| 1. |
- Kimbung, Siker, et al.
(författare)
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CYP27A1 expression is associated with risk of late lethal estrogen receptor-positive breast cancer in postmenopausal patients
- 2020
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: 27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. Methods: Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemistry in two Swedish population-based cohorts (n = 645 and n = 813, respectively). Cox proportional hazards models were used to evaluate the association between CYP27A1 expression and prognosis. Results: CYP27A1 was highly expressed in less than 1/3 of the tumors. High CYP27A1 expression was more frequent among high-grade tumors lacking hormone receptor expression and with larger tumor sizes. Over a median of 12.2 years follow-up in cohort 1, high CYP27A1 expression was associated with impaired survival, specifically after 5 years from diagnosis among all patients [overall survival (OS), HRadjusted = 1.93, 95%CI = 1.26–2.97, P = 0.003; breast cancer-specific survival (BCSS), HRadjusted = 2.33, 95%CI = 1.28–4.23, P = 0.006] and among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 1.99, 95%CI = 1.24–3.21, P = 0.004; BCSS, HRadjusted = 2.78, 95%CI = 1.41–5.51, P = 0.003]. Among all patients in cohort 2 (median follow-up of 7.0 years), CYP27A1 expression was significantly associated with shorter OS and RFS in univariable analyses across the full follow-up period. However after adjusting for tumor characteristics and treatments, the association with survival after 5 years from diagnosis was non-significant among all patients [OS, HRadjusted = 1.08, 95%CI = 0.05–2.35, P = 0.83 and RFS, HRadjusted = 1.22, 95%CI = 0.68–2.18, P = 0.50] as well as among patients ≥ 55 years presenting with ER+ tumors [OS, HRadjusted = 0.46 95% CI = 0.11–1.98, P = 0.30 and RFS, HRadjusted = 0.97 95% CI = 0.44–2.10, P = 0.93]. Conclusion: CYP27A1 demonstrated great potentials as a biomarker of aggressive tumor biology and late lethal disease in postmenopausal patients with ER+ BC. Future studies should investigate if the benefits of prolonged endocrine therapy and cholesterol-lowering medication in BC are modified by CYP27A1 expression.
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| 2. |
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| 3. |
- Rosendahl, Ann H., et al.
(författare)
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Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence : A Nested Case-Control Study
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IRm) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted Ptrend=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted Ptrend=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IRm positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IRm positive tumors but not in those with IGF-IRm negative tumors (Pinteraction=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER+ tumors. Postoperative changes >10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.
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| 4. |
- Tryggvadottir, Helga, et al.
(författare)
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The impact of body size changes on recurrence risk depends on age and estrogen receptor status in primary breast cancer
- 2019
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Ingår i: Cancer causes & control : CCC. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 30:11, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the prognostic impact of body size changes during the first postoperative year in breast cancer. METHODS: A cohort of 1,317 primary breast cancer patients included in Sweden (2002-2014) underwent body size measurements at the preoperative and 1-year visits (n = 1,178). Landmark survival analyses were used to investigate how postoperative weight gain or loss (> 5%) or change in waist-hip ratio (WHR) categories (≤ 0.85 or > 0.85) impact prognosis. RESULTS: Median age at inclusion was 61 years and body mass index 25.1 kg/m2. After a median follow-up of 5.0 years from inclusion, 165 recurrences and 77 deaths occurred. Weight gain (17.0%) conferred over twofold recurrence risk only in patients < 50 years (Pinteraction = 0.033). Weight loss (8.6%) was only associated with a poor prognosis in patients ≥ 70 years, but not after restriction analysis. Weight change did not impact prognosis in patients 50 to < 70 years. Changes between WHR categories were associated with differential recurrence risk depending on estrogen receptor (ER) status (Pinteraction = 0.007), with higher recurrence risk in patients with ER+ tumors and lower recurrence risk with ER- tumors. CONCLUSION: Both changes in terms of weight and WHR category yielded independent prognostic information. Further research is imperative before recommending weight loss for all overweight breast cancer patients.
