| 11. |
- Gabrielson, Marike, et al.
(författare)
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Inclusion of Endogenous Plasma Dehydroepiandrosterone Sulfate and Mammographic Density in Risk Prediction Models for Breast Cancer
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 29:3, s. 574-581
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Tidskriftsartikel (refereegranskat)abstract
- Background: Endogenous hormones and mammographic density are risk factors for breast cancer. Joint analyses of the two may improve the ability to identify high-risk women.Methods: This study within the KARMA cohort included pre-diagnostic measures of plasma hormone levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and mammographic density in 629 cases and 1,223 controls, not using menopausal hormones. We evaluated the area under the receiver-operating curve (AUC) for risk of breast cancer by adding DHEA, DHEAS, and mammographic density to the Gail or Tyrer-Cuzick 5-year risk scores or the CAD2Y 2-year risk score.Results: DHEAS and percentage density were independently and positively associated with breast cancer risk (P = 0.007 and P < 0.001, respectively) for postmenopausal, but not premenopausal, women. No significant association was seen for DHEA. In postmenopausal women, those in the highest tertiles of both DHEAS and density were at greatest risk of breast cancer (OR, 3.5; 95% confidence interval, 1.9-6.3) compared with the lowest tertiles. Adding DHEAS significantly improved the AUC for the Gail (+2.1 units, P = 0.008) and Tyrer-Cuzick (+1.3 units, P = 0.007) risk models. Adding DHEAS to the Gail and Tyrer-Cuzick models already including mammographic density further increased the AUC by 1.2 units (P = 0.006) and 0.4 units (P = 0.007), respectively, compared with only including density.Conclusions: DHEAS and mammographic density are independent risk factors for breast cancer and improve risk discrimination for postmenopausal breast cancer.Impact: Combining DHEAS and mammographic density could help identify women at high risk who may benefit from individualized breast cancer screening and/or preventive measures among postmenopausal women.
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| 12. |
- Hammarström, Mattias, et al.
(författare)
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Side effects of low-dose tamoxifen : results from a six-armed randomised controlled trial in healthy women
- 2023
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Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 129:1, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women. Methods: In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status. Results: Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women. Conclusions: Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings. Trial registration: ClinicalTrials.gov ID: NCT03346200.
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| 13. |
- He, Wei, et al.
(författare)
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Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer
- 2023
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy. OBJECTIVE To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022. EXPOSURE Discontinuation of adjuvant hormone therapy. MAIN OUTCOMES AND MEASURES The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy. RESULTS A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results. CONCLUSIONS AND RELEVANCE In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.
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| 14. |
- He, Wei, et al.
(författare)
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Pregnancy outcomes in women with a prior cervical intraepithelial neoplasia grade 3 diagnosis : a nationwide population-based cohort study with sibling comparison design
- 2022
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Ingår i: Annals of Internal Medicine. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0003-4819. ; 175:2, s. 210-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes. Objective: To investigate pregnancy outcomes in women diagnosed with CIN3. Design: Population- and sibling-matched cohort study. Setting: Sweden, 1973-2018. Participants: General population comparison included 78 450 singletons born to women diagnosed with CIN3 and 784 500 matched singletons born to women in the general population who had no CIN3 diagnosis; sibling comparison included 23 199 singletons born to women diagnosed with CIN3 and 28 135 singletons born to their sisters without a CIN3 diagnosis. Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; Infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth. Results: Compared with the matched general population, women previously diagnosed with CIN3 were more likely to have a preterm birth especially extremely preterm (22-28 weeks; OR, 3.00; 95% CI, 2.69-3.34) and spontaneous preterm (OR, 2.12; 95% CI, 2.05-2.20) birth, infection-related outcomes including chorioamnionitis (OR, 3.23; 95% CI, 2.89-3.62) and infant sepsis (OR, 1.72; 95% CI, 1.60-1.86), and early neonatal death (OR, 1.83; 95% CI, 1.61-2.09). Sibling comparison analyses rendered largely similar results. Over time the risk difference attenuated for all outcomes and disappeared for early neonatal death. Limitations: Lack of data on CIN3 treatment and spontaneous abortion. Conclusion: Prior history of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN3 may be minimized by improving treatment modalities.
