| 21. |
- Elit, L, et al.
(författare)
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Familial and hormonal risk factors for papillary serous uterine cancer
- 2002
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Ingår i: European Journal of Gynaecological Oncology. - 0392-2936. ; 23:3, s. 187-190
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To identify genetic and non-genetic risk factors for papillary serous uterine cancer. Methods: A case-control study was conducted. Case women with papillary serous uterine cancer were compared with two control groups: 1) women with endometrioid uterine cancer and 2) healthy women with no past history of cancer. Cases and controls were matched for age (within two years) and ethnic group. All study subjects completed a questionnaire addressing family history. The cases and healthy controls were assessed for factors associated with estrogen exposure. Results: The risks of breast cancer (RR 1.84, Cl 1.03-331) and of prostate cancer (RR 2.21, CI 0.77-6.37) were higher among the relatives of patients with papillary serous uterine cancer, than among relatives of those with endometrioid uterine cancer. Other significant risk factors included weight at 18 years (p = 0.04) and the use of estrogen replacement therapy (p = 0.04). Conclusion: Relatives of women with papillary serous cancer of the uterus had an increased risk of breast and prostate cancer. Hormonal exposure also increases the risk for this cancer. These Findings suggest that predisposing genetic factors, possibly related to hormone metabolism, may be common to the three forms of cancer.
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| 22. |
- Ellberg, Carolina, et al.
(författare)
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Breast cancer and spider telangiectasias at diagnosis and its relation to histopathology and prognosis: a population-based study.
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 131:1, s. 177-186
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is one of the hallmarks of breast cancer. The status of angiogenesis is important in therapy choice. Spider telangiectasias (telangiectasias) may reflect an increased ability to form vessels. Our first aim was to identify patient and tumor characteristics associated with the occurrence of telangiectasias at the time of breast cancer diagnosis. The second aim was to study the overall survival in relation to the occurrence of telangiectasias at the time of breast cancer diagnosis. A standardized questionnaire was used to interview 1682 consecutive breast cancer patients about risk factors between 1980 and 2009. Occurrence of telangiectasias at the time of breast cancer diagnosis on the upper thorax, head, and/or neck was recorded by one physician. In the cohort, 93 women (5.5%) had telangiectasias. Occurrence of telangiectasias was positively associated with weight, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.00-1.05) per kg, ever-use of oral contraceptives OR 2.67(CI 1.55-4.63) and hormone replacement therapy OR 2.68(CI 1.63-4.39), and negatively associated with parity OR 0.45(CI 0.25-0.79). Telangiectasias were not present in patients with comedo breast cancer. Patients with occurrences of telangiectasias diagnosed before the age of 50 had a statistically non-significant worse overall survival, whereas the patients with occurrences of telangiectasias diagnosed at age 50 or after had a statistically significant better overall survival (P interaction = 0.016). The relationship between the occurrence of telangiectasias and the overall survival in the older patient-group was independent of ever-use of HRT. Hormonal risk factors for breast cancer were associated with the occurrence of spider telangiectasias. The occurrence of telangiectasias may reflect the angiogenic status of the tumor. We hypothesize that telangiectasias could be used as selection criteria for anti-angiogenic therapy in younger breast cancer patients. Therefore, patients with comedo breast cancers maybe a group that may benefit less from anti-angiogenic therapy.
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| 23. |
- Ellberg, Carolina, et al.
(författare)
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Current smoking is associated with a larger waist circumference and a more androgenic profile in young healthy women from high-risk breast cancer families
- 2018
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 29:2, s. 243-251
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to elucidate the interplay between current smoking, anthropometric measurements, and endogenous hormone levels in women ≤ 40 years. Questionnaires on lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body measurements were obtained 5–10 days before predicted onset of the next menstrual period. Women without smoking status, who were currently breastfeeding, or using hormonal contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR) (adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp = 0.0002). While in current OC users estradiol levels were higher in smokers compared with non-smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with both current smoking (adjp ≤ 0.016) and higher levels of androstenedione (adjp = 0.05) or bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was observed in current smokers compared with non-smokers, but not in current OC users. Irrespective of OC use, current smoking was associated with increased waist circumference.
