Publications by authors named "Jack Cuzick"

389 Publications

Adherence to National Guidelines on Cervical Screening: A Population-Based Evaluation from a Statewide Registry.

J Natl Cancer Inst 2021 Aug 31. Epub 2021 Aug 31.

University of New Mexico Comprehensive Cancer Center, Center for HPV Prevention, Albuquerque, USA.

In 2012, national recommendations for cervical-cancer screening of women aged 30-64 years were quinquennial human papillomavirus and cytology co-testing or triennial cytology. Data from a state-wide surveillance program in New Mexico demonstrated 65.2% (95% confidence interval [95%CI]= 64.6%% to 65.7%) of women screened in 2019 had negative co-test within the last 3 years. Percentages of women screened in 2013, 2016, and 2019 with a prior negative co-test more than 5 and up to 7 years ago were 2.6% (95% CI = 2.2% to 2.9%), 2.1% (95% CI = 1.9% to 2.2%), and 6.5% (95% CI = 6.2% to 6.8%), respectively (2-sided P trend<.001). Percentages of women screened in 2013, 2016, and 2019 with a prior negative cytology more than 5 and up to 7 years ago were 3.8% (95% CI = 3.7% to 3.9%), 9.0% (95% CI = 8.7% to 9.3%), and 14.9% (95% CI = 14.4% to 15.4%), respectively (2-sided P trend<.001). Thus, in 2019, only 12.7% (95% CI = 12.4% to 13.1%) of the 30,215 women aged 30-64 years underwent co-testing and 27.7% (95% CI = 27.1% to 28.3%) of the 18,733 underwent cytology at the recommended interval. The observed under- and over-screening could result in increases in cervical-cancer incidence and harms and costs, respectively.
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http://dx.doi.org/10.1093/jnci/djab173DOI Listing
August 2021

The importance of ethnicity: Are breast cancer polygenic risk scores ready for women who are not of White European origin?

Int J Cancer 2021 Aug 30. Epub 2021 Aug 30.

Clinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Polygenic risk scores (PRS) for disease risk stratification show great promise for application in general populations, but most are based on data from individuals of White European origin. We assessed two well validated PRS (SNP18, SNP143) in the Predicting-Risk-of-Cancer-At-Screening (PROCAS) study in North-West England for breast cancer prediction based on ethnicity. Overall, 9475 women without breast cancer at study entry, including 645 who subsequently developed invasive breast cancer or ductal carcinoma in situ provided DNA. All were genotyped for SNP18 and a subset of 1868 controls were genotyped for SNP143. For White Europeans both PRS discriminated well between individuals with and without cancer. For n = 395 Black (n = 112), Asian (n = 119), mixed (n = 44) or Jewish (n = 120) women without cancer both PRS overestimated breast cancer risk, being most marked for women of Black and Jewish origin (P < .001). SNP143 resulted in a potential mean 40% breast cancer risk overestimation in the combined group of non-White/non-European origin. SNP-PRS that has been normalized based on White European ethnicity for breast cancer should not be used to predict risk in women of other ethnicities. There is an urgent need to develop PRS specific for other ethnicities, in order to widen access of this technology.
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http://dx.doi.org/10.1002/ijc.33782DOI Listing
August 2021

Validation of the cell cycle progression score to differentiate indolent from aggressive prostate cancer in men diagnosed through transurethral resection of the prostate biopsy.

Cancer Rep (Hoboken) 2021 Aug 22:e1535. Epub 2021 Aug 22.

Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.

Background: Validation of biomarker-based prognostic models to improve risk stratification in men with localized prostate cancer (PrCa) remains a clinical need. It has previously been shown that the cell cycle progression (CCP) test provides significant, independent prognostic information for men who were incidentally diagnosed with PrCa after transurethral resection of the prostate (TURP) and were conservatively managed.

Aim: The results have been extended in a newly analyzed retrospective cohort of UK men diagnosed through TURP biopsy (TURP1B; N = 305).

Methods And Results: The CCP score was derived from TURP biopsy tissue and combined with a modified UCSF Cancer of the Prostate Risk Assessment score (CAPRA) to generate the clinical cell-cycle risk score (CCR). The primary endpoint was PrCa-specific mortality (PSM). Hazard ratios (HR) were calculated for a one-unit change in score. Median follow-up was 9.6 (IQR: 5.4, 14.1) years, and 67 (22%) men died from PrCa within 10 years of diagnosis. The median CCP score was 1.1 (IQR: 0.6, 1.7). In univariate analyses, CCR proved a significant prognosticator of PSM (HR per unit score change = 2.28; 95% CI: 1.89, 2.74; P = 1.0 × 10 ). In multivariate analyses, CCR remained a significant prognosticator of PSM after adjusting for CAPRA (HR per unit score change = 4.36; 95% CI: 2.65, 7.16; P = 1.3 × 10 ), indicating that its molecular component, CCP, provides significant, independent prognostic information.

Conclusion: These findings validate a combined clinicopathologic and molecular prognostic model for conservatively managed men who are diagnosed through TURP, supporting the use of CCR to inform clinical management.
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http://dx.doi.org/10.1002/cnr2.1535DOI Listing
August 2021

Clinical follow-up practices after cervical cancer screening by co-testing: A population-based study of adherence to U.S. guideline recommendations.

Prev Med 2021 Aug 18;153:106770. Epub 2021 Aug 18.

