| 1. |
- 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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| 2. |
- Colleoni, M., et al.
(författare)
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Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00
- 2016
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 34:28, s. 3400-9
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population. (C) 2016 by American Society of Clinical Oncology.
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| 3. |
- Metcalfe, Daniel B., et al.
(författare)
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Patchy field sampling biases understanding of climate change impacts across the Arctic
- 2018
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Ingår i: Nature Ecology and Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:9, s. 1443-1448
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Tidskriftsartikel (refereegranskat)abstract
- Effective societal responses to rapid climate change in the Arctic rely on an accurate representation of region-specific ecosystem properties and processes. However, this is limited by the scarcity and patchy distribution of field measurements. Here, we use a comprehensive, geo-referenced database of primary field measurements in 1,840 published studies across the Arctic to identify statistically significant spatial biases in field sampling and study citation across this globally important region. We find that 31% of all study citations are derived from sites located within 50 km of just two research sites: Toolik Lake in the USA and Abisko in Sweden. Furthermore, relatively colder, more rapidly warming and sparsely vegetated sites are under-sampled and under-recognized in terms of citations, particularly among microbiology-related studies. The poorly sampled and cited areas, mainly in the Canadian high-Arctic archipelago and the Arctic coastline of Russia, constitute a large fraction of the Arctic ice-free land area. Our results suggest that the current pattern of sampling and citation may bias the scientific consensuses that underpin attempts to accurately predict and effectively mitigate climate change in the region. Further work is required to increase both the quality and quantity of sampling, and incorporate existing literature from poorly cited areas to generate a more representative picture of Arctic climate change and its environmental impacts.
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| 4. |
- 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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