scholarly journals Circulating proteins reveal prior use of menopausal hormonal therapy and increased risk of breast cancer

2021 ◽  
Author(s):  
Cecilia E Thomas ◽  
Leo Dahl ◽  
Sanna Byström ◽  
Yan Chen ◽  
Mathias Uhlén ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Prediction ◽  
Hormonal Therapy ◽  
Prediction Models ◽  
Breast Cancer Diagnosis ◽  
Case Control ◽  
Data Driven ◽  
Association Analyses ◽  
Increased Risk ◽  
Data Driven Approach

Background: Risk prediction is crucial for early detection and prognosis of breast cancer. Circulating plasma proteins could provide a valuable source to increase the validity of risk prediction models, however, no such markers have yet been identified for clinical use. Methods: EDTA plasma samples from 183 breast cancer cases and 366 age-matched controls were collected prior to diagnosis from the Swedish breast cancer cohort KARMA. The samples were profiled on 700 circulating proteins using an exploratory affinity proteomics approach. Linear association analyses were performed on case-control status and a data-driven analysis strategy was applied to cluster the women on their plasma proteome profiles in an unsupervised manner. The resulting clusters were subsequently annotated for the differences in phenotypic characteristics, clinical parameters, and genetic risk. Results: Using the data-driven approach we identified five clusters with distinct proteomic plasma profiles. Women in a particular sub-group (cluster 1) were significantly more likely to have used menopausal hormonal therapy (MHT), more likely to get a breast cancer diagnosis, and were older compared to the remaining clusters. The levels of circulating proteins in cluster 1 were decreased for proteins related to DNA repair and cell replication and increased for proteins related to mammographic density and female tissues. In contrast, classical dichotomous case-control analyses did not reveal any proteins significantly associated with future breast cancer. Conclusion: Using a data-driven approach, we identified a subset of women with circulating proteins associated with previous use of MHT and risk of breast cancer. Our findings point to the potential long-lasting effects of MHT on the circulating proteome even after ending the treatment, and hence provide valuable insights concerning risk predication of breast cancer.

scholarly journals Rare Germline Pathogenic Variants Identified by Multigene Panel Testing and the Risk of Aggressive Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1495
Author(s):  
Tú Nguyen-Dumont ◽  
James G. Dowty ◽  
Robert J. MacInnis ◽  
Jason A. Steen ◽  
Moeen Riaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Prediction ◽  
Prediction Models ◽  
Risk Prediction Models ◽  
Aggressive Prostate Cancer ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Predisposition Genes ◽  
Rare Genetic Variants

While gene panel sequencing is becoming widely used for cancer risk prediction, its clinical utility with respect to predicting aggressive prostate cancer (PrCa) is limited by our current understanding of the genetic risk factors associated with predisposition to this potentially lethal disease phenotype. This study included 837 men diagnosed with aggressive PrCa and 7261 controls (unaffected men and men who did not meet criteria for aggressive PrCa). Rare germline pathogenic variants (including likely pathogenic variants) were identified by targeted sequencing of 26 known or putative cancer predisposition genes. We found that 85 (10%) men with aggressive PrCa and 265 (4%) controls carried a pathogenic variant (p < 0.0001). Aggressive PrCa odds ratios (ORs) were estimated using unconditional logistic regression. Increased risk of aggressive PrCa (OR (95% confidence interval)) was identified for pathogenic variants in BRCA2 (5.8 (2.7–12.4)), BRCA1 (5.5 (1.8–16.6)), and ATM (3.8 (1.6–9.1)). Our study provides further evidence that rare germline pathogenic variants in these genes are associated with increased risk of this aggressive, clinically relevant subset of PrCa. These rare genetic variants could be incorporated into risk prediction models to improve their precision to identify men at highest risk of aggressive prostate cancer and be used to identify men with newly diagnosed prostate cancer who require urgent treatment.