Center for HPV Prevention, New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.. Electronic address:

Failure to follow-up women after abnormal cervical screening could lead to cervical cancers, yet little is known about adherence to recommended follow-up after abnormal co-testing [cytology and high-risk human papillomavirus (hrHPV) testing]. We documented clinical management following cervical screening by co-testing in a diverse population-based setting. A statewide surveillance program for cervical screening, diagnosis, and treatment was used to investigate all cytology, hrHPV and biopsy reports in the state of New Mexico from January 2015 through August 2019. Guideline-adherent follow-up after co-testing required 1) biopsy within 6 months for low-grade cytology if positive for hrHPV, for high-grade cytology irrespective of hrHPV, and for HPV 16/18 positive results irrespective of cytology and; 2) repeat co-testing within 18 months if cytology was negative and hrHPV test was positive (excluding types 16/18). Screening co-tests (2015-2017) for 164,522 women were analyzed using descriptive statistics, Kaplan Meier curves, and pairwise comparisons between groups. Guideline adherence was highest when both cytology and hrHPV tests were abnormal, ranging from 61.7% to 80.3%. Guideline-adherent follow-up was lower for discordant results. Women with high-grade cytology were less likely to receive a timely biopsy when hrHPV-testing was negative (48.1%) versus positive (83.3%) (p < 0.001). Only 47.9% of women received biopsies following detection of HPV16/18 with normal cytology, and 30.8% received no follow-up within 18-months. Among women with hrHPV-positive normal cytology without evidence of HPV 16/18 infection, 51% received no follow-up within 18 months. Provider education and creation of robust recall systems may help ensure appropriate follow-up of abnormal screening results.
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http://dx.doi.org/10.1016/j.ypmed.2021.106770DOI Listing
August 2021

Prognostic and Predictive Value of HER2 Expression in Ductal Carcinoma : Results from the UK/ANZ DCIS Randomized Trial.

Clin Cancer Res 2021 Aug 11. Epub 2021 Aug 11.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Purpose: HER2 is overexpressed more frequently in ductal carcinoma (DCIS) than in invasive breast cancer but its prognostic significance and predictive role for radiotherapy has not been clearly established. We investigated the prognostic and predictive value of HER2 overexpression in DCIS.

Experimental Design: HER2 expression was evaluated by IHC using the HercepTest™ in samples from UK/ANZ DCIS trial participants ( = 755) with IHC 3+ expression categorized as HER2 positive for primary analyses. Sensitivity analyses included HER2 categorization as negative (IHC 0,1+), equivocal (IHC 2+), and positive (IHC 3+) and analyses restricted to a nested case-control component where 181 cases (with recurrence) were matched to 362 controls by treatment arm and age.

Results: Two-hundred and forty-five (34.4%) of evaluable 713 samples [181 ipsilateral breast events (IBE)] were HER2 positive. HER2 overexpression was associated with significantly increased risk of IBE [HR = 2.29; 95% confidence interval (95% CI), 1.64-3.14; < 0.0001] and IBE (DCIS-IBE; HR = 2.90; 95% CI, 1.91-4.40; < 0.0001), but not of invasive IBE (I-IBE; HR = 1.40; 95% CI, 0.81-2.42; = 0.23; = 0.04). Inclusion of HER2 significantly improved [Δ (1d.f.) 12.25; = 0.0005] a prognostic model of clinicopathological and treatment variables, HER2 being an independent predictor of IBE (multivariate HR = 1.91; 95% CI, 1.33-2.76; = 0.0004). Radiotherapy benefit in preventing DCIS-IBE was significantly greater ( = 0.04) in HER2-positive DCIS (HR = 0.16; 95% CI, 0.07-0.41) compared with HER2-negative DCIS (HR = 0.58; 95% CI, 0.28-1.19).

Conclusions: HER2 overexpression is associated with significantly increased risk of recurrence and is also predictive of radiotherapy benefit, with greater reductions in but not invasive recurrences in HER2-positive DCIS.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1239DOI Listing
August 2021

Performance of an affordable urine self-sampling method for human papillomavirus detection in Mexican women.

PLoS One 2021 21;16(7):e0254946. Epub 2021 Jul 21.

Facultad de Medicina, Centro de Investigación en Políticas, Población y Salud, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Introduction: Urine self-sampling for human papillomavirus (HPV)-based cervical cancer screening is a non-invasive method that offers several logistical advantages and high acceptability, reducing barriers related to low screening coverage. This study developed and evaluated the performance of a low-cost urine self-sampling method for HPV-testing and explored the acceptability and feasibility of potential implementation of this alternative in routine screening.

Methods: A series of sequential laboratory assays examined the impact of several pre-analytical conditions for obtaining DNA from urine and subsequent HPV detection. Initially, we assessed the effect of ethylaminediaminetetraacetic acid (EDTA) as a DNA preservative examining several variables including EDTA concentration, specimen storage temperature, time between urine collection and DNA extraction, and first-morning micturition versus convenience sample collection. We further evaluated the agreement of HPV-testing between urine and clinician-collected cervical samples among 95 women. Finally, we explored the costs of self-sampling supplies as well as the acceptability and feasibility of urine self-sampling among women and healthcare workers.

Results: Our results revealed higher DNA concentrations were obtained when using a 40mM EDTA solution, storing specimens at 25°C and extracting DNA within 72 hrs. of urine collection, regardless of using first-morning micturition or a convenience sampling. We observed good agreement (Kappa = 0.72) between urine and clinician-collected cervical samples for HPV detection. Furthermore, urine self-sampling was an affordable method (USD 1.10), well accepted among cervical cancer screening users, healthcare workers, and decision-makers.

