and efficacy analysis of the first patients treated with eribulin for metastatic breast cancer in Stockholm, Sweden.

https://arctichealth.org/en/permalink/ahliterature273067
Source
Acta Oncol. 2015 Apr;54(4):522-9
Publication Type
Article
Date
Apr-2015
Author
Luisa Kessler
Claudette Falato
Sara Margolin
Jonas Bergh
Theodoros Foukakis
Source
Acta Oncol. 2015 Apr;54(4):522-9
Date
Apr-2015
Language
English
Publication Type
Article
Keywords
Adult
Breast Neoplasms - drug therapy - metabolism - mortality - pathology
Disease-Free Survival
Drug Administration Schedule
Fatigue - chemically induced
Female
Furans - administration & dosage - adverse effects
Humans
Infection - chemically induced
Ketones - administration & dosage - adverse effects
Ki-67 Antigen - metabolism
Middle Aged
Neutropenia - chemically induced
Peripheral Nervous System Diseases - chemically induced
Receptor, ErbB-4 - metabolism
Receptors, Estrogen - metabolism
Retrospective Studies
Sweden
Tubulin Modulators - administration & dosage - adverse effects
Abstract
Eribulin is a non-taxane, microtubule dynamics inhibitor approved for the treatment of patients with metastatic breast cancer (MBC) in Europe in March 2011.
For the purpose of an internal quality control, all patients with MBC treated with eribulin at Karolinska University Hospital were registered in a database. Clinical data were collected retrospectively for patients that were registered by August 2012 and safety and efficacy of eribulin were evaluated. Treatment toxicity including fatigue, neurotoxicity and infection was graded according to CTCAE v4.0. Objective response to treatment was investigated using routinely performed radiological assessments. When only clinical assessments were made, the evaluation of the treating physician was used. Furthermore, the efficacy of eribulin was investigated in different tumor subtypes.
Forty-eight patients who received at least one cycle of eribulin were identified. Most patients were heavily pretreated with a median of 3 (range 1-7) previous chemotherapy lines prior to eribulin. Median patient age was 56 years (range 35-74). At the end of the analysis, 23 patients were alive and two were still treated with eribulin. No hypersensitivity reactions and no toxic deaths were seen. Fatigue grade 3-4 was observed in three patients (6.3%). One patient experienced grade 4 neurotoxicity. Grade 3-4 neutropenia was documented in 18.8%, and three patients were treated for a grade 3 infection. Interestingly, three individuals developed Herpes zoster reactivation. One patient responded to treatment with complete remission, while 33.3% had a partial response. 48% of all patients had a clinical benefit (objective response or stable disease for more than six months).
Eribulin administered outside of a clinical trial in patients with advanced breast cancer was safe and well tolerated. A clinical benefit was seen in half of the cases. No statistically significant differences in objective response or survival were observed between histopathological subgroups.
PubMed ID
25383448 View in PubMed
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