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  • 1
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 17, No. 12 ( 2008-12-01), p. 3474-3481
    Abstract: Understanding which factors influence mammographically dense and nondense areas is important because percent mammographic density adjusted for age is a strong, continuously distributed risk factor for breast cancer, especially when adjusted for weight or body mass index. Using computer-assisted methods, we measured mammographically dense areas for 571 monozygotic and 380 dizygotic Australian and North American twin pairs ages 40 to 70 years. We used a novel regression modeling approach in which each twin's measure of dense and nondense area was regressed against one or both of the twin's and co-twin's covariates. The nature of changes to regression estimates with the inclusion of the twin and/or co-twin's covariates can be evaluated for consistency with causal and/or other models. By causal, we mean that if it were possible to vary a covariate experimentally then the expected value of the outcome measure would change. After adjusting for the individual's weight, the co-twin associations with weight were attenuated, consistent with a causal effect of weight on mammographic measures, which in absolute log cm2/kg was thrice stronger for nondense than dense area. After adjusting for weight, later age at menarche, and greater height were associated with greater dense and lesser nondense areas in a manner inconsistent with causality. The associations of dense and nondense areas with parity are consistent with a causal effect and/or within-person confounding. The associations between mammographic density measures and height are consistent with shared early life environmental factors that predispose to both height and percent mammographic density and possibly breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3474–81)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 4 ( 2010-02-15), p. 1449-1458
    Abstract: Mammographic density for age and body mass index (BMI) is a heritable risk factor for breast cancer. We aimed to determine if recently identified common variants associated with small gradients in breast cancer risk are associated with mammographic density. We genotyped 497 monozygotic and 330 dizygotic twin pairs and 634 of their sisters from 903 families for 12 independent variants. Mammographic dense area, percent dense area, and nondense area were measured by three observers using a computer-thresholding technique. Associations with mammographic density measures adjusted for age, BMI, and other determinants were estimated (a) cross-sectionally using a multivariate normal model for pedigree analysis (Px), (b) between sibships, and (c) within sibships using orthogonal transformations of outcomes and exposures. A combined test of association (Pc) was derived using the independent estimates from b and c. We tested if the distributions of P values across variants differed from the uniform distribution (Pu). For dense area and percent dense area, the distributions of Pc values were not uniform (both Pu & lt;0.007). Consistent with their breast cancer associations, rs3817198 (LSP1) and rs13281615 (8q) were associated with dense area and percent dense area (all Px and Pc & lt;0.05), and rs889312 (MAP3K1), rs2107425 (H19), and rs17468277 (CASP8) were marginally associated with dense area (some Px or Pc & lt;0.05). All associations were independent of menopausal status. At least two common breast cancer susceptibility variants are associated with mammographic density measures that predict breast cancer. These findings could help elucidate how those variants and mammographic density measures are associated with breast cancer susceptibility. Cancer Res; 70(4); 1449–58
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 410466-3
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  • 3
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 22, No. 12 ( 2013-12-01), p. 2395-2403
    Abstract: Background: Mammographic density, the area of the mammographic image that appears white or bright, predicts breast cancer risk. We estimated the proportions of variance explained by questionnaire-measured breast cancer risk factors and by unmeasured residual familial factors. Methods: For 544 MZ and 339 DZ twin pairs and 1,558 non-twin sisters from 1,564 families, mammographic density was measured using the computer-assisted method Cumulus. We estimated associations using multilevel mixed-effects linear regression and studied familial aspects using a multivariate normal model. Results: The proportions of variance explained by age, body mass index (BMI), and other risk factors, respectively, were 4%, 1%, and 4% for dense area; 7%, 14%, and 4% for percent dense area; and 7%, 40%, and 1% for nondense area. Associations with dense area and percent dense area were in opposite directions than for nondense area. After adjusting for