An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain

Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk. Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic. Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories. Conclusions: These models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.This study was funded by grant PS09/01340 and The Spanish Network on Chronic Diseases REDISSEC (RD12/0001/0007) from the Health Research Fund (Fondo de Investigación Sanitaria) of the Spanish Ministry of Health

Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms

We developed a semi-automated tool to assess mammographic density (MD), a phenotype risk marker for breast cancer (BC), in full-field digital images and evaluated its performance testing its reproducibility, comparing our MD estimates with those obtained by visual inspection and using Cumulus, verifying their association with factors that influence MD, and studying the association between MD measures and subsequent BC risk. Three radiologists assessed MD using DM-Scan, the new tool, on 655 processed images (craniocaudal view) obtained in two screening centers. Reproducibility was explored computing pair-wise concordance correlation coefficients (CCC). The agreement between DM-Scan estimates and visual assessment (semi- uantitative scale, 6 categories) was quantified computing weighted kappa statistics (quadratic weights). DM-Scan and Cumulus readings were compared using CCC. Variation of DM-Scan measures by age, body mass index (BMI) and other MD modifiers was tested in regression mixed models with mammographic device as a random-effect term. The association between DM-Scan measures and subsequent BC was estimated in a case control study. All BC cases in screening attendants (2007 2010) at a center with full-field digital mammography were matched by age and screening year with healthy controls (127 pairs). DM-Scan was used to blindly assess MD in available mammograms (112 cases/119 controls). Unconditional logistic models were fitted, including age, menopausal status and BMI as confounders. DM-Scan estimates were very reliable (pairwise CCC: 0.921, 0.928 and 0.916). They showed a reasonable agreement with visual MD assessment (weighted kappa ranging 0.79-0.81). DM-Scan and Cumulus measures were highly concordant (CCC ranging 0.80-0.84), but ours tended to be higher (4%-5% on average). As expected, DM-Scan estimates varied with age, BMI, parity and family history of BC. Finally, DM-Scan measures were significantly associated with BC (p-trend=0.005). Taking MD=29%=3.10 (95% CI=1.35-7.14). Our results confirm that DM-Scan is a reliable tool to assess MD in full-field digital mammograms.This work was supported by research grants from Spain's Health Research Fund (Fondo de INvestigacion Santiaria) (PI060386 & PI09/1230); Gent per Gent Fund (EDEMAC Project) and the Spanish Federation of Breast Cancer Patients (Federacion Espanola de Cancer de Mama) (FECMA 485 EPY 1170-10).Pollán, M.; Llobet Azpitarte, R.; Miranda García, J.; Antón Guirao, J.; Casals El Busto, M.; Martinez Gomez, I.; Palop Jonquères, C.... (2013). Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms. 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Obstetric history and mammographic density: a population-based cross-sectional study in Spain (DDM-Spain)

High mammographic density (MD) is used as a phenotype risk marker for developing breast cancer. During pregnancy and lactation the breast attains full development, with a cellular-proliferation followed by a lobular-differentiation stage. This study investigates the influence of obstetric factors on MD among pre- and post-menopausal women. We enrolled 3,574 women aged 45–68 years who were participating in breast cancer screening programmes in seven screening centers. To measure MD, blind anonymous readings were taken by an experienced radiologist, using craniocaudal mammography and Boyd’s semiquantitative scale. Demographic and reproductive data were directly surveyed by purpose-trained staff at the date of screening. The association between MD and obstetric variables was quantified by ordinal logistic regression, with screening centre introduced as a random effect term. We adjusted for age, number of children and body mass index, and stratified by menopausal status. Parity was inversely associated with density, the probability of having high MD decreased by 16% for each new birth (P value < 0.001). Among parous women, a positive association was detected with duration of lactation [>9 months: odds ratio (OR) = 1.33; 95% confidence interval (CI) = 1.02–1.72] and weight of first child (>3,500 g: OR = 1.32; 95% CI = 1.12–1.54). Age at first birth showed a different effect in pre- and post-menopausal women (P value for interaction = 0.030). No association was found among pre-menopausal women. However, in post-menopausal women the probability of having high MD increased in women who had their first child after the age of 30 (OR = 1.53; 95% CI = 1.17–2.00). A higher risk associated with birth of twins was also mainly observed in post-menopausal women (OR = 2.02; 95% CI = 1.18–3.46). Our study shows a greater prevalence of high MD in mothers of advanced age at first birth, those who had twins, those who have breastfed for longer periods, and mothers whose first child had an elevated birth weight. These results suggest the influence of hormones and growth factors over the proliferative activity of the mammary gland

