| 1. |
- Markkula, Andrea, et al.
(författare)
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Paternal intelligence affects school grades in children with and without ADHD - a register-based study
- 2024
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Ingår i: European Child and Adolescent Psychiatry. - 1018-8827 .- 1435-165X.
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Tidskriftsartikel (refereegranskat)abstract
- ADHD profoundly impacts educational attainment, quality of life, and health in young adults. However, certain subgroups of ADHD patients seem to do quite well, potentially due to differences in intelligence and socioeconomic status. Here we used paternal intelligence from the Swedish Defence Conscription and Assessment register, to investigate the role of genetic propensity for intelligence, on school performance in a large cohort of ADHD patients and matched controls. Patients treated for ADHD in Linköping, Sweden between 1995 and 2020 (n = 3262), sex- and age-matched controls (n = 9591) as well as their parents and siblings were identified using regional and national registers. Socioeconomic and demographic data, ADHD diagnosis and treatment and school grades at age 16 for the study population were extracted from Swedish National registers. We explored the associations between paternal intelligence and child school performance using linear mixed models and mediation analyses, taking a wide range of potential covariates into account. Results indicate that paternal intelligence was positively associated with standardized school grades in their offspring (Zadjusted=0.09, 95%CI 0.07, 0.10). This effect was present in both ADHD patients and controls, but ADHD patients had significantly lower standardized grades (Zadjusted=-1.03, 95%CI -1.08, -0.98). Child ADHD did not serve as a mediator for how paternal intelligence affected school grades. Our findings indicate that ADHD prevents children from reaching their academic potential at all levels of paternal intelligence. Increased understanding of the contributions of ADHD, intelligence, and SES to functional outcomes can help clinicians to better personalize interventions to the unique preconditions in each patient.
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| 2. |
- Björner, Sofie, et al.
(författare)
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Body mass index influences the prognostic impact of combined nuclear insulin receptor and estrogen receptor expression in primary breast cancer
- 2017
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 8:NOV
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor a (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER- tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR- tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR-/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR-/ER- tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER- tumors. Normal-weight patients with nuclear InsR-/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR-/ER- tumors may benefit from more tailored treatment or weight management.
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| 3. |
- Björner, Sofie, et al.
(författare)
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Combined and individual tumor-specific expression of insulinlike growth factor-I receptor, insulin receptor and phosphoinsulin- like growth factor-I receptor/insulin receptor in primary breast cancer : Implications for prognosis in different treatment groups
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:6, s. 9093-9107
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Tidskriftsartikel (refereegranskat)abstract
- Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection. Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a populationbased cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden. IGF1R (n = 923), InsR (n = 900), and pIGF1R/InsR (n = 904) combined cytoplasmic and membrane staining was dichotomized. IGF1Rstrong/InsRmod/strong/pIGF1R/InsRpos tumors were borderline associated with 2-fold risk for events, HRadj (2.00; 95%CI 0.96-4.18). Combined IGF1R and pIGF1R/InsR status only impacted prognosis in patients with InsRmod/strong expressing tumors (Pinteraction = 0.041). IGF1Rstrong expression impacted endocrine treatment response differently depending on patients' age and type of endocrine therapy. Phospho-IGF1R/InsRpos was associated with lower risk for events among non-endocrine-treated patients irrespective of ER status, HRadj (0.32; 95%CI 0.16-0.63), but not among endocrinetreated patients (Pinteraction = 0.024). In non-endocrine-treated patients, pIGF1R/InsRpos was associated with lower risk for events after radiotherapy, HRadj (0.31; 95%CI 0.12-0.80), and chemotherapy, HRadj (0.29; 95%CI 0.09-0.99). This study highlights the complexity of IGF hetero-and homodimer signaling network and its interplay with endocrine treatment, suggesting that combinations of involved factors may improve patient selection for IGF1R-targeted therapy.
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| 4. |
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| 5. |
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| 6. |
- Elebro, Karin, et al.
(författare)
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High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy-Treated Patients-Results from a Population-Based Breast Cancer Cohort
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:3, s. 766-777
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups.EXPERIMENTAL DESIGN: A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed.RESULTS: Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as >75% (ERβ175(+), 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ175(+) was associated with lower risk of breast cancer events [HRadj = 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ERα(-) tumors (HRadj = 0.30; 95% CI, 0.12-0.76), compared with ERα(+) tumors (HRadj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERβ175(+) tumors were associated with lower risk of breast cancer events compared with ERβ175(-) tumors (HRadj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERβ175 status was not associated with the outcome.CONCLUSION: High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 1-12. ©2016 AACR.