Conclusion: These results suggest urine self-sampling is feasible and appropriate alternative for HPV-testing in HPV-based screening programs in lower-resource contexts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254946PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294492PMC
July 2021

Uptake of co-testing with HPV and cytology for cervical screening: A population-based evaluation in the United States.

Gynecol Oncol 2021 Sep 10;162(3):555-559. Epub 2021 Jul 10.

UNM Health Sciences Center (HSC), Department of Pathology, Albuquerque, NM, USA; UNM Comprehensive Cancer Center, Center for HPV Prevention, Albuquerque, NM, USA. Electronic address:

Objectives: Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we document the state-wide uptake of co-testing with HPV and cytology in women aged 30-64 years as recommended by national and international bodies.

Methods: Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21-64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology.

Results: A total of 1,704,055 cervical screening tests from 681,440 women aged 21-64 years in the state of New Mexico were identified. The proportion of screening tests which were co-tests rose from 5.6% in 2008 to 84.3% in 2019 among women aged 30-64 years with a marked change from the near exclusive use of the Hybrid Capture II HPV test, (a signal amplified test method) to the use of target amplified HPV tests. The largest increases were seen between 2013 and 2015, reflecting the introduction and adoption of new clinical guidelines. Increases in co-testing were also seen in younger women.

Conclusions: Co-testing is now well established in women aged 30-64 years, but smaller increases have also been seen at younger ages, although this is not currently recommended. The impact of co-testing on cervical disease outcomes and number of colposcopies and biopsies in routine population settings remain important, especially in young women.
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http://dx.doi.org/10.1016/j.ygyno.2021.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405560PMC
September 2021

The Relationship between Body Mass Index and Mammographic Density during a Premenopausal Weight Loss Intervention Study.

Cancers (Basel) 2021 Jun 29;13(13). Epub 2021 Jun 29.

Nightingale Breast Screening Centre & Prevent Breast Cancer Unit, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LT, UK.

We evaluated the association between short-term change in body mass index (BMI) and breast density during a 1 year weight-loss intervention (Manchester, UK). We included 65 premenopausal women (35-45 years, ≥7 kg adult weight gain, family history of breast cancer). BMI and breast density (semi-automated area-based, automated volume-based) were measured at baseline, 1 year, and 2 years after study entry (1 year post intervention). Cross-sectional (between-women) and short-term change (within-women) associations between BMI and breast density were measured using repeated-measures correlation coefficients and multivariable linear mixed models. BMI was positively correlated with dense volume between-women ( = 0.41, 95%CI: 0.17, 0.61), but less so within-women ( = 0.08, 95%CI: -0.16, 0.28). There was little association with dense area (between-women = -0.12, 95%CI: -0.38, 0.16; within-women = 0.01, 95%CI: -0.24, 0.25). BMI and breast fat were positively correlated (volume: between = 0.77, 95%CI: 0.69, 0.84, within = 0.58, 95%CI: 0.36, 0.75; area: between = 0.74, 95%CI: 0.63, 0.82, within = 0.45, 95%CI: 0.23, 0.63). Multivariable models reported similar associations. Exploratory analysis suggested associations between BMI gain from 20 years and density measures (standard deviation change per +5 kg/m BMI: dense area: +0.61 (95%CI: 0.12, 1.09); fat volume: -0.31 (95%CI: -0.62, 0.00)). Short-term BMI change is likely to be positively associated with breast fat, but we found little association with dense tissue, although power was limited by small sample size.
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http://dx.doi.org/10.3390/cancers13133245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269424PMC
June 2021

A Novel Automated Immunoassay Platform to Evaluate the Association of Adiponectin and Leptin Levels with Breast Cancer Risk.

Cancers (Basel) 2021 Jun 30;13(13). Epub 2021 Jun 30.

Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.

Adiponectin and leptin are adipokines secreted by the adipose tissue that are associated with several chronic diseases including cancer. We aimed to compare the immunoassay platform ELLA with an enzyme-linked immunosorbent assay (ELISA) kit and to assess whether the results of the association analyses with breast cancer risk were dependent on the assay used. We measured adiponectin and leptin with ELLA and ELISA on baseline serum samples of 116 Italian postmenopausal women enrolled in two international breast cancer prevention trials. Results were compared with Deming, Passing-Bablok regression and Bland-Altman plots. Disease-free survival was analyzed with the Cox model. There was a good correlation between the methods for adiponectin and leptin (r > 0.96). We found an increased breast cancer risk for very low adiponectin levels (HR for ELLA = 3.75; 95% CI: 1.37;10.25, = 0.01), whereas no significant association was found for leptin levels. The disease-free survival curves were almost identical for values obtained with the two methods, for both biomarkers. The ELLA platform showed a good concordance with ELISA for adiponectin and leptin measurements. Our results support the association of very low adiponectin levels with postmenopausal breast cancer risk, irrespective of the method used. The ELLA platform is a time-saving system with high reproducibility, therefore we recommend its use for biomarker assessment.
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http://dx.doi.org/10.3390/cancers13133303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268385PMC
June 2021

Burden of Mycoplasma genitalium and bacterial co-infections in a population-based sample in New Mexico.

Sex Transm Dis 2021 May 14. Epub 2021 May 14.

Department of Obstetrics and Gynecology, Gødstrup Hospital, Gl. Landevej 61, 7400 Herning, Denmark Department of Clinical Medicine, Aarhus University, Palle Juul Jensens Boulevard 99, 8200 Aarhus N, Denmark Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark Department of Epidemiology and Public Health, University of Maryland School of Medicine, 660 W. Redwood St, Howard Hall 102-B, Baltimore, MD 21201, USA Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK Department of Pathology, University of New Mexico Health Sciences Center, MSC02-1670 House of Prevention Epidemiology, Albuquerque, NM 87131, USA Department of Obstetrics and Gynecology, University of New Mexico Health Sciences Center, MSC02-1670 House of Prevention Epidemiology, Albuquerque, NM 87131, USA.

