| 1. |
- Azam, Shadi
(författare)
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Determinants and influence of mammographic features on breast cancer risk
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mammographic density and mammographic microcalcifications are the key imaging features in mammography examination. Mammographic density is known as a strong risk factor for breast cancer and is the radiographic appearance of epithelial and fibrous tissue which appears white on a mammogram. While, the dark part of a mammogram represents the fatty tissue. Mammographic microcalcifications appear as small deposits of calcium and they are one of the earliest sign of breast cancer. Malignant microcalcifications are seen in both in situ and invasive lesions. In this thesis we used the data from the prospective KARMA cohort to study the association between established breast cancer risk factors with mammographic density change over time (Study I), to examine the association between annual mammographic density change and risk of breast cancer (Study II), to investigate the association between established risk factors for breast cancer and microcalcification clusters and their asymmetry (Study III), and finally to elucidate the association between microcalcification clusters, their asymmetry, and risk of overall and subtype specific breast cancer (Study IV). The lifestyle and reproductive factors were assessed using web-based questionnaires. Average mammographic density and total microcalcification clusters were measured using a Computer Aided Detection system (CAD) and the STRATUS method, respectively. In Study I, the average yearly dense area change was -1.0 cm . Body mass index (BMI) and physical activity were statistically associated with density change. Beside age, lean and physically active women had the largest decrease in mammographic density per year. In Study II, overall, 563 women were diagnosed with breast cancer and annual mammographic density change did not seem to influence the risk of breast cancer. Furthermore, density change does not seem to modify the association between baseline density and risk of breast cancer. In Study III, age, mammographic density, genetic factors related to breast cancer, having more children, longer duration of breast-feeding were significantly associated with increased risk of presence of microcalcification clusters. In Study IV, 676 women were diagnosed with breast cancer. Further, women with 33 microcalcification clusters had 2 times higher risk of breast cancer compared to women with no clusters. Microcalcification clusters were associated with both in situ and invasive breast cancer. Finally, during postmenopausal period, microcalcification clusters influence risk of breast cancer to the similar extend as baseline mammographic density. In conclusion, we have identified novel determinants of mammographic density changes and potential predictors of suspicious mammographic microcalcification clusters. Further, our results suggested that annual mammographic density change does not influence breast cancer risk, while presence of suspicious microcalcification clusters was strongly associated with breast cancer risk.
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| 2. |
- Gabrielson, Marike, et al.
(författare)
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Hormonal determinants of mammographic density and density change
- 2020
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Ingår i: Breast Cancer Research. - : BMC. - 1465-5411 .- 1465-542X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm(2)) and annual MD change (cm(2)/year). Methods This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n = 2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. Results Greater baseline mean MD was associated with overall higher concentrations of progesterone (average + 1.29 cm(2)per doubling of hormone concentration), 17OH-progesterone (+ 1.09 cm(2)), oesterone sulphate (+ 1.42 cm(2)), prolactin (+ 2.11 cm(2)) and SHBG (+ 4.18 cm(2)), and inversely associated with 11-deoxycortisol (- 1.33 cm(2)). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was - 0.8 cm(2). Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was - 0.96 cm(2)and - 1.16 cm(2)lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. Conclusions Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.
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| 3. |
- Holowko, Natalie, et al.
(författare)
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Heritability of mammographic breast density, density change, microcalcifications, and masses
- 2020
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Ingår i: Cancer Research. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0008-5472. ; 80:7, s. 1590-1600
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important since the mechanisms through which they are associated with breast cancer are not well known. Methods: Mammographic screening history and detailed questionnaire data for 56,820 women from the KARMA prospective cohort study were used. The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC – cm2/year) were estimated using 1,940 sister pairs. We investigated the association between a genetic predisposition to breast cancer and mammographic features, among women with family history of breast cancer information (N=49,674) and a polygenic risk score (PRS, N=9,365). Results: Heritability was estimated at 58% (95% CI: 48%, 67%) for MD, 23% (2%, 45%) for microcalcifications, and 13% (1%, 25%) for masses. The estimated heritability for MDC was essentially null (2%, 95% CI: -8%, 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction. Conclusions: We confirmed previous findings of heritability in MD, and also found heritability of the number of microcalcifications and masses at baseline. Since these features are associated with breast cancer risk, and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer.
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