measured factors, the correlations of dense area with percent dense area and nondense area were 0.84 and −0.46, respectively. The MZ, DZ, and sister pair correlations were 0.59, 0.28, and 0.29 for dense area; 0.57, 0.30, and 0.28 for percent dense area; and 0.56, 0.27, and 0.28 for nondense area (SE = 0.02, 0.04, and 0.03, respectively). Conclusions: Under the classic twin model, 50% to 60% (SE = 5%) of the variance of mammographic density measures that predict breast cancer risk are due to undiscovered genetic factors, and the remainder to as yet unknown individual-specific, nongenetic factors. Impact: Much remains to be learnt about the genetic and environmental determinants of mammographic density. Cancer Epidemiol Biomarkers Prev; 22(12); 2395–403. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 4
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 15, No. 4 ( 2006-04-01), p. 612-617
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 15, No. 4 ( 2006-04-01), p. 612-617
    Abstract: Background: Percent mammographic density (PMD) is a risk factor for breast cancer. Our previous twin study showed that the heritability of PMD was 63%. This study determined the heritabilities of the components of PMD, the areas of dense and nondense tissue in the mammogram. Methods: We combined two twin studies comprising 571 monozygous and 380 dizygous twin pairs recruited from Australia and North America. Dense and nondense areas were measured using a computer-assisted method, and information about potential determinants was obtained by questionnaire. Under the assumptions of the classic twin model, we estimated the heritability of the log dense area and log nondense area and the genetic and environmental contributions to the covariance between the two traits, using maximum likelihood theory and the statistical package FISHER. Results: After adjusting for measured determinants, for each of the log dense area and the log nondense area, the monozygous correlations were greater than the dizygous correlations. Heritability was estimated to be 65% (95% confidence interval, 60-70%) for dense area and 66% (95% confidence interval, 61-71%) for nondense area. The correlations (SE) between the two adjusted traits were −0.35 (0.023) in the same individual, −0.26 (0.026) across monozygous pairs, and −0.14 (0.034) across dizygous pairs. Conclusion: Genetic factors may play a large role in explaining variation in the mammographic areas of both dense and nondense tissue. About two thirds of the negative correlation between dense and nondense area is explained by the same genetic factors influencing both traits, but in opposite directions. (Cancer Epidemiol Biomarkers Prev 2006;15(4):612–7)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 5
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 131, No. 2 ( 2012-1), p. 553-559
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2004077-5
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 21, No. 7 ( 2012-07-01), p. 1149-1155
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 7 ( 2012-07-01), p. 1149-1155
    Abstract: Background: Mammographic density is a strong risk factor for breast cancer. It is unknown whether there are different causes of variation in mammographic density at different ages. Methods: Mammograms and questionnaires were obtained on average 8 years apart from 327 Australian female twin pairs (204 monozygous and 123 dizygous). Mammographic dense area and percentage dense area were measured using a computer-assisted method. The correlational structure of the longitudinal twin data was estimated under a multivariate normal model using FISHER. Inference about causation from examination of familial confounding was made by regressing each twin's recent mammographic density measure against one or both of her and her co-twin's past measures. Results: For square root dense area and percentage dense area (age- and body mass index–adjusted), the correlations over time within twins were 0.86 and 0.82, and the cross-twin correlations were 0.71 and 0.65 for monozygous pairs and 0.25 and 0.20 for dizygous pairs, respectively. As a predictor of a twin's recent dense area, the regression coefficient (SE) for the co-twin's past dense area reduced after adjusting for her own past measure from 0.84 (0.03) to 0.09 (0.03) for monozygous pairs and from 0.63 (0.04) to 0.04 (0.03) for dizygous pairs. Corresponding estimates for percentage dense area were 0.73 (0.04), 0.10 (0.03), 0.42 (0.05), and 0.03 (0.03). Conclusion: Mammographic density measures are highly correlated over time and the familial/genetic components of their variation are established before mid-life. Impact: Mammographic density of young women could provide a means for breast cancer control. Cancer Epidemiol Biomarkers Prev; 21(7); 1149–55. ©2012 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 7
    Online Resource
    Online Resource
    Wiley ; 1995