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| 7. |
- Gustbée, Emma, et al.
(författare)
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Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events.
- 2013
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Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Breast-feeding is a known protective factor against breast cancer. Breast-feeding duration is influenced by hormone levels, milk production, and lifestyle factors. The aims were to investigate how breast-feeding duration and milk production affected tumor characteristics and risk for early breast cancer events in primary breast cancer patients. Between 2002 and 2008, 634 breast cancer patients in Lund, Sweden, took part in an ongoing prospective cohort study. Data were extracted from questionnaires, pathology reports, and patients' charts from 592 patients without preoperative treatment. Breast-feeding duration ≤12 months of the first child was associated with higher frequency of ER+/PgR+ tumors (P=0.02). Median follow-up time was 4.9 years. Higher risk for early events was observed for breast-feeding duration of first child >12 months (LogRank P=0.001), total breast-feeding duration >12 months (LogRank P=0.008), as well as 'excessive milk production' during breast-feeding of the first child (LogRank P=0.001). Patients with 'almost no milk production' had no events. In a multivariable model including both 'excessive milk production' and breast-feeding duration of the first child >12 months, both were associated with a two-fold risk for early events, adjusted HRs 2.33 (95% CI: 1.25-4.36) and 2.39 (0.97-5.85), respectively, while total breast-feeding duration was not. 'Excessive milk production' was associated with a two-fold risk of early distant metastases, adjusted HR 2.59 (1.13-5.94), but not duration. In conclusion, 'excessive milk production' during breast-feeding was associated with higher risk for early events independent of tumor characteristics, stressing the need to consider host factors in the evaluation of prognostic markers.
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| 8. |
- Gustbée, Emma, et al.
(författare)
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Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients.
- 2015
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Ingår i: BMC Clinical Pathology. - : Springer Science and Business Media LLC. - 1472-6890. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS).
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| 9. |
- Huzell, Louise, et al.
(författare)
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History of oral contraceptive use in breast cancer patients: impact on prognosis and endocrine treatment response.
- 2015
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 149:2, s. 505-515
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to study oral contraceptive (OC) use in relation to breast cancer events and endocrine treatment response in a prospective population-based cohort, because it is unclear whether history of OC use impacts on prognosis in breast cancer patients. Between 2002 and 2011, 994 primary breast cancer patients without preoperative treatment were enrolled in Lund, Sweden and followed until December 2012. History of OC use was obtained from preoperative questionnaires. Tumor characteristics, clinical data, and date of death were obtained from pathology reports, patient charts, and population registries. Among the 948 patients with invasive cancer and no metastasis detected on the post-operative screen, 74 % had ever used OCs. Patients were followed for up to nine years (median follow-up 3 years), and 100 breast cancer events were recorded. Ever OC use was not associated with prognosis, irrespective of duration. However, any OC use before age 20 was associated with a threefold increased risk for breast cancer events in patients <50 years but not in patients ≥50 years (P interaction = 0.009). In patients ≥50 years with estrogen receptor positive tumors, previous OC use at any age was associated with a significantly decreased risk of breast cancer events among patients who received aromatase inhibitors compared to patients who never used OCs (adjusted HR 0.37: 95 % CI 0.15-0.87). OC use was not associated with tamoxifen-response. If confirmed, history of OC use may yield valuable prognostic and treatment predictive information in addition to currently used criteria.
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| 10. |
- Markkula, Andrea, et al.
