Comparison of the association of mammographic density and clinical factors with ductal carcinoma in situ versus invasive ductal breast cancer in Korean women.

BACKGROUND: In spite of the increasing incidence of in situ breast cancer, the information about the risk factors of in situ breast cancer (DCIS) is scarce as compared to the information available for invasive ductal breast cancer (IDC), with inconsistent findings regarding the difference in risk factors between DCIS and IDC. METHODS: We enrolled 472 women with IDC and 90 women with DCIS and 1088 controls matching for age and menopausal status. Information on risk factors was collected through self-administered questionnaire. Percent mammographic dense area (PDA), absolute mammographic dense area (ADA), and nondense area were assessed using a computer-assisted thresholding technique. Odds ratio (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression model with adjustment for covariates. RESULTS: Later age at menarche and regular physical exercise were associated with decreased risk of IDC, whereas alcohol consumption, previous benign breast disease, and family history of breast cancer were associated with increased risk of IDC. For DCIS, previous benign breast disease and alcohol consumption were associated with the increased risk, and regular physical exercise was associated with decreased risk. Increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.10 (95% CI: 1.01, 1.21) and 1.10 (95% CI: 1.01, 1.19) times greater risk of IDC, respectively. The increase of ADA by 1-quartile level and PDA increase by 10% were associated with 1.17 (95% CI: 0.91, 1.50) times and 1.11 (95% CI:0.90,1.37) times greater risk of DCIS, respectively, but the associations were not statistically significant. There was no significant difference in the association with risk factors and mammographic density measures between IDC and DCIS (P > 0.1). CONCLUSIONS: Differential associations of DCIS with mammographic density and risk factors as compared with the associations of IDC were not evident. This finding suggests that IDC and DCIS develop through the shared causal pathways.

Mammographic density defined by higher than conventional brightness threshold better predicts breast cancer risk for full-field digital mammograms.

INTRODUCTION: When measured using the computer-assisted method CUMULUS, mammographic density adjusted for age and body mass index predicts breast cancer risk. We asked if new mammographic density measures defined by higher brightness thresholds gave better risk predictions. METHODS: The Korean Breast Cancer Study included 213 women diagnosed with invasive breast cancer and 630 controls matched for age at full-field digital mammogram and menopausal status. Mammographic density was measured using CUMULUS at the conventional threshold (Cumulus), and in effect at two increasingly higher thresholds, which we call Altocumulus and Cirrocumulus, respectively. All measures were Box-Cox transformed and adjusted for age, body mass index, menopausal status and machine. We used conditional logistic regression to estimate the change in Odds PER standard deviation of transformed and Adjusted density measures (OPERA). The area under the receiver operating characteristic curve (AUC) was estimated. RESULTS: Corresponding Altocumulus and Cirrocumulus density measures were correlated with Cumulus measures (r approximately 0.8 and 0.6, respectively). Altocumulus and Cirrocumulus measures were on average 25% and 80% less, respectively, than the Cumulus measure. For dense area, the OPERA was 1.18 (95% confidence interval: 1.01-1.39, P = 0.03) for Cumulus; 1.36 (1.15-1.62, P < 0.001) for Altocumulus; and 1.23 (1.04-1.45, P = 0.01) for Cirrocumulus. After fitting the Altocumulus measure, the Cumulus measure was no longer associated with risk. After fitting the Cumulus measure, the Altocumulus measure was still associated with risk (P = 0.001). The AUCs for dense area was 0.59 for the Altocumulus measure, greater than 0.55 and 0.57 for the Cumulus and Cirrocumulus measures, respectively (P = 0.001). Similar results were found for percentage dense area measures. CONCLUSIONS: Altocumulus measures perform better than Cumulus measures in predicting breast cancer risk, and Cumulus measures are confounded by Altocumulus measures. The mammographically bright regions might be more aetiologically important for breast cancer, with implications for biological, molecular, genetic and epidemiological research and clinical translation.

Prognostic value of metabolic tumor volume and total lesion glycolysis in breast cancer: a meta-analysis.

