scholarly journals Use of Low-Dose Tamoxifen to Increase Mammographic Screening Sensitivity in Premenopausal Women

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 302
Author(s):  
Mikael Eriksson ◽  
Kamila Czene ◽  
Emily F. Conant ◽  
Per Hall
Keyword(s):  
Relative Density ◽  
Mammographic Density ◽  
Breast Density ◽  
Tumor Size ◽  
Low Dose ◽  
Premenopausal Women ◽  
Mammographic Screening ◽  
Interval Cancers ◽  
Dense Tissue ◽  
Screening Sensitivity

Increased breast density decreases mammographic sensitivity due to masking of cancers by dense tissue. Tamoxifen exposure reduces mammographic density and, therefore, should improve screening sensitivity. We modelled how low-dose tamoxifen exposure could be used to increase mammographic sensitivity. Mammographic sensitivity was calculated using the KARMA prospective screening cohort. Two models were fitted to estimate screening sensitivity and detected tumor size based on baseline mammographic density. BI-RADS-dependent sensitivity was estimated. The results of the 2.5 mg tamoxifen arm of the KARISMA trial were used to define expected changes in mammographic density after six months exposure and to predict changes in mammographic screening sensitivity and detected tumor size. Rates of interval cancers and detection of invasive tumors were estimated for women with mammographic density relative decreases by 10–50%. In all, 517 cancers in premenopausal women were diagnosed in KARMA: 287 (56%) screen-detected and 230 (44%) interval cancers. Screening sensitivities prior to tamoxifen, were 76%, 69%, 53%, and 46% for BI-RADS density categories A, B, C, and D, respectively. After exposure to tamoxifen, modelled screening sensitivities were estimated to increase by 0% (p = 0.35), 2% (p < 0.01), 5% (p < 0.01), and 5% (p < 0.01), respectively. An estimated relative density decrease by ≥20% resulted in an estimated reduction of interval cancers by 24% (p < 0.01) and reduction in tumors >20 mm at detection by 4% (p < 0.01). Low-dose tamoxifen has the potential to increase mammographic screening sensitivity and thereby reduce the proportion of interval cancers and larger screen-detected cancers.

scholarly journals Tumour Size at Detection According to Different Measures of Mammographic Breast Density

2009 ◽  
Vol 16 (3) ◽  
pp. 140-146 ◽  
Author(s):  
Carolyn Nickson ◽  
Anne M Kavanagh
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Tumour Size ◽  
Mammographic Screening ◽  
Cancer Prognosis ◽  
Mammographic Breast Density ◽  
Interval Cancers ◽  
Dense Area ◽  
Screening Strategies ◽  
Continuous Measures

Objectives Breast cancer prognosis is better for smaller tumours. Women with high breast density are at higher risk of breast cancer and have larger screen-detected and interval cancers in mammographic screening programmes. We assess which continuous measures of breast density are the strongest predictors of breast tumour size at detection and therefore the best measures to identify women who might benefit from more intensive mammographic screening or alternative screening strategies. Setting and methods We compared the association between breast density and tumour size for 1007 screen-detected and 341 interval cancers diagnosed in an Australian mammographic screening programme between 1994 and 1996, for three semi-automated continuous measures of breast density: per cent density, dense area and dense area adjusted for non-dense area. Results After adjustment for age, hormone therapy use, family history of breast cancer and mode of detection (screen-detected or interval cancers), all measures of breast density shared a similar positive and significant association with tumour size. For example, tumours increased in size with dense area from an estimated mean 2.2 mm larger in the second quintile (β = 2.2; 95% Cl 0.4–3.9, P < 0.001) to mean 6.6 mm larger in the highest decile of dense area (β = 6.6; 95% Cl 4.4–8.9, P < 0.001), when compared with first quintile of breast density. Conclusions Of the breast density measures assessed, either dense area or per cent density are suitable measures for identifying women who might benefit from more intensive mammographic screening or alternative screening strategies.