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| 24. |
- Ellberg, Carolina, et al.
(författare)
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Impact of a paternal origin of germline BRCA1/2 mutations on the age at breast and ovarian cancer diagnosis in a Southern Swedish cohort.
- 2015
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 54:1, s. 39-50
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Tidskriftsartikel (refereegranskat)abstract
- Three studies have reported that BRCA1/2 mutations of paternal origin confer an earlier age at breast cancer diagnosis compared with maternal origin. The primary aim of this study was to investigate the impact of parental origin of BRCA1/2 mutations on age at breast and ovarian cancer diagnosis. This study included 577 female BRCA1/2 mutation carriers. All BRCA1/2 mutation carriers belonged to families registered between 1993 and 2011 at the Oncogenetic Clinic at Skånes University Hospital, Lund, Sweden. Cox proportional hazard ratios were used to analyze time to breast or ovarian cancer diagnosis. A novel finding was that carriers of BRCA1 mutations of paternal origin were 4 years older at age of ovarian cancer (P = 0.009) compared with those carrying a BRCA1 mutation of maternal origin. BRCA1 carriers with mutations of paternal origin were 4 years younger at breast cancer diagnosis (P = 0.017) compared with those carrying a BRCA1 mutation of maternal origin, which is in agreement with three previous studies. Both findings were adjusted for of year of inclusion, birth date, and oral contraceptive pill use. No associations between parental origin of BRCA2 mutations and time to breast or ovarian cancer diagnosis were found. An attempt to handle a potential selection bias regarding use of oral contraceptives was made using multiple imputations by chained equations. The observed age difference may allow a greater understanding of mechanisms associated with the differences in cancer penetrance in BRCA1/2 mutation carriers, some of which may depend on paternal origin. © 2014 Wiley Periodicals, Inc.
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| 25. |
- Godina, Christopher, et al.
(författare)
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Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.
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| 26. |
- Godina, Christopher, et al.
(författare)
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Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer
- 2023
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 199:2, s. 335-347
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Tidskriftsartikel (refereegranskat)abstract
- PurposeCaveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer.MethodsA cohort of 1017 breast cancer patients (inclusion 2002–2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments).ResultsOnly one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86–9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24–4.04). No other genotypes or haplotypes were associated with clinical outcome.ConclusionCAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.
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| 27. |
- Godina, Christopher, et al.
(författare)
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High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome
- 2024
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.METHODS: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells.RESULTS: In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression.CONCLUSION: CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.
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| 28. |
- Godina, Christopher, et al.
(författare)
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Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer
- 2022
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.Methods: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002-2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression. Investigations into CAV1 functional pathways was conducted in the STRING, GOBO, and TCGA databases.Results: CAV1 expression was associated with non-luminal subtypes, cell cycle control, inflammation, epithelialmesenchymal transition, and the IGF/Insulin system. Generally, CAV1 was not associated with recurrence risk. Stromal CAV1's impact on recurrence risk was modified by BMI > 25 kg/m(2) (P-interaction = 0.002), waist > 80 cm (P-interaction = 0.005), and invasive tumor size (pT2/3/4) (P-interaction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRs(adj) > 1.61). In all patients, positive cytoplasmic CAV1 conferred > 2-fold risk for contralateral disease HRadj 2.63 (95% CI 1.36-5.10). Strong stromal CAV1 conferred nearly 2-fold risk for locoregional recurrence HRadj 1.88 (95% CI 1.09-3.24).Conclusions: CAV1's prognostic impact depended on its localization, anthropometric, and tumor factors. Stromal CAV1 predicted high recurrence risk in a group of supposedly "low-risk' patients. Cytoplasmic CAV1 predicted metachronous contralateral disease. If confirmed, CAV1 could be used as treatment target and for risk stratification.
