Interpretation of Digital Mammograms: Comparison of Speed and Accuracy of Soft-Copy versus Printed-Film Display

PURPOSE: To compare the speed and accuracy of the interpretations of digital mammograms by radiologists by using printed-film versus soft-copy display. MATERIALS AND METHODS: After being trained in interpretation of digital mammograms, eight radiologists interpreted 63 digital mammograms, all with old studies for comparison. All studies were interpreted by all readers in soft-copy and printed-film display, with interpretations of images in the same cases at least 1 month apart. Mammograms were interpreted in cases that included six biopsy-proved cancers and 20 biopsy-proved benign lesions, 20 cases of probably benign findings in patients who underwent 6-month follow-up, and 17 cases without apparent findings. Area under the receiver operating characteristic curve (Az), sensitivity, and specificity were calculated for soft-copy and printed-film display. RESULTS: There was no significant difference in the speed of interpretation, but interpretations with soft-copy display were slightly faster. The differences in Az, sensitivity, and specificity were not significantly different; Az and sensitivity were slightly better for interpretations with printed film, and specificity was slightly better for interpretations with soft copy. CONCLUSION: Interpretation with soft-copy display is likely to be useful with digital mammography and is unlikely to significantly change accuracy or speed

Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer

Polymorphisms in the cytochrome P450 1B1 (CYP1B1) and glutathione S-transferase (GST) drug metabolic enzymes, which are responsible for metabolic activation/detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one CYP1B1 119S allele (OR=0.53; 95% CI=0.20–1.40) and increased risk for those women harboring at least one CYP1B1 432V allele (OR=5.52; 95% CI=0.50–61.37). Stratified analyses demonstrated significant interactions in younger (age ≤60) Caucasian women with the CYP1B1 119SS genotype (OR=3.09; 95% CI=1.22–7.84) and younger African-American women with the GSTT1 null genotype (OR=4.07; 95% CI=1.12–14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at GSTP1 114 (OR=2.12; 95% CI=1.02–4.41). In Caucasian women, the combined GSTP1 105IV/VV and CYP1B1 119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04–3.72) and the three way combination of GSTP1 105IV/VV, CYP1B1 119AS/SS and GSTT1 null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27–12.40). These results suggest the importance of estrogen/carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation

Abstract 2613: Racial/Ethnic specific polygenic models of breast cancer risk

Abstract Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Earlier family linkage studies have identified high-penetrance breast cancer genes, such as BRCA1, BRCA2, and TP53. Moreover, genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, have been associated with moderate breast cancer risk. Recent Genome-wide Association Studies (GWAS) have identified multiple single nucleotide polymorphisms (SNPs) associated with breast cancer risk. We evaluated whether breast cancer risk is associated with multiple SNPs in DNA damage signaling and repair and immune and inflammatory responses in addition to SNPs identified from GWAS. We hypothesize that targeting critical candidate pathways may yield important information regarding SNP-SNP interactions in breast cancer risk. We selected SNPs from DNA damage signaling and cell cycle control, base excision repair, nucleotide excision repair, double-strand break repair, mismatch repair, and immune and inflammatory responses. We have genotype results of 3,754 SNPs in 910 controls (763 Whites and 147 African Americans) and 793 breast cancer cases (667 Whites and 116 African Americans). 16.2% and 20.6% of controls and cases (respectively) had a first degree relative with breast cancer. 48% and 55.7% of the controls and cases (respectively) had their first child before or at the age of 24. 40.5% and 42.2% of the controls and cases (respectively) had a history of smoking. Our study results suggest that 6 SNPs were associated with breast cancer risk in Whites: (1) 2 SNPs from GWAS - rs3817198 in LSP1 (p&amp;lt;0.001) and rs3803662 in TNRC9 (p&amp;lt;0.001); (2) 2 SNPs from inflammation - rs1801157 in SDF-1 (p&amp;lt;0.001) and rs12720356 in Tyk2 (p&amp;lt;0.001) and (3) 2 SNPs from DNA repair and apoptosis - rs2992 in CHAF1A (p&amp;lt;0.0001) and rs2231301 in BCL2l2 (p&amp;lt;0.001). Only 1 SNP, rs1990760 in IFIH1 (p&amp;lt;0.01) was associated with breast cancer risk in African Americans. The IFIH1 gene was previously linked to Type 1 diabetes but not in cancer risk. There was significant trend in breast cancer risk with increasing numbers of risk genotypes for rs3817198, rs3803662, rs1801157, rs12720356, rs2992, and rs2231301 (p test for trend &amp;lt;0.0001) in Whites after adjustment for potential confounders. Our results suggest that multiple SNPs contribute to breast cancer risk in a racial/ethnic specific manner and larger studies are warranted to further evaluate our findings. More importantly, functional analysis is under way to corroborate the association of multiple SNPs with breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2613. doi:1538-7445.AM2012-2613</jats:p

Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk

Genetic variations in DNA repair may impact repair functions, DNA damage and breast cancer risk. Using data/samples collected from the first 752 Caucasians and 141 African-Americans in an ongoing case-control study, we examined the association between breast cancer risk and 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways-(i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) double-strand break repair: NBS1 E185Q and XRCC3 T241M. In Caucasians, breast cancer risk was significantly associated with ADPRT 762VV [odds ratio (OR) = 1.45; 95% confidence interval (CI) = 1.03, 2.03], APE1 148DD (OR = 1.44; 95% CI = 1.03, 2.00), MLH1 219II/IV (OR = 1.87; 95% CI = 1.11, 3.16) and ERCC4 415QQ (OR = 8.64; 95% CI = 1.04, 72.02) genotypes. With a limited sample size, we did not observe any significant association in African-Americans. However, there were significant trends in breast cancer risk with increasing numbers of risk genotypes for ADPRT 762VV, APE1 148DD, ERCC4 415RQ/QQ and MLH1 219II/IV (P trend < 0.001) in Caucasians and ADPRT 762VA, ERCC2 751KQ/QQ and NBS1 185EQ/QQ in African-Americans (P trend = 0.006), respectively. Our results suggest that combined nsSNPs in multiple DNA repair pathways may contribute to breast cancer risk and larger studies are warranted to further evaluate polygenic models of DNA repair in breast cancer risk