(författare)
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Clinical Profiles Predict Early Nonadherence to Adjuvant Endocrine Treatment in a Prospective Breast Cancer Cohort
- 2012
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Ingår i: Cancer Prevention Research. - 1940-6207. ; 5:5, s. 735-745
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Tidskriftsartikel (refereegranskat)abstract
- Nonadherence to adjuvant endocrine breast cancer treatment adversely affects disease-free and overall survival. Clinical predictors of nonadherence may allow for specific interventions to reduce nonadherence and improve survival. The aim was to investigate whether clinical characteristics predict nonadherence. Clinical characteristics and information on adherence were obtained from 417 patients with breast cancer in a population-based prospective cohort from southern Sweden using patient charts, pathology reports, and questionnaires filled out at the 1- and 2-year follow-up visits. At the 1- and 2-year follow-up visits, 36 (8.6%) and 33 (9.7%) patients were nonadherent, respectively. Thirteen of the nonadherent patients declined treatment and were never prescribed endocrine treatment. A body mass index (BMI) < 25 kg/m(2), preoperative current smoking, and drinking alcohol less often than twice a month predicted nonadherence at the 1- year [relative risk (RR), 5.24; 95% confidence interval (CI), 2.75-9.97] and the 2-year visits (RR, 4.07; 95% CI, 2.11-7.84) in patients with at least two of these clinical characteristics. When low histologic grade (I) was added to the model, having at least two of these four clinical characteristics predicted nonadherence at the 1- year (RR, 4.94; 95% CI, 2.46-10.00) and the 2-year visits (RR, 4.74; 95% CI, 2.28-9.87), the two profiles had a sensitivity ranging from 60.6% to 72.7%, whereas the specificity ranged from 68.0% to 78.4%. Nonadherence at the 1- year visit was associated with an increased risk for early breast cancer events (HR, 2.97; 95% CI, 1.08-8.15), adjusted for age and tumor characteristics. In conclusion, two clinical profiles predicted early nonadherence and may allow for targeted interventions to increase adherence if validated in an independent cohort. Cancer Prev Res; 5(5); 735-45. (c) 2012 AACR.
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| 11. |
- Markkula, Andrea
(författare)
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Genetic factors, body constitution, and tumor characteristics in relation to breast cancer prognosis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prior advancements in research on biomarkers and prognostic host factors have made it increasingly clear that breast cancer is an immensely heterogeneous disease. It remains difficult to predict which patients will benefit from different breast cancer treatments. Hence, interest in personalized medicine is internationally wide-spread and growing. In paper I, we found that tumor detection mode, as well as several tumor- and preoperative patient characteristics were associated with nonadherence to adjuvant endocrine treatment. Furthermore, two clinical profiles were strongly associated with nonadherence to adjuvant endocrine breast cancer therapy at both the 1- and the 2-year follow-up visits. In paper II, we found that waist-to-hip ratio (WHR), waist circumference, as well as breast volume were associated with disease-free survival. Breast cancer patients with ER positive tumors and a breast volume ≥850 mL had a significantly shorter disease-free survival, regardless of age, WHR, waist circumference, and BMI. In paper III, a strong interaction between having any COX2 rs5277 C-allele and ER status on disease-free survival was found. The effect was further modified by breast volume. Two subgroups of patients were identified: GG carriers with a large breast volume who responded poorly to chemotherapy regardless of ER status and C-allele carriers with ER positive tumors and a large breast volume who responded poorly to endocrine treatment but responded well to chemotherapy. In paper IV, the IL6 rs1800795 Any C genotype was strongly associated with early events among patients with ER negative tumors, particularly among radiotherapy-treated patients, and among chemotherapy-treated patients regardless of ER status. In conclusion, taking a more holistic view of the patient may prove beneficial both in and outside the clinic, ultimately paving the way for more personalized breast cancer treatment.
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| 12. |
- Markkula, Andrea, et al.
(författare)
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Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort.
- 2012
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 23:8, s. 1307-1316
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients. METHODS: Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports. RESULTS: Patients with a BMI ≥ 25 kg/m(2) had larger tumors (p < 0.001) and more axillary nodal involvement (p = 0.030). Patients with a WHR > 0.85 had larger tumors (p = 0.013), more advanced histological grade (p = 0.0016), and more axillary nodal involvement (p = 0.012). Patients with right + left breast volume ≥ 850 mL were more likely to have larger tumor sizes (p = 0.018), more advanced histological grade (p = 0.031), and more axillary nodal involvement (p = 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volume ≥ 850 mL was associated with shorter disease-free survival (p = 0.004) and distant metastasis-free survival (p = 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95 % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95 %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment. CONCLUSION: A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy.
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| 13. |
- Markkula, Andrea, et al.
(författare)
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IL6 genotype, tumour ER-status, and treatment predicted disease-free survival in a prospective breast cancer cohort.
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- In breast cancer, high levels of the inflammatory cytokine interleukin-6 (IL-6) have been associated with disease-free survival and treatment resistance. Increased serum levels of IL-6 have been correlated with increased levels of NF-κβ and aromatase expression in adipose tissue. Several IL6 single nucleotide polymorphisms have been associated with breast cancer prognosis, but the impact may differ depending on tumour oestrogen receptor (ER) status. This translational study investigated the association between IL6 genotypes, ER-status, and treatment on the risk of early events among breast cancer patients.