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| 29. |
- Godina, Christopher, et al.
(författare)
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Prognostic Impact of Menopausal Hormone Therapy in Breast Cancer Differs According to Tumor Characteristics and Treatment
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated how a history of menopausal hormone therapy (MHT) impacts clinical outcomes overall and in different subgroups of breast cancer patients. The study included 814 primary breast cancer patients aged ≥50 years in Sweden (2002–2012) with follow-up until 2016. Associations between patient- and tumor characteristics, recurrences, and overall survival were analyzed in relation to MHT. After a median follow-up of 7 years, 119 recurrences, and 111 deaths occurred. Ever MHT (n = 433, 53.2%) was associated with a lower BMI, frequency of alcohol abstinence, and histological grade, higher frequency of oral contraceptive use, and lobular cancer. Overall, MHT was not associated with prognosis, but there were significant effect modifications by estrogen receptor (ER) status, node status, main histological type, and aromatase inhibitor (AI) treatment on recurrence-risk (all Pinteractions≤ 0.017). MHT conferred an increased recurrence-risk in patients with ER- tumors, adjusted Hazard Ratio (HRadj) 3.99 (95% Confidence Interval (CI) 1.40–11.33), in node-negative patients HRadj 1.88 (95% CI 1.11–3.17), and in non-AI-treated patients HRadj 1.81 (95% CI 1.01–3.24), but decreased recurrence-risk in AI-treated patients HRadj 0.46 (95% CI 0.25–0.84) and in patients with lobular cancer HRadj 0.15 (95% CI 0.04–0.64). MHT was associated with lower risk of death in node-positive patients HRadj of 0.48 (95% CI 0.27–0.86) and in AI-treated patients HRadj of 0.41 (95% CI 0.22–0.77), but not in other patients (both Pinteractions≤ 0.027). A history of MHT may have prognostic value for certain subgroups of breast cancer patients such as AI-treated or node-negative patients.
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| 30. |
- Godina, Christopher, et al.
(författare)
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Prognostic impact of tumor-specific insulin-like growth factor binding protein 7 (IGFBP7) levels in breast cancer : A prospective cohort study
- 2021
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 42:11, s. 1314-1325
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic impact of insulin-like growth factor binding protein 7 (IGFBP7) in breast cancer is unclear. Host factors, including lifestyle, anthropometry and metabolic profile, might influence tumor-specific IGFBP7. This study aimed to investigate whether IGFBP7 levels and messenger ribonucleic acid (mRNA) expression are associated with the patient and tumor characteristics and prognosis in breast cancer. Patients with primary breast cancer in Lund, Sweden, were included preoperatively in the study between 2002 and 2012 (n = 1018). Tumor-specific IGFBP7 protein levels were evaluated with immunohistochemistry using tissue microarrays in tumors from 878 patients. IGFBP7 mRNA expression and its corresponding clinical data were obtained from The Cancer Genome Atlas and analyzed for 809 patients. Tumor-specific IGFBP7 protein levels were categorized based on Histo 300 scores into IGFBP7low (6.2%), IGFBP7intermediate (75.7%) and IGFBP7high (18.1%). Both low IGFBP7 protein levels and mRNA expression were associated with less aggressive tumor characteristics. Overall, IGFBP7low conferred low recurrence risk. The prognostic impact of IGFBP7high varied according to any alcohol consumption and tamoxifen treatment. IGFBP7high was associated with low recurrence risk in alcohol consumers but high recurrence risk in alcohol abstainers (Pinteraction= 0.039). Moreover, the combination of IGFBP7high and estrogen receptor-positive tumors was associated with low recurrence risk only in tamoxifen-treated patients (Pinteraction= 0.029). To conclude, IGFBP7low might be a good, independent prognosticator in breast cancer. The prognostic impact of IGFBP7high depends on host factors and treatment. IGFBP7 merits further investigation to confirm whether it could be a suitable biomarker for treatment selection.
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