Screening Sensitivity According to Breast Cancer Location

2019 ◽  
Vol 70 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Isabelle Théberge ◽  
Marie-Hélène Guertin ◽  
Nathalie Vandal ◽  
Gary Côté ◽  
Michel-Pierre Dufresne ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Central Area ◽  
Lower Sensitivity ◽  
Interval Cancers ◽  
Experienced Radiologist ◽  
Sensitivity Ratio ◽  
Screening Mammograms ◽  
Screening Sensitivity ◽  
Adjusted Sensitivity

Purpose To examine the relation between breast cancer location and screening mammogram sensitivity, and assess whether this association is modified by body mass index (BMI) or breast density. Methods This study is based on all interval cancers (n = 481) and a random sample of screen-detected cancers (n = 481) diagnosed in Quebec Breast Cancer Screening Program participants in 2007. Film-screening mammograms, diagnostic mammograms, and ultrasound reports (when available) were requested for these cases. The breast cancer was then localised in mediolateral oblique (MLO) and craniocaudal (CC) projections of the breast by 1 experienced radiologist. The association between cancer location and screening sensitivity was assessed by logistic regression. Adjusted sensitivity and sensitivity ratios were obtained by marginal standardisation. Results A total of 369 screen-detected and 268 interval cancers could be localised in MLO and/or CC projections. The 2-year sensitivity reached 68%. Overall, sensitivity was not statistically associated with location of the cancer. However, sensitivity seems lower in MLO posterior inferior area for women with BMI ≥ 25 kg/m2 compared to sensitivity in central area for women with lower BMI (adjusted sensitivity ratio: 0.58, 95% confidence interval [CI]: 0.17–0.98). Lower sensitivity was also observed in subareolar areas for women with breast density ≥ 50% compared to the central areas for women with lower breast density (for MLO and CC projections, adjusted sensitivity ratio and 95% CI of, respectively, 0.54 [0.13–0.96] and 0.46 [0.01–0.93]). Conclusions Screening sensitivity seems lower in MLO posterior inferior area in women with higher BMI and in subareolar areas in women with higher breast density. When interpreting screening mammograms, radiologists need to pay special attention to these areas.

scholarly journals Development of a Quantitative Estimation of Mammographically Breast Density

2017 ◽  
Vol 18 (1) ◽  
pp. 16-20
Author(s):  
Meherun Nahar ◽  
Abdus Sattar Mollah ◽  
Mir Mohammad Akramuzzaman
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Breast Density ◽  
Quantitative Estimation ◽  
Mammographic Breast Density ◽  
Computer Assisted ◽  
Image Analyzer ◽  
Oblique View ◽  
Language Version ◽  
Dense Tissue

Objective: Increased mammographic breast density is a moderate independent risk factor for breast cancer. Assessment of breast density may become useful in risk assessment and prevention decisions. To evaluate the association between mammographic density and breast cancer risk, a simple observer-assisted technique called interactive thresholding was developed.Methods: For providing, a quantitative estimation of mammographically dense tissue, in this study computer assisted measurements were carried out using Adobe AIR software. For thresholding technique, software named ‘Xray Image Analyzer’ was programmed in Adobe AIR language version - Action script 3.0. runtime version- Flash player 9, AIR 1.0, and flash Lite-4. Interactive thresholding technique was applied to digitized film screen mammograms, which assesses the proportion of radio graphically dense tissue in the mammographic image representing mammographic density. The technique evaluated for 36 mammograms of 18 women who underwent referral mammography in a hospital at Dhaka city from October 2010 to October 2011.Results: The women in the selected group were in age range of 20 to 60 years, with a mean age of 44±9 and median age is 45 yrs. The technique was found to be very reliable with an intra-class correlation coefficient between observers typically R = 0.887. This technique may have a role in routine mammographic analysis for the purpose of assessing risk categories and as a tool in studies of the etiology of breast cancer, in particular for monitoring changes in breast parenchyma during potential preventive interventions. Conclusion: It is possible to use the interactive segmentation technique for other projections of the breast, such as the medio-lateral oblique view. In this case, however, it is necessary to perform a manual segmentation to remove the image of the pectoral muscle from the analysis. This technique can be employ as a tool in many clinical studies.Bangladesh J. Nuclear Med. 18(1): 16-20, January 2015

scholarly journals Random effects tumour growth models for identifying image markers of mammography screening sensitivity

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Linda Abrahamsson ◽  
Maya Alsheh Ali ◽  
Kamila Czene ◽  
Gabriel Isheden ◽  
Per Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Growth Model ◽  
Statistical Power ◽  
Large Scale ◽  
Tumour Growth ◽  
Percentage Mammographic Density ◽  
Dense Tissue ◽  
Screening Sensitivity ◽  
Tumour Growth Model