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| 14. |
- Markkula, Andrea, et al.
(författare)
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Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 135:8, s. 1898-1910
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Tidskriftsartikel (refereegranskat)abstract
- The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(pinteraction = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment.
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| 15. |
- Markkula, Andrea, et al.
(författare)
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No association found between CYP2D6 genotype and early breast cancer events in tamoxifen-treated patients.
- 2014
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Ingår i: Acta Oncologica. - 1651-226X. ; 53:2, s. 195-200
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Tidskriftsartikel (refereegranskat)abstract
- Background. CYP2D6 is considered the key enzyme in tamoxifen metabolism. Several studies have investigated the relationship between the CYP2D6 genotype and tamoxifen treatment outcome, with discrepant results. CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy may account for some of the discrepancies. We examined the association between CYP2D6 genotype and early breast cancer events in tamoxifen-treated breast cancer patients, in relation to CYP2D6 inhibitor use, aromatase inhibitor use, and chemotherapy. Material and methods. Pre- and postoperative questionnaires on lifestyle and concomitant medications were completed by 634 primary breast cancer patients between 2002 and 2008, among whom 333 patients had ER-positive tumors and received tamoxifen. CYP2D6*3, *4, *6, *10 and *41 were genotyped. Information on clinical data, breast cancer events, and tumor characteristics was obtained from patients' charts, population registries, the Regional Tumor Registry, and pathology reports. Results. Median follow-up was 4.9 years. Neither poor metabolizers (adjusted HR 0.50; 95% CI 0.07-3.82) nor intermediate metabolizers (adjusted HR 1.00; 95% CI 0.47-2.11) had an increased risk of early breast cancer events when compared with extensive metabolizers. CYP2D6 activity score (taking into account genotype and CYP2D6 inhibitor use) was not associated with early breast cancer events (LogRank, Ptrend = 0.44). Conclusions. CYP2D6 genotype was not associated with tamoxifen treatment outcome, even when CYP2D6 inhibitor use, aromatase inhibitor use, or chemotherapy was taken into account. CYP2D6 genotype may be of minor importance for tamoxifen-treated patients in Scandinavia.
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| 16. |
- Persson, Mia, et al.
(författare)
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Impacts of smoking on endocrine treatment response in a prospective breast cancer cohort
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 115:3, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- Background:The association between smoking and breast cancer prognosis remains unclear. The purpose of this study was to investigate whether preoperative smoking was associated with prognosis in different treatment groups.Methods:This population-based cohort consisted of 1065 breast cancer patients without preoperative treatment included between 2002 and 2012 in Lund, Sweden. Smoking status was examined in relation to patient and tumour characteristics, and prognosis in different treatment groups.Results:At the preoperative visit, 21.0% smoked. Median follow-up time was 5.1 years. Overall, in the 1016 patients included in the survival analyses, there was no significant association between smoking and risk of breast cancer events (adjusted hazard ratio (adjHR): 1.45; 95% confidence interval (CI): 0.95–2.20). For the 309 aromatase inhibitor (AI)-treated patients ⩾50 years with oestrogen receptor-positive (ER+) tumours, smoking was associated with risk of breast cancer events (adjHR: 2.97; 95% CI: 1.44–6.13), distant metastasis (adjHR: 4.19; 95% CI: 1.81–9.72), and death (adjHR: 3.52; 95% CI: 1.59–7.81). Smoking was not associated with breast cancer events or distant metastasis in other treatment groups.Conclusions:Preoperative smoking was only associated with an increased risk for breast cancer events and distant metastasis in AI-treated patients. If confirmed, smoking status should be taken into consideration when selecting an endocrine therapy.British Journal of Cancer advance online publication, 9 June 2016; doi:10.1038/bjc.2016.174 www.bjcancer.com.
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| 17. |
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| 18. |
- Simonsson, Maria, et al.