Abstract: In this population-based US study, the overall prevalence of Mycoplasma genitalium was 1.95% (95% CI 1.62-2.34), declining from 6.12% (95% CI 4.72 to 7.92) in women aged 21-24 to 0.48% (95% CI 0.25-0.94) in women aged 40-64. The prevalence of co-infections with Chlamydia trachomatis and Trichomonas vaginalis was low.
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http://dx.doi.org/10.1097/OLQ.0000000000001472DOI Listing
May 2021

Interdisciplinary Approaches to COVID-19.

Adv Exp Med Biol 2021 ;1318:923-936

Universal Scientific Education and Research Network (USERN), The World, Tehran, Iran.

The coronavirus disease 2019 (COVID-19) pandemic has been a significant concern worldwide. The pandemic has demonstrated that public health issues are not merely a health concern but also affect society as a whole. In this chapter, we address the importance of bringing together the world's scientists to find appropriate solutions for controlling and managing the COVID-19 pandemic. Interdisciplinary cooperation, through modern scientific methods, could help to handle the consequences of the pandemic and to avoid the recurrence of future pandemics.
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http://dx.doi.org/10.1007/978-3-030-63761-3_52DOI Listing
May 2021

Improving estimation of Parkinson's disease risk-the enhanced PREDICT-PD algorithm.

NPJ Parkinsons Dis 2021 Apr 1;7(1):33. Epub 2021 Apr 1.

Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

We previously reported a basic algorithm to identify the risk of Parkinson's disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD and used tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as "intermediate" markers of prodromal PD in the absence of sufficient incident cases. We have now developed and tested an enhanced algorithm which incorporates the intermediate markers into the risk model. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort. The enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (93-609-fold difference between the 10th and 90th centiles vs 10-13-fold respectively). There was a greater increase in the risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.75 [95% CI 1.68-4.50; p < 0.001] versus 1.47 [95% CI 0.86-2.51; p = 0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R = 0.164, p = 0.005 vs R = 0.043, p = 0.17). Incorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm.
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http://dx.doi.org/10.1038/s41531-021-00176-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017005PMC
April 2021

Prognostic Value of ER and PgR Expression and the Impact of Multi-clonal Expression for Recurrence in Ductal Carcinoma : Results from the UK/ANZ DCIS Trial.

Clin Cancer Res 2021 May 16;27(10):2861-2867. Epub 2021 Mar 16.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.

Purpose: The prognostic value of estrogen receptor (ER)/progesterone receptor (PgR) expression in ductal carcinoma (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS.

Experimental Design: Formalin-fixed paraffin embedded tissues were collected from UK/ANZ DCIS trial participants ( = 755), and ER/PgR expression was evaluated by IHC in 181 cases (with recurrence) matched to 362 controls by treatment arm and age. Assays were scored by the Allred method and by a newly devised clonal method-analyses categorizing multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed.

Results: ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared with DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of IBE [OR 4.99; 95% confidence interval (CI), 2.66-9.36; < 0.0001], but the risk of invasive IBE was not significantly higher (OR 1.72; 95% CI, 0.84-3.53; = 0.14), = 0.03. ER was an independent predictor in multivariate analyses (OR 2.66; 95% CI, 1.53-4.61). PgR status did not add to the prognostic information provided by ER.

Conclusions: ER expression is a strong predictor of ipsilateral recurrence risk in DCIS. ER-positive DCIS with distinct ER-negative clones has a recurrence risk similar to ER-negative DCIS. ER should be routinely assessed in DCIS, and ER scoring should take clonality of expression into account.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611296PMC
May 2021

Consistency of the S5 DNA methylation classifier in formalin-fixed biopsies versus corresponding exfoliated cells for the detection of pre-cancerous cervical lesions.

Cancer Med 2021 04 12;10(8):2668-2679. Epub 2021 Mar 12.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.

Methylation biomarkers are promising tools for diagnosis and disease prevention. The S5 classifier is aimed at the prevention of cervical cancer by the early detection of cervical intraepithelial neoplasia (CIN). S5 is based on pyrosequencing a promoter region of EPB41L3 and five late regions of HPV types 16, 18, 31, and 33 following bisulfite conversion of DNA. Good biomarkers should perform well in a variety of sample types such as exfoliated cells, fresh frozen or formalin-fixed paraffin-embedded (FFPE) materials. Here, we tested the performance of S5 on 315 FFPE biopsies with paired exfoliated cervical samples using four different conversion kits (Epitect Bisulfite, Epitect Fast Bisulfite, EZ DNA Methylation, and EZ DNA Methylation-Lightning). The S5 values from FFPE biopsies for all kits were significantly correlated with those obtained from their paired exfoliated cells. For the EZ DNA Methylation kit, we observed an average increased methylation of 4.4% in FFPE. This was due to incomplete conversion of DNA (73% for FFPE vs. 95% for cells). The other kits had a DNA conversion rate in FFPE similar to the cells (95%-97%). S5 performed well at discriminating
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http://dx.doi.org/10.1002/cam4.3849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026949PMC
April 2021

The impact of body mass index on breast cancer incidence among women at increased risk: an observational study from the International Breast Intervention Studies.

Breast Cancer Res Treat 2021 Jul 3;188(1):215-223. Epub 2021 Mar 3.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.

