Ductal Carcinoma In Situ: Risk Factors and Impact of Screening

Division of Health Policy and Management, School of Public Health, University of Minnesota, A365 Mayo (MMC 729), 420 Delaware St SE, Minneapolis, MN 55455, USA.
JNCI Monographs 10/2010; 2010(41):113-6. DOI: 10.1093/jncimonographs/lgq024
Source: PubMed


The National Institutes of Health Office of Medical Applications of Research commissioned a structured literature review on the incidence of ductal carcinoma in situ (DCIS) as a background paper for the State of the Science Conference on Diagnosis and Management of DCIS.
Published studies were abstracted from MEDLINE and other sources. We include articles published through January 31, 2009; 92 publications were abstracted.
DCIS incidence rose from 1.87 per 100,000 in 1973-1975 to 32.5 per 100,000 in 2005. Increases in incidence were greatest in tumors without comedo necrosis. Incidence increased in all ages but more in women older than 50 years. Increased use of mammography explains some but not all of the increased incidence. Risk factors for incident DCIS include older age and positive family history. Whereas tamoxifen prevents both invasive breast cancer and DCIS, raloxifene is associated with decreased invasive breast cancer but not decreased DCIS.
Scientific questions deserving further investigation include the relationship between mammography use and DCIS incidence and the role of chemoprevention for reducing the incidence of DCIS and invasive breast cancer.

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    • "A long-term follow-up study [30] found that the rate of local recurrence was high, and 48% of these recurrences were invasive. Previous studies [21-25] suggest that family history is a risk factor of DCIS. However, no relationship between family history and risk of DCIS was observed in Han Chinese people. "
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    ABSTRACT: The association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population. A case--control study, comprising 926 breast cancer patients and 1,187 benign breast disease controls, was conducted in our hospital. Multivariate logistic regression was used to assess the relationships between family history and risk of DCIS or triple negative breast cancer. Subjects with a family history of breast cancer had higher breast cancer risk than those without a family history (odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.26 to 3.52). Family history was not significantly associated with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family history was significantly associated with an increased risk of invasive breast cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer (OR = 2.14, 95% CI = 1.21 to 3.80). Our results indicate that having a family history of breast cancer is associated with an increased risk of triple negative breast cancer with a magnitude of association similar to that for non-triple negative breast cancer. Furthermore, family history is not significantly associated with an increased risk of DCIS. Future cohort studies with larger sample sizes are still needed to explore these relationships.
    World Journal of Surgical Oncology 10/2013; 11(1):248. DOI:10.1186/1477-7819-11-248 · 1.41 Impact Factor
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    • "Re-operation is itself associated with further increased risk of subsequent local recurrence [4]. In addition to the problem of identifying additional therapeutic targets in these recurrent cases of DCIS, there is also the issue of over-treatment in the majority of DCIS cases that would remain indolent in the absence of surgery and radiation [5], [6]. Another challenge that DCIS presents is the heterogeneity of the lesions [7], [8]. "
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    ABSTRACT: Breast ductal carcinoma in situ (DCIS) is being found in great numbers of women due to the widespread use of mammography. To increase knowledge of DCIS, we determined the expression changes that are common among three DCIS models (MCF10.DCIS, SUM102 and SUM225) compared to the MCF10A model of non-tumorigenic mammary epithelial cells in three dimensional (3D) overlay culture with reconstituted basement membrane (rBM). Extracted mRNA was subjected to 76 cycles of deep sequencing (RNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of RNA-Seq results showed 295 consistently differentially expressed transcripts in the DCIS models. These differentially expressed genes encode proteins that are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFβ signaling, show association with cell-cell signaling, cell-cell adhesion and cell proliferation, and have a notable bias toward localization in the extracellular and plasma membrane compartments. RNA-Seq data was validated by quantitative real-time PCR of selected differentially expressed genes. Aldehyde dehydrogenase 5A1 (ALDH5A1) which is an enzyme that is involved in mitochondrial glutamate metabolism, was over-expressed in all three DCIS models at both the mRNA and protein levels. Disulfiram and valproic acid are known to inhibit ALDH5A1 and are safe for chronic use in humans for other disorders. Both of these drugs significantly inhibited net proliferation of the DCIS 3D rBM overlay models, but had minimal effect on MCF10A 3D rBM overlay models. These results suggest that ALDH5A1 may play an important role in DCIS and potentially serve as a novel molecular therapeutic target.
    PLoS ONE 12/2012; 7(12):e50249. DOI:10.1371/journal.pone.0050249 · 3.23 Impact Factor
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    ABSTRACT: While ductal carcinoma in situ (DCIS) is seldom life threatening, the management of DCIS remains a dilemma for patients and their physicians. Aggressive treatment reduces the risk of ipsilateral breast tumor recurrence (IBTR), but has never been proven to improve survival. There is interest in identifying the prognostic factors for determining low-risk DCIS patients, but a comprehensive review of high-quality evidence on tumor characteristics in predicting local recurrence has never been carried out. We examined the following tumor characteristics: biomarkers, comedonecrosis, focality, surgical margin, method of detection, tumor grade, and tumor size. For this systematic review we restricted the analyses to the results of subgroup analyses from randomized controlled trials (RCTs) and multivariate analyses from RCTs and observational studies. We identified 44 eligible articles. The pooled random-effects risk estimates for IBTR are comedonecrosis 1.71(95% CI, 1.36-2.16), focality 1.95(95% CI, 1.59-2.40), margin 2.25(95% CI, 1.77-2.86), method of detection 1.35(95% CI, 1.12-1.62), tumor grade 1.81(95% CI, 1.53-2.13), and tumor size 1.63(95% CI, 1.30-2.06). Limited evidence indicated that women whose DCIS is ER-negative, PR-negative, or HER2/neu receptor positive have an IBTR higher than those whose DCIS is ER-positive, PR-positive, and HER2/neu receptor negative. A variety of tumor characteristics are significant predictors for IBTR. These results are important for both clinicians and patients to interpret the risk of local recurrence and to decide on a course of treatment.
    Breast Cancer Research and Treatment 02/2011; 127(1):1-14. DOI:10.1007/s10549-011-1387-4 · 3.94 Impact Factor
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