    In:  Medical Journal of Australia Vol. 163, No. 8 ( 1995-10), p. 435-440
    In: Medical Journal of Australia, Wiley, Vol. 163, No. 8 ( 1995-10), p. 435-440
    Type of Medium: Online Resource
    ISSN: 0025-729X , 1326-5377
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 1995
    detail.hit.zdb_id: 2035730-8
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  • 8
    Online Resource
    Online Resource
    Elsevier BV ; 2007
    In:  Pathology Vol. 39, No. 3 ( 2007-06), p. 361-363
    In: Pathology, Elsevier BV, Vol. 39, No. 3 ( 2007-06), p. 361-363
    Type of Medium: Online Resource
    ISSN: 0031-3025
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2007
    detail.hit.zdb_id: 1479244-8
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  • 9
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2008
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 17, No. 10 ( 2008-10-01), p. 2818-2824
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 17, No. 10 ( 2008-10-01), p. 2818-2824
    Abstract: It is possible that the performance of mammographic screening would be improved if it is targeted at women at higher risk of breast cancer or who are more likely to have their cancer missed at screening, through more intensive screening or alternative screening modalities. We conducted a case-control study within a population-based Australian mammographic screening program (1,706 invasive breast cancers and 5,637 randomly selected controls). We used logistic regression to examine the effects of breast density, age, and hormone therapy use, all known to influence both breast cancer risk and the sensitivity of mammographic screening, on the risk of small (≤15 mm) and large ( & gt;15 mm) screen-detected and interval breast cancers. The risk of small screen-detected cancers was not associated with density, but the risk of large screen-detected cancers was nearly 3-fold for the second quintile and approximately 4-fold for the four highest density categories (third and fourth quintiles and the two highest deciles) compared with the lowest quintile. The risk of interval cancers increased monotonically across the density categories [highest decile odds ratio (OR), 4.65; 95% confidence interval (95% CI), 2.96-7.31]. The risk of small and large screen-detected cancers, but not interval cancers, increased with age. After adjusting for age and density, hormone therapy use was associated with a moderately elevated risk of interval cancers (OR, 1.43; 95% CI, 1.12-1.81). The effectiveness of the screening program could be improved if density were to be used to identify women most likely to have poor screening outcomes. There would be little additional benefit in targeting screening based on age and hormone therapy use. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2818–24)
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2008
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2005
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 14, No. 5 ( 2005-05-01), p. 1060-1064
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 14, No. 5 ( 2005-05-01), p. 1060-1064
    Abstract: Objective: We examine to what extent the lower mammographic sensitivity found in hormone replacement therapy (HRT) users can be explained by any association of HRT use with higher mammographic density and more difficult to detect cancers. Methods: We used logistic regression to estimate the odds of a false-negative screen (a breast cancer diagnosed in the 24 months after a negative screening examination) for HRT users and to estimate, and adjust for, mammographic density (measured on a continuous scale, blinded, using a reliable, computer-assisted method), tumor characteristics (size, grade, and morphology), and potential confounders (age, symptom status, family history, and prior screening) among women ages ≥55 years who attended BreastScreen Victoria for first round screening mammography in 1994 and 1995 (1,086 breast cancers) and for subsequent round screening (471 breast cancers) in 1995 and 1996. Results: After adjusting for confounders, HRT users were more likely to have a false-negative screen [first round: odds ratio (OR), 1.99; 95% confidence interval (95% CI), 1.4-2.9; subsequent round: OR, 2.29; 95% CI, 1.4-3.8]. This effect was modestly attenuated by adjusting for mammographic density (first round: OR, 1.54; 95% CI, 1.0-2.3; subsequent round: OR, 1.97; 95% CI, 1.2-3.3). Adjusting for tumor characteristics resulted in a modest increase in the odds of a false negative at first round but had no effect at subsequent round. Conclusions: Mammographic density only partly explains the effect of HRT on sensitivity. Further research needs to clarify whether hyperemic breast tissue changes affect cancer detectability in HRT users as well as the possibility that the quality of mammography may be poor in some HRT users.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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