Background: We investigated the association between body mass index (BMI) and breast cancer risk in women at increased risk of breast cancer receiving tamoxifen or anastrozole compared with placebo using data from the International Breast Cancer Intervention Studies [IBIS-I (tamoxifen) and IBIS-II (anastrozole)].

Methods: Baseline BMI was calculated from nurse assessed height and weight measurements for premenopausal (n = 3138) and postmenopausal (n = 3731) women in IBIS-I and postmenopausal women in IBIS-II (n = 3787). The primary endpoint was any breast cancer event (invasive and ductal carcinoma in situ). We used Cox proportional hazards regression to calculate hazard ratios (HRs) for risk after adjustment for covariates.

Results: There were 582 (IBIS-I) and 248 (IBIS-II) breast cancer events [median follow-up = 16.2 years (IQR 14.4-17.7) and 10.9 years (IQR 8.8-13.0), respectively]. In adjusted analysis, women with a higher BMI had an increased breast cancer risk in both IBIS-I [HR = 1.06 per 5 kg/m (0.99-1.15), p = 0.114] and in IBIS-II [HR per 5 kg/m = 1.21 (1.09-1.35), p < 0.001]. In IBIS-I, the association between BMI and breast cancer risk was positive in postmenopausal women [adjusted HR per 5 kg/m = 1.14 (1.03-1.26), p = 0.01] but not premenopausal women [adjusted HR per 5 kg/m = 0.97 (0.86-1.09), p = 0.628]. There was no interaction between BMI and treatment group for breast cancer risk in either IBIS-I (p = 0.62) or IBIS-II (p = 0.55).

Conclusions: Higher BMI is associated with greater breast cancer risk in postmenopausal women at increased risk of the disease, but no effect was observed in premenopausal women. The lack of interaction between BMI and treatment group on breast cancer risk suggests women are likely to experience benefit from preventive therapy regardless of their BMI. Trial registration Both trials were registered [IBIS-I: ISRCTN91879928 on 24/02/2006, retrospectively registered ( http://www.isrctn.com/ISRCTN91879928 ); IBIS-II: ISRCTN31488319 on 07/01/2005, retrospectively registered ( http://www.isrctn.com/ISRCTN31488319 )].
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http://dx.doi.org/10.1007/s10549-021-06141-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233270PMC
July 2021

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®.

NPJ Breast Cancer 2021 Feb 12;7(1):15. Epub 2021 Feb 12.

Clinical Trials and Statistics Unit (ICR-CTSU), Division of Clinical Studies, The Institute of Cancer Research, London, UK.

Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2- breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (r(RS) = 0.96, 95% CI 0.93-0.97 with level of agreement (LoA) of -7.69 to 8.12; r(EP) = 0.97, 95% CI 0.96-0.98 with LoA of -0.64 to 1.26 and r(ROR) = 0.97 (95% CI 0.94-0.98) with LoA of -8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.
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http://dx.doi.org/10.1038/s41523-021-00216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881187PMC
February 2021

A Randomized Comparison of Different Vaginal Self-sampling Devices and Urine for Human Papillomavirus Testing-Predictors 5.1.

Cancer Epidemiol Biomarkers Prev 2021 04 29;30(4):661-668. Epub 2021 Jan 29.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom.

Background: Human papillomavirus (HPV)-based screening is rapidly replacing cytology as the cervical screening modality of choice. In addition to being more sensitive than cytology, it can be done on self-collected vaginal or urine samples. This study will compare the high-risk HPV positivity rates and sensitivity of self-collected vaginal samples using four different collection devices and a urine sample.

Methods: A total of 620 women referred for colposcopy were invited to provide an initial stream urine sample collected with the Colli-Pee device and take two vaginal self-samples, using either a dry flocked swab (DF) and a wet dacron swab (WD), or a HerSwab (HS) and Qvintip (QT) device. HPV testing was performed by the BD Onclarity HPV Assay.

Results: A total of 600 vaginal sample pairs were suitable for analysis, and 505 were accompanied by a urine sample. Similar positivity rates and sensitivities for CIN2+ and CIN3+ were seen for DF, WD, and urine, but lower values were seen for QT and HS. No clear user preferences were seen between devices, but women found urine easiest to collect, and were more confident they had taken the sample correctly. The lowest confidence in collection was reported for HS.

Conclusions: Urine, a DF swab, and WD swab all performed well and were well received by the women, whereas the Qvintip and HerSwab devices were less satisfactory.

Impact: This is the first study to compare five self-sampling methods in the same women taken at the same time. It supports wider use of urine or vaginal self-sampling for cervical screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611176PMC
April 2021

Off-treatment bone mineral density changes in postmenopausal women receiving anastrozole for 5 years: 7-year results from the IBIS-II prevention trial.

Br J Cancer 2021 04 22;124(8):1373-1378. Epub 2021 Jan 22.

Department of Oncology and Metabolism, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.

Background: Anastrozole has been associated with substantial accelerated bone mineral density (BMD) loss during active treatment.

Methods: One thousand four hundred and ten women were included in a BMD substudy and stratified into three strata according to their baseline T-score at spine or femoral neck. The primary objective of this analysis was to investigate whether DXA BMD at the spine and hip changed two years after treatment cessation (between years 5 and 7) in those who did not receive risedronate.