(författare)
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CYP1A2 - a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients
- 2016
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Endocrine resistance is a major obstacle to optimal treatment effect in breast cancer. Some genetic markers have been proposed to predict response to aromatase inhibitors (AIs) but the data is insufficient. The aim of the study was to find new genetic treatment predictive markers of AIs.METHODS: The ongoing population-based BC-blood study in Lund, Sweden includes women with primary breast cancer. This paper is based on AI-treated patients with estrogen receptor positive tumors who underwent breast cancer surgery in 2002-2008. First, an exploratory analysis of 1931 SNPs in 227 genes involved in absorption, distribution, metabolism, and elimination of multiple medications, using DMET™ chips, was conducted in a subset of the cohort with last follow-up in December 31(st) 2011 (13 cases, 11 controls). Second, selected SNPs from the first analysis were re-analyzed concerning risk for early breast cancer events in the extended cohort of 201 AI-treated with last follow-up in June 30(th) 2014. Clinical data were obtained from medical records and population registries.RESULTS: Only CYP1A2 rs762551 C-allele was significantly associated with increased risk for early events in the 24 patients (P = 0.0007) and in the extended cohort, adjusted Hazard ratio (HR) 2.22 (95 % CI 1.03-4.80). However, the main prognostic impact was found within five years, adjusted HR 7.88 (95 % CI 2.13-29.19). The impact of the CYP1A2 rs762551 C-allele was modified by a functional polymorphism in the regulator gene AhR Arg554Lys (G > A). Compared to patients who were homozygous for the major allele in both genes (CYP1A2 A/A and AhR G/G), a 9-fold risk for early events was found in patients who had at least one minor allele in both genes, adjusted HR 8.95 (95 % CI 2.55-31.35), whereas patients with at least one minor allele in either but not both genes had a 3-fold risk for early events, adjusted HR 2.81 (95 % CI 1.07-7.33). The impact of CYP1A2 rs762551 C-allele was also modified by the CYP19A1 rs4646 C/C, adjusted HR 3.39 (95 % CI 1.60-7.16) for this combination. This association was strongest within the first five years, adjusted HR 10.42 (95 % CI 3.45-31.51).CONCLUSION: CYP1A2 rs762551 was identified as a new potential predictive marker for early breast cancer events in AI-treated breast cancer patients. Moreover, combined genotypes of CYP1A2 rs762551 and CYP19A1 rs4646 or AhR Arg554Lys could further improve prediction of early AI-treatment response. If confirmed, these results may provide a way to more personalized medicine.
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| 19. |
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| 20. |
- Simonsson, Maria, et al.
(författare)
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The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 140:1, s. 163-175
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Tidskriftsartikel (refereegranskat)abstract
- The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up, adjHR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (Pinteraction=0.048), preoperative NSAID use (Pinteraction=0.009), and tumor size (Pinteraction=0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users, adjHR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users, adjHR 4.51 (1.18-11.44) as well as in patients with large tumors, adjHR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.
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| 21. |
- Tryggvadottir, Helga, et al.
(författare)
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Interactions between ABCB1genotype and preoperative statin use impact clinical outcomes among breast cancer patients
- 2018
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 8:OCT
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Tidskriftsartikel (refereegranskat)abstract
- Multiple clinical trials investigate statins' effects in breast cancer. The ABCB1 genotype appears to influence statin response and toxicity in the cardiovascular setting. This exploratory study aimed to investigate the interplay between preoperative statin use, ABCB1 genotype, and tumor-specific expression of the statin target 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in breast cancer. Preoperative statin use, ABCB1 C3435T genotype, and HMGCR expression in relation to outcome were analyzed in 985 primary breast cancer patients from a population-based prospective cohort in Sweden from 2002 to 2012. Preoperative statin use (n = 80) was not associated with ABCB1 C3435T genotype (n = 576), HMGCR expression (n = 848), or clinical outcomes. ABCB1 C3435T TT-carriers had lower risk of breast cancer events than any C-carriers (adjusted hazard ratio (HRadj) 0.74; 95%CI 0.49, 1.12), but only in non-statin users (Pinteractio n = 0.042). Statin users with TT genotype had higher risk of distant metastasis (HRadj 4.37; 95%CI 1.20, 15.91; Pinteraction = 0.009) and shorter overall survival than other patients (HRadj 3.77; 95%CI 1.37, 10.39; Pinteractio n = 0.019). In conclusion, there were nominally significant interactions between ABCB1 genotype and preoperative statin use on clinical outcomes, while preoperative statin use was not associated with outcomes. Since this is an exploratory study of the impact of the ABCB1 genotype in relation to statin use and clinical outcomes in the breast cancer setting, the results should be interpreted with caution and warrant replication in an independent cohort, preferably in a randomized setting. Since statin use is common in breast cancer patients, it would be of interest to further elucidate the clinical impact of the ABCB1 genotype in breast cancer.
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| 22. |
- 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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