AbstractIntroductionPercentage mammographic density has long been recognised as a marker of breast cancer risk and of mammography sensitivity. There may be other image markers of screening sensitivity and efficient statistical approaches would be helpful for establishing them from large scale epidemiological and screening data.MethodsWe compare a novel random effects continuous tumour growth model (which includes a screening sensitivity submodel) to logistic regression (with interval vs. screen-detected cancer as the dependent variable) in terms of statistical power to detect image markers of screening sensitivity. We do this by carrying out a simulation study. We also use continuous tumour growth modelling to quantify the roles of dense tissue scatter (measured as skewness of the intensity gradient) and percentage mammographic density in screening sensitivity. This is done by using mammograms and information on tumour size, mode of detection and screening history from 1,845 postmenopausal women diagnosed with invasive breast cancer, in Sweden between 1993 and 1995.ResultsThe statistical power to detect a marker of screening sensitivity was larger for our continuous tumour growth model than it was for logistic regression. For the settings considered in this paper, the percentage increase in power ranged from 34 to 56%. In our analysis of data from Swedish breast cancer patients, using our continuous growth model, when including both percentage mammographic density and dense tissue scatter in the screening sensitivity submodel, only the latter variable was significantly associated with sensitivity. When included one at a time, both markers were significantly associated (p-values of 5.7 × 10−3 and 1.0 × 10−5 for percentage mammographic density and dense tissue scatter, respectively).ConclusionsOur continuous tumour growth model is useful for finding image markers of screening sensitivity and for quantifying their role, using large scale epidemiological and screening data. Clustered dense tissue is associated with low mammography screening sensitivity.

scholarly journals Prognostic Effect of Circulating Adiponectin in a Randomized 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide in Premenopausal Women at Risk for Breast Cancer

2012 ◽  
Vol 30 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Debora Macis ◽  
Sara Gandini ◽  
Aliana Guerrieri-Gonzaga ◽  
Harriet Johansson ◽  
Paolo Magni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Insulin Sensitivity ◽  
Mammographic Density ◽  
Low Dose ◽  
Premenopausal Women ◽  
Intraepithelial Neoplasia ◽  
Model Assessment ◽  
Homa Index ◽  
Prognostic Effect

Adipokines are linked to obesity and insulin sensitivity and have recently been related to breast cancer risk and prognosis. We investigated the associations of plasma leptin and adiponectin with mammographic density and disease status and assessed their prognostic effect on recurrence-free survival in premenopausal women at risk for breast cancer.Patients and MethodsWe measured circulating lipids, insulin-like growth factor 1, glucose, insulin and insulin sensitivity (calculated by homeostasis model assessment [HOMA] index), leptin, adiponectin, and leptin-to-adiponectin ratio in 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), intraepithelial neoplasia (n = 160), or 5-year Gail risk of 1.3% or greater (n = 54) who participated in a 2 × 2 trial of low-dose tamoxifen, fenretinide, both agents, or placebo over a 2-year period.ResultsAt baseline, adiponectin levels were directly associated with mammographic density and HDL cholesterol and negatively associated with leptin, leptin-to-adiponectin ratio, body mass index (BMI), and HOMA index. Median adiponectin levels were lower in affected than in unaffected women (P = .006). After a median of 7.2 years and total of 57 breast neoplastic events, there was a 12% reduction in the risk of breast neoplastic events per unit increase of adiponectin (adjusted hazard ratio, 0.88; 95% CI, 0.81 to 0.96; P = .03). There was no interaction between treatment and adiponectin levels.ConclusionLow adiponectin levels are associated with a history of prior intraepithelial neoplasia or pT1mic/pT1a breast cancer and higher risk of second breast neoplastic events in premenopausal women. The associations are independent of BMI, mammographic density, and treatment. Our findings support the role of adiponectin as a potential target for premenopausal breast cancer prevention and treatment.

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

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Adam R. Brentnall ◽  
Ruth Warren ◽  
Elaine F. Harkness ◽  
Susan M. Astley ◽  
Julia Wiseman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Breast Density ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Premenopausal Women ◽  
Density Change ◽  
Percentage Density ◽  
Increased Risk

Abstract 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.

scholarly journals Randomized Double-Blind 2 × 2 Trial of Low-Dose Tamoxifen and Fenretinide for Breast Cancer Prevention in High-Risk Premenopausal Women

2009 ◽  
Vol 27 (23) ◽  
pp. 3749-3756 ◽  
Author(s):  
Andrea Decensi ◽  
Chris Robertson ◽  
Aliana Guerrieri-Gonzaga ◽  
Davide Serrano ◽  
Massimiliano Cazzaniga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Neoplasms ◽  
Mammographic Density ◽  
Low Dose ◽  
Endometrial Thickness ◽  
Premenopausal Women ◽  
Intraepithelial Neoplasia ◽  
Premenopausal Breast Cancer ◽  
Double Blind ◽  
Igf I

Purpose Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial. Patients and Methods A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk ≥ 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years. Results During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% ± 1.0%, 2.1% ± 0.8%, 4.7% ± 1.3%, and 5.2% ± 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen × fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density. Conclusion Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.

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