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| 15. |
- Holowko, Natalie, et al.
(författare)
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Heritability of mammographic breast density, density change, microcalcifications, and masses
- 2020
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Ingår i: Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-5472. ; 80:7, s. 1590-1600
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important since the mechanisms through which they are associated with breast cancer are not well known. Methods: Mammographic screening history and detailed questionnaire data for 56,820 women from the KARMA prospective cohort study were used. The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC – cm2/year) were estimated using 1,940 sister pairs. We investigated the association between a genetic predisposition to breast cancer and mammographic features, among women with family history of breast cancer information (N=49,674) and a polygenic risk score (PRS, N=9,365). Results: Heritability was estimated at 58% (95% CI: 48%, 67%) for MD, 23% (2%, 45%) for microcalcifications, and 13% (1%, 25%) for masses. The estimated heritability for MDC was essentially null (2%, 95% CI: -8%, 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction. Conclusions: We confirmed previous findings of heritability in MD, and also found heritability of the number of microcalcifications and masses at baseline. Since these features are associated with breast cancer risk, and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer.
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| 16. |
- Hu, Kejia, et al.
(författare)
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Neuroendocrine pathways and breast cancer progression : a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts
- 2022
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue.METHODS: We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively.RESULTS: In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA.CONCLUSION: Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.
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| 17. |
- Jung, Audrey Y, et al.
(författare)
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Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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| 18. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 19. |
- Klintman, Marie, et al.
(författare)
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Postmenopausal overweight and breast cancer risk; results from the KARMA cohort
- 2022
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 196:1, s. 185-196
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To study the risk of incident breast cancer and subtype-specific breast cancer in relation to excess body weight in a contemporary Swedish prospective cohort study, The Karolinska Mammography Project for Risk Prediction of Breast Cancer, KARMA. Methods: A total of 35,412 postmenopausal women attending mammography and included in the KARMA study provided baseline data on body mass index (BMI) and potential confounders. During eight years of follow-up, 822 incident invasive breast cancer cases were identified. Results: Women with overweight (BMI ≥ 25–< 30 kg/m2) constituting 34% of the study cohort had an increased risk of incident breast cancer with an adjusted Hazard Ratio (HRadj) 1.19 (95% CI 1.01–1.4). A similar, however, non-significant, association was found for women with obesity (BMI ≥ 30 kg/m2) conferring 13% of the cohort, with a HRadj of 1.19 (95% CI 0.94–1.5). Overweight was associated with risk of node-negative disease (HRadj 1.29, 95% CI 1.06–1.58), whereas obesity was associated with node-positive disease (HRadj 1.64, 95% CI 1.09–2.48). Both overweight and obesity were associated with risk of estrogen receptor positive (ER+) disease (HRadj 1.20, 95% CI 1.00–1.44 and HRadj 1.33, 95% CI 1.03–1.71, respectively), and low-grade tumors (HRadj 1.25, 95% CI 1.02–1.54, and HRadj 1.40, 95% CI 1.05–1.86, respectively). Finally, obesity was associated with ER+HER2 negative disease (HRadj 1.37, 95% CI 1.05–1.78) and similarly luminal A tumors (HRadj 1.43, 95% CI 1.02–2.01). Conclusion: Overweight and obesity are associated with an increased risk of developing breast cancer, specifically ER+, low-grade, and for obesity, node-positive, high-risk breast cancer indicating a further need for risk communication and preventive programs.
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| 20. |
- Lu, Donghao, et al.
(författare)
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A shared genetic contribution to breast cancer and schizophrenia.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09-0.19) and identify a shared locus at 19p13 (GATAD2A) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.
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