OBJECTIVES: PET using F-fluorodeoxyglucose (FDG) has proven to be valuable in staging and monitoring of treatment response in breast cancer. We aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with breast cancer. METHODS: A systematic search of MEDLINE and EMBASE was performed using the keywords of breast cancer, PET, and volume. Inclusion criteria were F-FDG PET used as an initial imaging tool; studies limited to patients with breast cancer who had not undergone any treatment before PET scans; and studies reporting survival data. Event-free survival (EFS) and overall survival (OS) were considered markers of outcome. RESULTS: Nine studies comprising 975 patients were included in this study. The pooled hazard ratio (HR) for adverse events was 33.73 (P < 0.00001; I = 0%) with MTV from primary tumor and 2.89 (P < 0.00001; I = 45%) with TLG from primary tumor, meaning that primary tumors with high volumetric parameters were associated with progression or recurrence. However, the combined HRs for EFS of MTV, and TLG, and those for OS of MTV from whole-body tumor were NS. The pooled HR for OS of TLG from whole-body tumor was 2.95 (P = 0.18; I = 71%). CONCLUSION: Volumetric parameters from F-FDG PET are significant prognostic factors for outcome in patients with breast cancer. Patients with a high MTV or TLG from primary tumor have a higher risk of adverse events. Patients with a high TLG from whole-body tumor have a higher risk of deaths.

Mammographic Density and Circulating Sex Hormones: a Cross-Sectional Study in Postmenopausal Korean Women.

Mammographic density (MD) is a strong independent risk factor for breast cancer. It has been suggested that breast cancer is related to the exposure to circulating sex hormones. However, relations between MD and hormones have been inconsistent. In addition, such relations are mainly evaluated in Western populations. Therefore, we conducted a cross-sectional study in 396 cancer-free postmenopausal Korean women who had never used hormone replacement therapy. We assayed estradiol, testosterone, and sex hormone-binding globulin (SHBG) levels. We then calculated free testosterone (cFT) levels. Total and dense areas of digital mammogram were measured using a computer-assisted thresholding method, and non-dense area and percent dense area were calculated. Linear mixed model was used for analyses. Estradiol and testosterone levels were not associated with any MD measures after adjusting for reproductive factors and body mass index. However, cFT was persistently associated with non-dense area even after adjusting for covariates, with non-dense area increased by 3.5% per 1 standard deviation increase of cFT. SHBG showed an inverse association with non-dense area, although it showed a positive association with dense area and percent dense area regardless of adjustment for covariates. Non-dense area was decreased by 5.6% while percent dense area was increased by 13.4% per 1 standard deviation increase of SHBG. These findings suggest that SHBG might be related with breast cancer risk, probably through its association with breast density.

Association between mammographic density and tumor marker-defined breast cancer subtypes: a case-control study.

High mammographic density (MD) is the most important risk factor for breast cancer. This study aimed to clarify the relationship between MD and breast cancer subtypes defined by tumor markers. We enrolled 642 women with breast cancer (69% premenopausal) and 1241 controls matched for age and menopausal status. Absolute mammographic dense area (ADA), percent mammographic dense area (PDA), and nondense area were assessed using a computer-assisted thresholding technique. We classified breast cancer cases into four subtypes using information on tumor marker expression such as estrogen receptor (ER), progesterone receptor (PR), and Cerb2 receptor (HER2); luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2-overexpressing (ER-, PR-, and HER2+), and triple-negative (ER-, PR-, and HER2-). Analysis was carried out using a conditional logistic regression model with adjustment for covariates. ADA and PDA were associated positively with the risk of breast cancer overall. Both ADA and PDA tended to have a positive association with breast cancer with any ER, any PR, or HER2-, but not for HER2+. The risk of luminal A breast cancer increased significantly 1.11 times (95% confidence interval: 1.01-1.23) for ADA and 1.12 times (95% confidence interval: 1.01-1.24) for PDA, estimated per 1 SD of the age and BMI-adjusted MD. However, the risk of breast cancer with luminal B, HER2-overexpressing, and triple-negative subtypes did not differ (P>0.10). Differential associations between MD measures and breast cancer by tumor marker status or tumor marker-defined subtypes were not detected. These findings suggested that the association between MD and breast cancer subtype may be because of other causal pathways.