scholarly journals Genomic Risk Prediction for Breast Cancer in Older Women

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3533
Author(s):  
Paul Lacaze ◽  
Andrew Bakshi ◽  
Moeen Riaz ◽  
Suzanne G. Orchard ◽  
Jane Tiller ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Risk Prediction ◽  
Prediction Models ◽  
Cox Regression ◽  
Susceptibility Genes ◽  
Controlled Clinical Trial ◽  
Polygenic Risk Score ◽  
Double Blind ◽  
Genomic Risk

Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40–69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3–1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2–1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2–3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56–0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59–0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.

scholarly journals Population-Based Estimates of the Age-Specific Cumulative Risk of Breast Cancer for Pathogenic Variants in CHEK2: Findings from the Australian Breast Cancer Family Registry

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1378
Author(s):  
Tú Nguyen-Dumont ◽  
James G. Dowty ◽  
Jason A. Steen ◽  
Anne-Laure Renault ◽  
Fleur Hammet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Risk ◽  
Population Based ◽  
Case Control ◽  
Cancer Information ◽  
Case Control Studies ◽  
Breast Cancer Family ◽  
Pathogenic Variants ◽  
Increased Risk ◽  
Control Family

Case-control studies of breast cancer have consistently shown that pathogenic variants in CHEK2 are associated with about a 3-fold increased risk of breast cancer. Information about the recurrent protein-truncating variant CHEK2 c.1100delC dominates this estimate. There have been no formal estimates of age-specific cumulative risk of breast cancer for all CHEK2 pathogenic (including likely pathogenic) variants combined. We conducted a population-based case-control-family study of pathogenic CHEK2 variants (26 families, 1071 relatives) and estimated the age-specific cumulative risk of breast cancer using segregation analysis. The estimated hazard ratio for carriers of pathogenic CHEK2 variants (combined) was 4.9 (95% CI 2.5–9.5) relative to non-carriers. The HR for carriers of the CHEK2 c.1100delC variant was estimated to be 3.5 (95% CI 1.02–11.6) and the HR for carriers of all other CHEK2 variants combined was estimated to be 5.7 (95% CI 2.5–12.9). The age-specific cumulative risk of breast cancer was estimated to be 18% (95% CI 11–30%) and 33% (95% CI 21–48%) to age 60 and 80 years, respectively. These findings provide important information for the clinical management of breast cancer risk for women carrying pathogenic variants in CHEK2.

Receipt of Screening Mammography by Insured Women Diagnosed With Breast Cancer and Impact on Outcomes

2021 ◽  
Author(s):  
Marissa B. Lawson ◽  
Christoph I. Lee ◽  
Daniel S. Hippe ◽  
Shasank Chennupati ◽  
Catherine R. Fedorenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Late Stage ◽  
Breast Cancer Diagnosis ◽  
Screening Mammography ◽  
Socioeconomic Deprivation ◽  
Tumor Characteristics ◽  
Stage Disease ◽  
Increased Risk ◽  
Late Stage Disease

Background: The purpose of this study was to determine factors associated with receipt of screening mammography by insured women before breast cancer diagnosis, and subsequent outcomes. Patients and Methods: Using claims data from commercial and federal payers linked to a regional SEER registry, we identified women diagnosed with breast cancer from 2007 to 2017 and determined receipt of screening mammography within 1 year before diagnosis. We obtained patient and tumor characteristics from the SEER registry and assigned each woman a socioeconomic deprivation score based on residential address. Multivariable logistic regression models were used to evaluate associations of patient and tumor characteristics with late-stage disease and nonreceipt of mammography. We used multivariable Cox proportional hazards models to identify predictors of subsequent mortality. Results: Among 7,047 women, 69% (n=4,853) received screening mammography before breast cancer diagnosis. Compared with women who received mammography, those with no mammography had a higher proportion of late-stage disease (34% vs 10%) and higher 5-year mortality (18% vs 6%). In multivariable modeling, late-stage disease was most associated with nonreceipt of mammography (odds ratio [OR], 4.35; 95% CI, 3.80–4.98). The Cox model indicated that nonreceipt of mammography predicted increased risk of mortality (hazard ratio [HR], 2.00; 95% CI, 1.64–2.43), independent of late-stage disease at diagnosis (HR, 5.00; 95% CI, 4.10–6.10), Charlson comorbidity index score ≥1 (HR, 2.75; 95% CI, 2.26–3.34), and negative estrogen receptor/progesterone receptor status (HR, 2.09; 95% CI, 1.67–2.61). Nonreceipt of mammography was associated with younger age (40–49 vs 50–59 years; OR, 1.69; 95% CI, 1.45–1.96) and increased socioeconomic deprivation (OR, 1.05 per decile increase; 95% CI, 1.03–1.07). Conclusions: In a cohort of insured women diagnosed with breast cancer, nonreceipt of screening mammography was significantly associated with late-stage disease and mortality, suggesting that interventions to further increase uptake of screening mammography may improve breast cancer outcomes.

