Association between Breast Density and Subsequent Breast Cancer Following Treatment for Ductal Carcinoma In situ

Department of Surgery, University of California, San Francisco Cancer Center, 1600 Divisadero Avenue, B606 San Francisco, CA 94115, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 01/2008; 16(12):2587-93. DOI: 10.1158/1055-9965.EPI-07-0458
Source: PubMed


Risk of invasive cancer following treatment for ductal carcinoma in situ (DCIS) is associated with both treatment- and tumor-related factors. However, it is unknown whether stromal factors such as breast density may also influence subsequent invasive breast events. We investigated whether breast density is an independent predictor of subsequent breast events among women treated for DCIS. Population: A prospective cohort study of 3,274 women ages 30 to 93 in the Breast Cancer Surveillance Consortium treated with lumpectomy for DCIS between 1993 and 2005. All subjects had an American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density measure recorded prior to diagnosis.
Ipsilateral and contralateral breast cancer following lumpectomy for DCIS were ascertained through state tumor registries, regional Surveillance Epidemiology and End Results program or pathology databases. A Cox proportional hazard model was used to compare adjusted risk of breast cancer among women with high (BI-RADS 3 or 4) versus low (BI-RADS 1 or 2) breast density.
During a median follow-up period of 39 months (0-132 months), 133 women developed invasive breast cancer. After adjusting for age and radiation treatment, high breast density was associated with increased hazard for contralateral (hazard ratio, 3.1; 95% confidence interval, 1.6-6.1) but not ipsilateral (hazard ratio, 1.0; 95% confidence interval, 0.6-1.6) invasive breast events.
High breast density is associated with contralateral, but not ipsilateral, invasive breast cancer following lumpectomy for DCIS. Thus, women with DCIS and high breast density may especially benefit from antiestrogenic therapy to reduce the risk of contralateral invasive disease.

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    • "Studies that have examined risk of a second invasive or in situ breast cancer are summarized in Table 4. Four [79,90-92] of the five [79,90-93] studies show an increased risk of a second cancer in the ipsilateral breast, and three [90,91,93] of the five show an increased risk in the contralateral breast. Only one [79] of the three [79,91,93] studies to examine the potential modifying role of radiation therapy found evidence that risk of a second breast cancer was higher in those who did not receive radiation. "
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    ABSTRACT: Variations in percent mammographic density (PMD) reflect variations in the amounts of collagen and number of epithelial and non-epithelial cells in the breast. Extensive PMD is associated with a markedly increased risk of invasive breast cancer. The PMD phenotype is important in the context of breast cancer prevention because extensive PMD is common in the population, is strongly associated with risk of the disease, and, unlike most breast cancer risk factors, can be changed. Work now in progress makes it likely that measurement of PMD will be improved in the near future and that understanding of the genetics and biological basis of the association of PMD with breast cancer risk will also improve. Future prospects for the application of PMD include mammographic screening, risk prediction in individuals, breast cancer prevention research, and clinical decision making.
    Full-text · Article · Nov 2011 · Breast cancer research: BCR
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    ABSTRACT: Whether measured by qualitative assessment of the parenchyma pattern or quantitatively by percent mammographic density, breast density is consistently a strong and independent risk factor for breast cancer (BC). Density is also a relatively common risk factor, and therefore an important contributor to BC risk at a population level. Including density (with other risk factors) in risk prediction models improves predictive accuracy; however, better standardization and/or automation of density measures will make the integration of breast density into risk assessment, and its application in tailored screening and primary prevention, more feasible. High breast density reduces screening sensitivity and is associated with risk of interval BC in screening; it is also associated with cancers that have poorer prognostic features. Non-randomized studies of adjunct ultrasound screening in women with mammography-negative dense breasts have provided evidence on incremental detection of BC with adjunct ultrasound and high false-positives but have not examined impact on clinical end-points, mortality, or balance of potential benefits versus harms.
    No preview · Article · Jun 2012 · Current Breast Cancer Reports
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    ABSTRACT: Women with ductal carcinoma in situ (DCIS) are at substantially increased risk for a second breast cancer, but few strong predictors for these subsequent tumors have been identified. We used Cox regression modeling to examine the association between mammographic density at diagnosis of DCIS of 504 women from the National Surgical Adjuvant Breast and Bowel Project B-17 trial and risk of subsequent breast cancer events. In this group of patients, mostly 50 years old or older, approximately 6.6% had breasts categorized as highly dense (i.e., ≥75% of the breast occupied by dense tissue). After adjusting for treatment with radiotherapy, age, and body mass index, women with highly dense breasts had 2.8 (95% confidence interval [CI] = 1.3 to 6.1) times the risk of subsequent breast cancer (DCIS or invasive), 3.2 (95% CI = 1.2 to 8.5) times the risk of invasive breast cancer, and 3.0 (95% CI = 1.2 to 7.5) times the risk of any ipsilateral breast cancer, compared with women with less than 25% of the breast occupied by dense tissue. Our results provide initial evidence that the risk of second breast cancers may be increased among DCIS patients with highly dense breasts.
    Preview · Article · Oct 2004 · Journal of the National Cancer Institute
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