| 1. |
- Holm, Johanna, et al.
(författare)
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Risk factors and tumor characteristics of interval cancers by mammographic density
- 2015
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Ingår i: Journal of Clinical Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0732-183X. ; 33:9, s. 1030-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account. Patients and Methods: Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen- detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density. Results: Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m2 (OR, 0.49; 95% CI, 0.29 to 0.82). Conclusion: Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.
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| 2. |
- Li, Jingmei, et al.
(författare)
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Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers
- 2015
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Ingår i: Annals of Oncology. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0923-7534. ; 26:3, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. Patients and methods: A 77-SNP polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen-receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. Results: PRS weighted by breast cancer overall estimates was found to be differentially associated with 1,865 screen-detected and 782 interval cancers in the LIBRO-1 study (age-adjusted ORperSD [95% confidence interval]=0.91 [0.83-0.99], p=0.023). The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates (ORperSD=0.90 [0.82-0.98], p=0.011). This result was corroborated by two independent studies (combined ORperSD=0.87 [0.76-1.00], p=0.058) with no evidence of heterogeneity. When enriched for “true” interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced (ORperSD=0.74 [0.62-0.89], p=0.001), with a significant interaction effect between PRS and mammographic density (pinteraction=0.017). Conclusion: To our knowledge, this is the first report looking into the genetic differences between screendetected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.
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| 3. |
- Mavaddat, Nasim, et al.
(författare)
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Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 107:5, s. 036-036
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.
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