Tamoxifen use correlates with increased risk of hip fractures in older women with breast cancer: A case-control study in Taiwan

2018 ◽  
Vol 19 (1) ◽  
pp. 56-60 ◽  
Author(s):  
Shih-Chang Hung ◽  
Kuan-Fu Liao ◽  
Hung-Chang Hung ◽  
Cheng-Li Lin ◽  
Po-Chang Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Hip Fractures ◽  
Case Control Study ◽  
Case Control ◽  
Increased Risk ◽  
Control Study

scholarly journals Oral Contraceptive Use and Breast Cancer Risk Assessment: A Systematic Review and Meta-Analysis of Case-Control Studies, 2009–2020

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5654
Author(s):  
Agnieszka Barańska ◽  
Agata Błaszczuk ◽  
Wiesław Kanadys ◽  
Maria Malm ◽  
Katarzyna Drop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptive ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Case Control ◽  
Cochrane Library ◽  
Control Group ◽  
Case Control Studies ◽  
Increased Risk ◽  
Breast Cancer Risk Assessment

To perform a meta-analysis of case-control studies that addressed the association between oral contraceptive pills (OC) use and breast cancer (BrCa), PubMED (MEDLINE), Embase, and the Cochrane Library were searched to identify case-control studies of OC and BrCa published between 2009 and 2020. We used the DerSimonian–Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs), and the Mantel–Haenszel test to assess the association between OC use and cancer. Forty-two studies were identified that met the inclusion criteria and we included a total of 110,580 women (30,778 into the BrCa group and 79,802 into the control group, of which 15,722 and 38,334 were using OC, respectively). The conducted meta-analysis showed that the use of OC was associated with a significantly increased risk of BrCa in general, OR = 1.15, 95% CI: 1.01 to 1.31, p = 0.0358. Regarding other risk factors for BrCa, we found that increased risk was associated significantly with early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa. Despite our conclusion that birth control pills increase the cancer risk being supported by extensive previous studies and meta-analyzes, further confirmation is required.

scholarly journals Association of a Novel KIF26B Gene Polymorphism with Susceptibility to Schizophrenia and Breast Cancer: A Case-Control Study

2021 ◽  
Author(s):  
Saman SARGAZI ◽  
Milad HEIDARI NIA ◽  
Shekoufeh MIRINEJAD ◽  
Mahdiyeh MOUDI ◽  
Mahdiyeh JAFARI SHAHROUDI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
De Novo ◽  
Case Control ◽  
Amplification Refractory Mutation System ◽  
Salting Out ◽  
Current Case ◽  
Increased Risk ◽  
Mutation System ◽  
Control Study

Background: KIF26B gene is found to play essential roles in regulating different aspects of cell proliferation and development of the nervous system. We aimed to determine if rs12407427 T/C polymorphism could affect susceptibility to schizophrenia (SZN) and breast cancer (BC), the two genetically correlated diseases. Methods: The current case-control study was performed from Aug 2018 to Dec 2018. Briefly, 159 female pathologically confirmed BC cases referring to Alzahra Hospital, Isfahan, Iran, and 102 psychologically confirmed SZN patients (60 males and 42 females) admitted to Baharan Hospital, Zahedan, Iran, were enrolled. Using the salting-out method, genomic DNA was extracted, and variants were genotyped using allele-specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method. Results: The results revealed a significant association between the KIF26B rs12407427 codominant CT (P=0.001), CC (P=0.0001), dominant CT+CC, and recessive CC (P=0.001) genotypes with the risk of developing SZN. Significant correlations were also found regarding rs12407427 and BC susceptibility in different inheritance models, including over-dominant CT (P=0.026), dominant CT+CC (P=0.001), recessive CC (P=0.009), and codominant CT and CC (P=0.001) genotypes. The over-presence of the C allele was also correlated with an increased risk for SZN (P=0.0001) and BC (P=0.0001). Finally, computational analysis predicted that T/C variation in this polymorphism could change the binding sites in proteins involved in splicing. Conclusion: rs12407427 T/C as a de novo KIF26B variant might be a novel genetic biomarker for SZN and/or BC susceptibility in a sample of the Iranian population.

