| 1. |
- Ahearn, Thomas U., et al.
(author)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Journal article (peer-reviewed)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 2. |
- Aine, Mattias, et al.
(author)
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Molecular analyses of triple-negative breast cancer in the young and elderly
- 2021
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In: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 23:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Breast cancer in young adults has been implicated with a worse outcome. Analyses of genomic traits associated with age have been heterogenous, likely because of an incomplete accounting for underlying molecular subtypes. We aimed to resolve whether triple-negative breast cancer (TNBC) in younger versus older patients represent similar or different molecular diseases in the context of genetic and transcriptional subtypes and immune cell infiltration.PATIENTS AND METHODS: In total, 237 patients from a reported population-based south Swedish TNBC cohort profiled by RNA sequencing and whole-genome sequencing (WGS) were included. Patients were binned in 10-year intervals. Complimentary PD-L1 and CD20 immunohistochemistry and estimation of tumor-infiltrating lymphocytes (TILs) were performed. Cases were analyzed for differences in patient outcome, genomic, transcriptional, and immune landscape features versus age at diagnosis. Additionally, 560 public WGS breast cancer profiles were used for validation.RESULTS: Median age at diagnosis was 62 years (range 26-91). Age was not associated with invasive disease-free survival or overall survival after adjuvant chemotherapy. Among the BRCA1-deficient cases (82/237), 90% were diagnosed before the age of 70 and were predominantly of the basal-like subtype. In the full TNBC cohort, reported associations of patient age with changes in Ki67 expression, PIK3CA mutations, and a luminal androgen receptor subtype were confirmed. Within DNA repair deficiency or gene expression defined molecular subgroups, age-related alterations in, e.g., overall gene expression, immune cell marker gene expression, genetic mutational and rearrangement signatures, amount of copy number alterations, and tumor mutational burden did, however, not appear distinct. Similar non-significant associations for genetic alterations with age were obtained for other breast cancer subgroups in public WGS data. Consistent with age-related immunosenescence, TIL counts decreased linearly with patient age across different genetic TNBC subtypes.CONCLUSIONS: Age-related alterations in TNBC, as well as breast cancer in general, need to be viewed in the context of underlying genomic phenotypes. Based on this notion, age at diagnosis alone does not appear to provide an additional layer of biological complexity above that of proposed genetic and transcriptional phenotypes of TNBC. Consequently, treatment decisions should be less influenced by age and more driven by tumor biology.
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| 3. |
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| 4. |
- Andersson, Ingvar
(author)
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Breast tomosynthesis in practice
- 2008
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 10:Suppl. 3
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Conference paper (peer-reviewed)
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| 5. |
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| 6. |
- Arason, Adalgeir, et al.
(author)
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Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families
- 2010
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 12:4, s. R50-
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Journal article (peer-reviewed)abstract
- Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.
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| 7. |
- Bergqvist, Malin, et al.
(author)
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Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
- 2020
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 22:1
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Journal article (peer-reviewed)abstract
- Background: Obesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses. Methods: Among 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression. Results: Study participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HRadj = 0.52, 95% CI 0.31-0.88) and OS (HRadj = 0.64, 95% CI 0.44-0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease. Conclusions: Low CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making.
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| 8. |
- Bhoo-Pathy, Nirmala, et al.
(author)
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Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
- 2015
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 17
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Journal article (peer-reviewed)abstract
- Introduction: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. Methods: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. Results: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR = 0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; P-trend = 0.029. While there was no significant effect modification by hormone receptor status (P = 0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P = 0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR = 0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (P-trend = 0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR = 0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. Conclusions: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.
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| 9. |
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| 10. |
- Borgquist, Signe, et al.
(author)
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Diet and body constitution in relation to sub-groups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators.
- 2007
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In: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 9:1, s. 11-11
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Journal article (peer-reviewed)abstract
- Background The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. Method A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmo Diet and Cancer study ( Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. Results A large hip circumference and high body mass index were associated with high grade tumours ( P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation ( P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation ( P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D-1 overexpression ( P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. Conclusion Low energy and low total fat ( polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D1 and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results.
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