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| 5. |
- Tryggvadottir, Helga, et al.
(författare)
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The Prognostic Impact of Intratumoral Aryl Hydrocarbon Receptor in Primary Breast Cancer Depends on the Type of Endocrine Therapy : A Population-Based Cohort Study
- 2021
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- The aryl hydrocarbon receptor (AhR) is a master regulator of multiple pathways involved in breast cancer, and influences the estrogen receptor alpha (ER) and aromatase/CYP19A1. The purpose of this study was to elucidate the interplay between intratumoral levels of AhR and aromatase, patient characteristics (including AhR and CYP19A1 genotypes), clinicopathological features, and prognosis in breast cancer patients receiving adjuvant treatments. A prospective cohort of 1116 patients with primary breast cancer in Sweden, included 2002–2012, was followed until June 30th 2019 (median 8.7 years). Tumor‐specific AhR (n=920) and aromatase levels (n=816) were evaluated on tissue microarrays using immunohistochemistry. Associations between cytoplasmatic (AhRcyt) and nuclear (AhRnuc) AhR levels, intratumoral aromatase, clinicopathological features, and prognosis in different treatment groups were analyzed. Low AhRcyt levels (n=183) and positive intratumoral aromatase (n=69) were associated with estrogen receptor (ER)– status and more aggressive tumors. Genotypes were not associated with their respective protein levels. The functional AhRArg554Lys GG genotype was associated with recurrence-free survival in switch-therapy (sequential tamoxifen/aromatase inhibitors (AI) or AI/tamoxifen) treated patients (HRadj 0.42; 95% CI 0.22–0.83). High AhRcyt levels were associated with longer recurrence-free survival during the first 10 years of follow-up among tamoxifen-only treated patients (HRadj 0.40; 95% CI 0.23–0.71) compared to low AhRcyt levels, whereas an almost inverse association was seen in patients with switch-therapy (Pinteraction=0.023). Intratumoral aromatase had little prognostic impact. These findings warrant confirmation in an independent cohort, preferably in a randomized clinical trial comparing different endocrine regimens. They might also guide the selection of breast cancer patients for clinical trials with selective AhR modulators.
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| 6. |
- Ygland Rödström, Maria, et al.
(författare)
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Acute Mania and Catatonia in a Teenager Successfully Treated with Electroconvulsive Therapy and Diagnosed with Turner Syndrome and Bipolar Disorder
- 2021
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Ingår i: Case Reports in Psychiatry. - : Hindawi Limited. - 2090-682X .- 2090-6838. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background. Turner syndrome (TS) is an X-linked chromosomal abnormality with a global prevalence of 1/2000 live-born girls. The physiological symptoms of TS have been thoroughly characterized, but only a few studies have described associated psychiatric symptoms. We report a case of an adolescent girl who presented with acute mania with psychotic features and was successfully treated with electroconvulsive therapy (ECT). She was subsequently diagnosed with bipolar syndrome and TS. Case Presentation. A 17-year-old girl presented to us with manic symptoms, including disorganized speech, auditory hallucinations, and affect lability. Initially, she was treated with antipsychotics and benzodiazepines, whereby the positive affective symptoms declined. However, the psychotic symptoms progressed, and she developed a catatonic state. ECT was started 6 days after admission, with improvement after two treatments. When ECT was tapered after seven sessions, she relapsed, and the treatment was extended to twelve sessions, with successful outcome. Following discharge, she was diagnosed with TS with partial loss on one of the X-chromosomes (46X, del (X)(p21)), which might have contributed to the development of her sudden acute manic episode. Conclusions. This case demonstrates for the first time that ECT may be a safe and efficient treatment strategy for acute mania in adolescents with concomitant TS and that severely affected adolescents may require a prolonged series with gradual tapering of ECT. The present case also demonstrates a possible association between TS and bipolar syndrome and that the clinical presentation of a manic episode in a patient with this comorbidity could be more complex and the treatment response slower.
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