Postscript: starting oral contraceptives (25 May, page 41)

1992 ◽  
Vol 30 (14) ◽  
pp. 56.1-56
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptives ◽  
Contraceptive Use ◽  
Causal Relation ◽  
Case Control ◽  
Term Pregnancy ◽  
Oral Contraceptive Use ◽  
Increased Risk ◽  
The Uk

In our article on oral contraceptives (OCs) we state that ‘oral contraceptives increase the risk of breast cancer with long-term use but reduce the risk of endometrial and ovarian cancer’. Some commentators have questioned the breast cancer risk. The UK National Case-Control (UKNCC) study, which looked at oral contraceptive use in women with breast cancer diagnosed before age 36, found a trend for increased risk associated with duration of use.1 ‘The simplest and most plausible explanation’, say the authors of the study, ‘must be that there is a substantial causal relation between prolonged use and breast cancer in young women.’ The increased risk seems to be associated particularly with OC use before the first full-term pregnancy.2 Several studies found no excess risk in OC users aged 45 or over, few of whom had taken the pill before their first pregnancy.3–5 In the UKNCC study the relative risk of breast cancer was 1.43 after 4–8 years’ use and 1.74 after more than 8 years’ use. In broad terms this means that three women in 1000 who use oral contraceptives for 4 or more years might be expected to be under treatment for breast cancer by age 36, compared with two per 1000 non-users.

A Validated Risk Prediction Model for Breast Cancer in US Black Women

2021 ◽  
Author(s):  
Julie R. Palmer ◽  
Gary Zirpoli ◽  
Kimberly A. Bertrand ◽  
Tracy Battaglia ◽  
Leslie Bernstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Black Women ◽  
Prediction Model ◽  
Risk Prediction ◽  
Prediction Models ◽  
Risk Prediction Model ◽  
Risk Prediction Models ◽  
Relative Risks ◽  
Discriminatory Accuracy

PURPOSE Breast cancer risk prediction models are used to identify high-risk women for early detection, targeted interventions, and enrollment into prevention trials. We sought to develop and evaluate a risk prediction model for breast cancer in US Black women, suitable for use in primary care settings. METHODS Breast cancer relative risks and attributable risks were estimated using data from Black women in three US population-based case-control studies (3,468 breast cancer cases; 3,578 controls age 30-69 years) and combined with SEER age- and race-specific incidence rates, with incorporation of competing mortality, to develop an absolute risk model. The model was validated in prospective data among 51,798 participants of the Black Women's Health Study, including 1,515 who developed invasive breast cancer. A second risk prediction model was developed on the basis of estrogen receptor (ER)–specific relative risks and attributable risks. Model performance was assessed by calibration (expected/observed cases) and discriminatory accuracy (C-statistic). RESULTS The expected/observed ratio was 1.01 (95% CI, 0.95 to 1.07). Age-adjusted C-statistics were 0.58 (95% CI, 0.56 to 0.59) overall and 0.63 (95% CI, 0.58 to 0.68) among women younger than 40 years. These measures were almost identical in the model based on estrogen receptor–specific relative risks and attributable risks. CONCLUSION Discriminatory accuracy of the new model was similar to that of the most frequently used questionnaire-based breast cancer risk prediction models in White women, suggesting that effective risk stratification for Black women is now possible. This model may be especially valuable for risk stratification of young Black women, who are below the ages at which breast cancer screening is typically begun.

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