| 21. |
- Phillips, K. A., et al.
(författare)
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Adjuvant ovarian function suppression and cognitive function in women with breast cancer
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 114:9, s. 956-964
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Tidskriftsartikel (refereegranskat)abstract
- Background: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer. Methods: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen + OFS, exemestane + OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score. Data were compared for the pooled tamoxifen + OFS and exemestane + OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test. Results: Of 86 participants, 74 underwent both T0 and T1 cognitive testing; 54 randomised to OFS+ either tamoxifen (28) or exemestane (26) and 20 randomised to tamoxifen alone. There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group (mean +/- s.d., -0.21 +/- 0.92 vs -0.04 +/- 0.49, respectively, P = 0.71, effect size = -0.20), regardless of prior chemotherapy status, and adjusting for baseline characteristics. Conclusions: The Co-SOFT study, although limited by small samples size, provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function.
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| 22. |
- Aebi, S, et al.
(författare)
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Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX
- 2011
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Ingår i: ANNALS OF ONCOLOGY. - 0923-7534. ; 22:9, s. 1981-1987
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Background: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)positive lymph node-negative breast cancer is being reassessed. Patients and methods: After stratification by ER status, 1669 postmenopausal patients with operable lymph nodenegative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF/tamoxifen) or to tamoxifen alone for 5 years. Results: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF/tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. Conclusion: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
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| 23. |
- Karlsson, Per, 1963, et al.
(författare)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
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Tidskriftsartikel (refereegranskat)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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| 24. |
- Rabaglio, M, et al.
(författare)
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Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.
- 2009
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 1569-8041. ; 20:9, s. 1489-98
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.
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| 25. |
- Tin, A, et al.
(författare)
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Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7173-
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Tidskriftsartikel (refereegranskat)abstract
- Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
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| 26. |
- Wallgren, Arne, 1940, et al.
(författare)
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Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII.
- 2003
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 21:7, s. 1205-13
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. PATIENTS AND METHODS: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. RESULTS: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. CONCLUSION: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size.
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| 27. |
- Jerusalem, G, et al.
(författare)
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Continuous versus intermittent extended adjuvant letrozole for breast cancer: Final results of randomized phase 3 SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.
- 2021
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 32:10, s. 1256-1266
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Tidskriftsartikel (refereegranskat)abstract
- Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy. In animal models, resistance was reversed with restoration of circulating estrogen level during interruption of letrozole treatment. This phase 3 randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen sub-study (SOLE-EST) analyzed the level of estrogen during the interruption of treatment.SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant endocrine therapy. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day during 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all year 5).Intention-to-treat population included 4851 women in SOLE (n=2425 in intermittent and n=2426 in continuous letrozole groups) and 103 women in SOLE-EST (n=78 in intermittent and n=25 in continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival was 81.4% in intermittent group and 81.5% in continuous group (hazard ratio: 1.03, 95%CI: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment.Extended adjuvant endocrine therapy by intermittent administration of letrozole did not improve disease-free survival compared to continuous use despite the recovery of circulating estrogen level. The similar disease-free survival coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.
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| 28. |
- Pestalozzi, B. C., et al.
(författare)
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Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup phase III BIG 02-98 trial
- 2008
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 19:11, s. 1837-1841
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Tidskriftsartikel (refereegranskat)abstract
- Background: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. Patients and methods: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG 02-98 trial comparing anthracycline-based adjuvant chemotherapy (control arms) to anthracycline-docetaxel-based sequential or concurrent chemotherapy (experimental arms). After a median follow-up of 5 years, 403 patients had died and detailed information on CNS relapse was collected for these patients. Results: CNS relapse occurred in 4.0% of control patients and3.7% of docetaxel-treated patients. CNS relapse occurred in 27% of deceased patients in both treatment groups. CNS relapse was usually accompanied by neurologic symptoms (90%), and 25% of patients with CNS relapse died without evidence of extra-CNS relapse. Only 20% of patients survived 1 year from the diagnosis of CNS relapse. Prognosis of CNS relapse was worse for patients with meningeal carcinomatosis when compared with brain metastases. Unexpected findings included a higher rate of positive cerebrospinal fluid cytology (8% versus 3%) and more frequent use of magnetic resonance imaging for diagnosis (47% versus 30%) in the docetaxel-treated patients. Conclusion: There is no evidence that adjuvant docetaxel treatment is associated with an increased frequency of CNS relapse. © The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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