Results: Five- and seven-year BMD data were available for a total of 528 women who did not receive risedronate. In women with normal BMD at baseline, an increase in BMD at the lumbar spine after anastrozole withdrawal was observed 1.25% (95% CI 0.73 to 1.77) (P = 0.0004), which was larger than in those on placebo (0.14% (-0.29 to 0.56))). At the hip, BMD remained unchanged between years 5 and 7 for those previously on anastrozole but continued to a decrease in those who had been randomised to placebo (-1.35% (-1.70 to -0.98)).

Conclusions: These are the first results reporting BMD changes after stopping anastrozole in a breast cancer prevention setting. Our results show that the negative effects of anastrozole on BMD in the preventive setting are partially reversible.
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http://dx.doi.org/10.1038/s41416-020-01228-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039042PMC
April 2021

Determinants of Human Papillomavirus Vaccine Uptake by Adult Women Attending Cervical Cancer Screening in 9 European Countries.

Am J Prev Med 2021 04 24;60(4):478-487. Epub 2020 Dec 24.

Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain; Faculty of Health Sciences, Universitat Oberta de Catalunya (UOC), Barcelona, Spain.

Introduction: Human papillomavirus-vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated.

Study Design: This was an intervention study.

Setting/participants: Study participants were women aged 25-45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018.

Intervention: Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination.

Main Outcome Measures: Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019.

Results: Among 3,646 participants, 2,748 (range by country=50%-96%) accepted vaccination, and 2,151 (range=30%-93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%-59%) and the need for more information on human papillomavirus vaccines (range=1%-72%). No safety issues were experienced by vaccinated women.

Conclusions: Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings.

Trial Registration: EudraCT Number 2014-003177-42.
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http://dx.doi.org/10.1016/j.amepre.2020.08.032DOI Listing
April 2021

Calibration of CTS5 in Women With Early Estrogen Receptor-Positive Breast Cancer.

J Clin Oncol 2021 02 16;39(4):338-339. Epub 2020 Dec 16.

Mitch Dowsett, PhD, Ralph Lauren Centre for Breast Cancer Research, Royal Marden Hospital, London, UK and Ivana Sestak, PhD and Jack Cuzick, PhD, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.

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http://dx.doi.org/10.1200/JCO.20.02551DOI Listing
February 2021

Adjunctive testing by cytology, p16/Ki-67 dual-stained cytology or HPV16/18 E6 oncoprotein for the management of HPV16/18 screen-positive women.

Int J Cancer 2021 05 22;148(9):2264-2273. Epub 2020 Dec 22.

Faculty of Medine, Research Center on Policies, Population and Health, National Autonomous University of Mexico, Mexico City, Mexico.

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 dual-stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18-positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P < .001), whereas E6 had a sensitivity of 37.8% and a specificity of 83.5%. No invasive cancer was missed by DS or E6, but 75% were in normal cytology. DS test was associated with nearly 75% reduction of colposcopy referrals compared with the direct referral of all HPV16/18-positive women, giving the least number of colposcopies (n = 4.3) per CIN3+ detected. We show that adjunctive testing of HPV16/18-positive women with DS may greatly reduce unnecessary colposcopy referrals within HPV-based screening employing HPV16/18 genotyping while retaining acceptable sensitivity for CIN2+ and CIN3+.
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http://dx.doi.org/10.1002/ijc.33414DOI Listing
May 2021

A case-control study to evaluate the impact of the breast screening programme on mortality in England.

Br J Cancer 2021 02 23;124(4):736-743. Epub 2020 Nov 23.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.

Background: Over the past 30 years since the implementation of the National Health Service Breast Screening Programme, improvements in diagnostic techniques and treatments have led to the need for an up-to-date evaluation of its benefit on risk of death from breast cancer. An initial pilot case-control study in London indicated that attending mammography screening led to a mortality reduction of 39%.

Methods: Based on the same study protocol, an England-wide study was set up. Women aged 47-89 years who died of primary breast cancer in 2010 or 2011 were selected as cases (8288 cases). When possible, two controls were selected per case (15,202 controls) and were matched by date of birth and screening area.

Results: Conditional logistic regressions showed a 38% reduction in breast cancer mortality after correcting for self-selection bias (OR 0.62, 95% CI 0.56-0.69) for women being screened at least once. Secondary analyses by age group, and time between last screen and breast cancer diagnosis were also performed.

Conclusions: According to this England-wide case-control study, mammography screening still plays an important role in lowering the risk of dying from breast cancer. Women aged 65 or over see a stronger and longer lasting benefit of screening compared to younger women.
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http://dx.doi.org/10.1038/s41416-020-01163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884709PMC
February 2021

Tamoxifen related side effects and their impact on breast cancer incidence: A retrospective analysis of the randomised IBIS-I trial.

Breast 2020 Dec 31;54:216-221. Epub 2020 Oct 31.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, Queen Mary University London, London, EC1M 6BQ, UK. Electronic address:

Background: Studies in the adjuvant setting have shown that endocrine therapy related side effects predict breast cancer recurrence risk. Here, we assess the relationship between early reported side effects and incidence of breast cancer in women randomised to tamoxifen for cancer prevention in the International Breast Intervention Study (IBIS)-I trial.

Methods: Women randomised to tamoxifen in the IBIS-I trial and for whom side effect status was known at the 6-month follow-up visit were included in this analysis. Side effects included in this analysis were hot flushes, vaginal discharge, and vaginal dryness. The primary endpoint was all breast cancer and secondary endpoint was oestrogen receptor (ER) positive breast cancer. Cox proportional hazard models were used to investigate breast cancer incidence in the tamoxifen group with and without side effects reported within 6 months of randomisation.

