Efficacy of MRI and Mammography for Breast-Cancer Screening in Women with a Familial or Genetic Predisposition

Leiden University, Leyden, South Holland, Netherlands
New England Journal of Medicine (Impact Factor: 55.87). 07/2004; 351(5):427-37. DOI: 10.1056/NEJMoa031759
Source: PubMed


The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women.
Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups.
We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups.
MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.

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Available from: Rob A E M Tollenaar, Oct 13, 2015
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    • "A large proportion of BRCA1/2-associated breast cancers detected during adequate surveillance (including breast MRI) is smaller than 1.0 cm (pT1) and node negative [10]. Potentially, routine assessment of tumor-associated inflammation may help improve risk stratification of these early BRCA1/2-associated breast cancers to further personalize (adjuvant) treatment. "
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    ABSTRACT: The prognosis of BRCA1/2-associated breast cancer partly depends on histologic characteristics. Most of these breast cancers, however, are poorly differentiated. BRCA1-associated cancers are mainly negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Consequently, the use of these histologic features for risk stratification in BRCA1/2 breast cancer is limited. We assessed the prognostic value of additional histologic features, including tumor-associated inflammation and tumor-associated stroma in BRCA1/2 breast cancer patients. From the Rotterdam Family Cancer Clinic database, we collected demographics, tumor characteristics, and follow-up data from female BRCA1/2 breast cancer patients. Tumor samples were centrally reviewed including histologic subtype, differentiation grade, tumor-associated inflammation density, amount of tumor-associated stroma, and intratumor necrosis. The impact of these factors on recurrence-free survival (RFS) was evaluated using univariate and multivariate Cox regression, adjusted for established prognostic features and year of diagnosis. We included 138 BRCA1 and 37 BRCA2 breast cancer patients. Median follow-up after diagnosis was 9.7 years. Independent prognostic factors for RFS were tumor size (hazard ratio [HR], 2.47 for >2 versus ≤2 cm; 95% confidence interval [95% CI], 1.10-5.57), tumor-associated inflammation (HR, 0.18 for moderate/marked versus absent/mild; 95% CI, 0.05-0.61), and intratumor necrosis (HR, 2.60 for presence versus absence; 95% CI, 1.12-6.05). Established prognostic factors as nodal status and differentiation grade were not significantly related to RFS. Subgroup analyses of 138 BRCA1 and 118 triple-negative breast cancer cases showed similar results. Tumor-associated inflammation density was the strongest predictor for RFS in this series of BRCA1/2 breast cancer patients. This provides a potential risk stratification tool that can easily be implemented in routine histologic examination. Copyright © 2014 Elsevier Inc. All rights reserved.
    Human pathology 11/2014; 46(2). DOI:10.1016/j.humpath.2014.10.020 · 2.77 Impact Factor
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    • "MRI is expensive and not widely available to all patients. Moreover, breast MRI suffers from low specificity, which leads to unnecessary biopsies (Kriege et al. 2004; Morris 2001). To overcome these limitations and to enhance the sensitivity and specificity of breast cancer imaging, researchers have examined the utility of new imaging techniques such as elastography (Garra et al. 1997; Plewes et al. 2000; Sharma et al. 2004; Tanter et al. 2008; Zhi et al. 2007), photo-acoustic imaging (Manohar et al. 2005) and diffuse optical tomography (Ntziachristos and Chance 2000). "
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    ABSTRACT: We previously investigated the application of a novel imaging modality, vibro-acoustography (VA), using an annular confocal transducer (confocal VA) integrated into a clinical prone stereotactic mammography system, to detect various breast abnormalities. To shorten the scanning time and provide improved coverage of the breast, we have evolved our imaging system by implementing VA on a clinical ultrasound scanner equipped with a “quasi-2-D” array transducer. We call this technique “quasi-2-D vibro-acoustography” (Q2-DVA). A clinical ultrasound scanner (GE Vivid 7) was modified to perform both ultrasound imaging and VA using an array transducer consisting of a matrix of 12 rows by 70 columns of ultrasound elements. The newly designed system was used to perform VA on patients with either benign or cancerous lesions. Our results indicate that benign and malignant solid breast lesions were easily detected using our newly modified VA system. It was also possible to detect microcalcifications within the breast. Our results suggest that with further development, Q2-DVA could provide high-resolution diagnostic information in the clinical setting and may be used either as a stand-alone or as a complementary tool in support of other clinical imaging modalities.
    Ultrasound in Medicine & Biology 08/2014; 40(12). DOI:10.1016/j.ultrasmedbio.2014.07.005 · 2.21 Impact Factor
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    • "Breast cancer is the third most common form of cancer, with almost 1.5 million women in the world diagnosed with the disease in 2010 alone [1,2]. The extensive use of mammography has resulted in a large proportion of breast cancer cases being detected at an earlier stage, resulting in increased survival and outcome [3]. However, approximately 3-6% of patients continue to present with metastatic disease at diagnosis throughout the US and Europe [4,5]. "
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    ABSTRACT: Background A germline, variant in the BRCA1 3’UTR (rs8176318) was previously shown to predict breast and ovarian cancer risk in women from high-risk families, as well as increased risk of triple negative breast cancer. Here, we tested the hypothesis that this variant predicts tumor biology, like other 3’UTR mutations in cancer. Methods The impact of the BRCA1-3’UTR-variant on BRCA1 gene expression, and altered response to external stimuli was tested in vitro using a luciferase reporter assay. Gene expression was further tested in vivo by immunoflourescence staining on breast tumor tissue, comparing triple negative patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3’UTR. To determine the significance of the variant on clinically relevant endpoints, a comprehensive collection of West-Irish breast cancer patients were tested for the variant. Finally, an association of the variant with breast screening clinical phenotypes was evaluated using a cohort of women from the High Risk Breast Program at the University of Vermont. Results Luciferase reporters with the BRCA1-3’UTR-variant (T allele) displayed significantly lower gene expression, as well as altered response to external hormonal stimuli, compared to the non-variant 3’UTR (G allele) in breast cancer cell lines. This was confirmed clinically by the finding of reduced BRCA1 gene expression in triple negative samples from patients carrying the homozygous TT variant, compared to non-variant patients. The BRCA1-3’UTR-variant (TG or TT) also associated with a modest increased risk for developing breast cancer in the West-Irish cohort (OR = 1.4, 95% CI 1.1-1.8, p = 0.033). More importantly, patients with the BRCA1-3’UTR-variant had a 4-fold increased risk of presenting with Stage IV disease (p = 0.018, OR = 3.37, 95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not difficulty screening, obese women with the BRCA1-3’UTR-variant had significantly less dense breasts (p = 0.0398) in the Vermont cohort. Conclusion A variant in the 3’UTR of BRCA1 is functional, leading to decreased BRCA1 expression, modest increased breast cancer risk, and most importantly, presentation with stage IV breast cancer, likely due to aggressive tumor biology.
    BMC Cancer 06/2014; 14(1):421. DOI:10.1186/1471-2407-14-421 · 3.36 Impact Factor
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