Results: Women randomised to tamoxifen and reporting hot flushes at the 6-month follow-up visit had a non-statistically significant increase in breast cancer compared to those without hot flushes (HR = 1.26 (0.98-1.62), P = 0.08). A significant higher breast cancer risk was observed for postmenopausal women who reported hot flushes at the 6-month follow-up visit compared to those without hot flushes (HR = 1.59 (1.12-2.26), P = 0.01). A higher risk was observed for ER-positive breast cancer in postmenopausal women (HR = 1.81 (1.19-2.74), P = 0.01). No significant associations between gynaecological side effects and breast cancer occurrence was observed.

Conclusions: Overall, no association between side effects reported at 6 months and subsequent breast cancer occurrence was observed. Some side effects might be useful markers for breast cancer occurrence in postmenopausal women.
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http://dx.doi.org/10.1016/j.breast.2020.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649356PMC
December 2020

Molecular Drivers of Onco DX, Prosigna, EndoPredict, and the Breast Cancer Index: A TransATAC Study.

J Clin Oncol 2021 01 27;39(2):126-135. Epub 2020 Oct 27.

The Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, United Kingdom.

Purpose: The Onco DX Recurrence Score (RS), Prosigna Prediction Analysis of Microarray 50 (PAM50) Risk of Recurrence (ROR), EndoPredict (EP), and Breast Cancer Index (BCI) are used clinically for estimating risk of distant recurrence for patients receiving endocrine therapy. Discordances in estimates occur between them. We aimed to identify the molecular features that drive the tests and lead to these differences.

Patients And Methods: Analyses for RS, ROR, EP, and BCI were conducted by the manufacturers in the TransATAC sample collection that consisted of the tamoxifen or anastrozole arms of the ATAC trial. Estrogen receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative cases without chemotherapy treatment were included in which all four tests were available (n = 785). Clinicopathologic features included in some tests were excluded from the comparisons. Estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of variance tests were applied.

Results: There were moderate to strong correlations among the four molecular scores (ρ = 0.63-0.74) except for RS versus ROR (ρ = 0.32) and RS versus BCI (ρ = 0.35). RS had strong negative correlation with its estrogen module (ρ = -0.79) and moderate positive correlation with its proliferation module (ρ = 0.36). RS's proliferation module explained 72.5% of ROR's variance, while the estrogen module explained only 0.6%. Most of EP's and BCI's variation was accounted for by the proliferation module (50.0% and 54.3%, respectively) and much less by the estrogen module (20.2% and 2.7%, respectively).

Conclusion: In contrast to common understanding, RSs are determined more strongly by estrogen-related features and only weakly by proliferation markers. However, the EP, BCI, and particularly ROR scores are determined largely by proliferative features. These relationships help to explain the differences in the prognostic performance of the tests.
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http://dx.doi.org/10.1200/JCO.20.00853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078458PMC
January 2021

Effective methylation triage of HPV positive women with abnormal cytology in a middle-income country.

Int J Cancer 2021 03 24;148(6):1383-1393. Epub 2020 Oct 24.

Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, London, UK.

The S5-methylation test, an alternative to cytology and HPV16/18 genotyping to triage high-risk HPV-positive (hrHPV+) women, has not been widely validated in low-middle-income countries (LMICs). We compared S5 to HPV16/18 and cytology to detect cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) and CIN3+ in hrHPV+ women selected from a randomized pragmatic trial of 2661 Colombian women with an earlier-borderline abnormal cytology. We included all hrHPV+ CIN2 and CIN3+ cases (n = 183) age matched to 183
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http://dx.doi.org/10.1002/ijc.33314DOI Listing
March 2021

Mammographic density change in a cohort of premenopausal women receiving tamoxifen for breast cancer prevention over 5 years.

Breast Cancer Res 2020 09 29;22(1):101. Epub 2020 Sep 29.

Prevent Breast Cancer Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, M23 9LT, UK.

Background: A decrease in breast density due to tamoxifen preventive therapy might indicate greater benefit from the drug. It is not known whether mammographic density continues to decline after 1 year of therapy, or whether measures of breast density change are sufficiently stable for personalised recommendations.

Methods: Mammographic density was measured annually over up to 5 years in premenopausal women with no previous diagnosis of breast cancer but at increased risk of breast cancer attending a family-history clinic in Manchester, UK (baseline 2010-2013). Tamoxifen (20 mg/day) for prevention was prescribed for up to 5 years in one group; the other group did not receive tamoxifen and were matched by age. Fully automatic methods were used on mammograms over the 5-year follow-up: three area-based measures (NN-VAS, Stratus, Densitas) and one volumetric (Volpara). Additionally, percentage breast density at baseline and first follow-up mammograms was measured visually. The size of density declines at the first follow-up mammogram and thereafter was estimated using a linear mixed model adjusted for age and body mass index. The stability of density change at 1 year was assessed by evaluating mean squared error loss from predictions based on individual or mean density change at 1 year.

Results: Analysis used mammograms from 126 healthy premenopausal women before and as they received tamoxifen for prevention (median age 42 years) and 172 matched controls (median age 41 years), with median 3 years follow-up. There was a strong correlation between percentage density measures used on the same mammogram in both the tamoxifen and no tamoxifen groups (all correlation coeficients > 0.8). Tamoxifen reduced mean breast density in year 1 by approximately 17-25% of the inter-quartile range of four automated percentage density measures at baseline, and from year 2, it decreased further by approximately 2-7% per year. Predicting change at 2 years using individual change at 1 year was approximately 60-300% worse than using mean change at 1year.

Conclusions: All measures showed a consistent and large average tamoxifen-induced change in density over the first year, and a continued decline thereafter. However, these measures of density change at 1 year were not stable on an individual basis.
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http://dx.doi.org/10.1186/s13058-020-01340-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523310PMC
September 2020

A state-wide population-based evaluation of cervical cancers arising during opportunistic screening in the United States.

Gynecol Oncol 2020 11 22;159(2):344-353. Epub 2020 Sep 22.

Departments of Pathology and Obstetrics & Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Objective: Despite widespread cervical screening, an estimated 13,800 women will be diagnosed with cervical cancer in the United States in 2020. To inform improvements, the screening histories of women diagnosed with cervical cancer in New Mexico were assessed.

Methods: Data were collected on all cervical screening, diagnostic tests and treatment procedures for all women diagnosed with cervical cancer aged 25-64 yrs. in New Mexico from 2006 to 2016. Women were categorized by their screening attendance in the 5-40 months (screening interval) and 1-4 months (peri-diagnostic interval) prior to cancer diagnosis.

Results: Of the 504 women diagnosed between May 2009-December 2016, 64% were not screened or had only inadequate screening tests in the 5-40 months prior to diagnosis, and 90 of 182 screened women (49%) had only negative screens in this period. Only 32% (N = 162) of cervical cancers were screen-detected. Women with adenocarcinomas were more likely to have had a recent negative screen (41/57 = 722%) than women with squamous cancers (50/112 = 45%). Both older women (aged 45-64 years) and women with more advanced cancers were less likely to have been screened, and if screened, were more likely to have a false-negative outcome. Only 9% of cancers were diagnosed in women who did not attend biopsy or treatment after positive tests requiring clinical management. Screening currently prevents 35% of cancers, whereas full screening coverage could prevent 61% of cervical cancers.

Conclusion: Improved screening coverage has the largest potential for reducing cervical cancer incidence, though there is also a role for improved recall procedures and screening sensitivity.
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http://dx.doi.org/10.1016/j.ygyno.2020.08.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594931PMC
November 2020

Predicting Expected Absolute Chemotherapy Treatment Benefit in Women With Early-Stage Breast Cancer Using EndoPredict, an Integrated 12-Gene Clinicomolecular Assay.

JCO Precis Oncol 2019 6;3. Epub 2019 Aug 6.

Northwestern University, Chicago, IL.

Purpose: Previous studies have shown EndoPredict (EPclin), a test that integrates 12-gene expression data with nodal status and tumor size, to be predictive for risk of distant recurrence in women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer. Here, we modeled expected absolute chemotherapy benefit on the basis of EPclin test results.

Methods: The effect of chemotherapy was modeled using previously validated 10-year risk of distant recurrence as a function of EPclin score for patients treated without chemotherapy. Average relative chemotherapy benefit to reduce breast cancer distant recurrence was evaluated using a published meta-analysis from the Early Breast Cancer Trialists' Collaborative Group. Absolute chemotherapy benefit differences were estimated across a range of interaction strengths between relative chemotherapy benefit and EPclin score. The average absolute benefit was calculated for patients with high and low EPclin scores using the distribution of scores in 2,185 samples tested by Myriad Genetics.

Results: The average expected absolute benefit of chemotherapy treatment for patients with a low EPclin score was 1.8% in the absence of interaction and 1.5% for maximal interaction. Conversely, the expected average absolute chemotherapy benefit for patients with a high EPclin score was 5.3% and 7.3% for no interaction and maximal interaction, respectively.

Conclusion: For women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer, a high EPclin score identified which patients would benefit most from adjuvant chemotherapy in terms of absolute reduction of distant recurrence, regardless of the amount of interaction between EPclin and relative chemotherapy benefit. A high degree of prognostic discrimination for distant recurrence is more important for identifying patients likely to benefit most from chemotherapy than an interaction between EPclin and treatment-relative benefit.
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http://dx.doi.org/10.1200/PO.18.00361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446472PMC
August 2019

Estimated and projected burden of multiple sclerosis attributable to smoking and childhood and adolescent high body-mass index: a comparative risk assessment.

Int J Epidemiol 2021 01;49(6):2051-2057

Department of Neurology, The Royal London Hospital, Barts Health NHS Trust, London, UK.

Background: Smoking and childhood and adolescent high body-mass index (BMI) are leading lifestyle-related risk factors of global premature morbidity and mortality, and have been associated with an increased risk of developing multiple sclerosis (MS). This study aims to estimate and project the proportion of MS incidence that could be prevented with elimination of these risk factors.

Methods: Prevalence estimates of high BMI during childhood/adolescence and smoking in early adulthood, and relative risks of MS, were obtained from published literature. A time-lag of 10 years was assumed between smoking in early adulthood and MS incidence, and a time-lag of 20 years was assumed between childhood/adolescent high BMI and MS incidence. The MS population attributable fractions (PAFs) of smoking and high BMI were estimated as individual and combined risk factors, by age, country and sex in 2015, 2025 and 2035 where feasible.

Results: The combined estimated PAFs for smoking and high BMI in 2015 were 14, 11, 12 and 12% for the UK, USA, Russia and Australia in a conservative estimate, and 21, 20, 19 and 16% in an independent estimate, respectively. Estimates for smoking are declining over time, whereas estimates for high early life BMI are rising. The PAF for high early life BMI is highest in the USA and is estimated to increase to 14% by 2035.

Conclusions: Assuming causality, there is the potential to substantially reduce MS incidence with the elimination of lifestyle-related modifiable risk factors, which are the target of global public health prevention strategies.
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http://dx.doi.org/10.1093/ije/dyaa151DOI Listing
January 2021
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