Survival, causes of death, and risk factors associated with mortality in Barcelona HIV new diagnoses. 2001-2013

The antiretroviral treatment has supposed a decrease in HIV-related mortality. We assessed factors related to survival in HIV individuals. Causes of death (CoD) in HIV individuals were described. Abstract methods Deaths registered in the Census until 30.06.2013 and 2001-2012 new diagnoses from Barcelona HIV Register were included in the analysis. The CoD were obtained from Death Register. The CoD were classified in external (ICD-10: X), HIV-related (B20-B24, B44.9, C83.7 and C85.9) and non-HIV-related (other codes) causes. Mortality rate was calculated as follow-up person-year per 1000 and its 95% confidence interval (M; 95%CI). Association with mortality of socio-demographic, clinical and epidemiological variables were studied using Cox regression [hazard ratio (HR); 95%CI]. Abstract results Among 3533 new HIV diagnoses, 168 (5%) died (M:8.2; 95%CI: 6.9-9.4). CoD was available in 93 (55%). Among those, 43% died by non-HIVrelated causes (M:1.9; 95%CI:1.3-2.5); 42% by HIV-related causes (M:1.9; 95%CI:1.3-2.5), and 15% by external ones (M:0.7; 95%CI:0.3-1.0). Worse survival was observed in injecting drug users (IDU)(HR:4.7; 95%CI:2.9-7.7) and heterosexual (HTS) men (HR:2.4; 95%CI:1.4-3.9), Spaniards (HR:2.5; 95%CI:1.6-4.0), Gràcia district residents (HR:2.0; 95%CI:1.1-3.7), illiterate/primary education individuals (HR:1.5; IC95%:1.1-2.2), and &lt;200 CD4 subjects (HR:1.8; 95%CI:1.2-3.0). HIV-related CoD were due to infections (48%): most common in men who have sex with men (MSM) (63%), followed by HTS women (60%). Non-HIV-related CoD were cancer (29%): more prevalent in men (32%), people with have secondary/university studies (39%) and HTS men (50%); cardiovascular diseases (22%): in HTS women (57%) and illiterate/primary education individuals (35%) and; liver diseases (19%): in IDU (37%). Abstract conclusion Mortality was associated with being IDU, HTS man, Spaniard, with low educational level and damaged immune system. CoD frequencies in HIVrelated and non-HIV-related were simila

Survival, causes of death, and risk factors associated with mortality in Barcelona HIV new diagnoses. 2001-2013

The antiretroviral treatment has supposed a decrease in HIV-related mortality. We assessed factors related to survival in HIV individuals. Causes of death (CoD) in HIV individuals were described. Abstract methods Deaths registered in the Census until 30.06.2013 and 2001-2012 new diagnoses from Barcelona HIV Register were included in the analysis. The CoD were obtained from Death Register. The CoD were classified in external (ICD-10: X), HIV-related (B20-B24, B44.9, C83.7 and C85.9) and non-HIV-related (other codes) causes. Mortality rate was calculated as follow-up person-year per 1000 and its 95% confidence interval (M; 95%CI). Association with mortality of socio-demographic, clinical and epidemiological variables were studied using Cox regression [hazard ratio (HR); 95%CI]. Abstract results Among 3533 new HIV diagnoses, 168 (5%) died (M:8.2; 95%CI: 6.9-9.4). CoD was available in 93 (55%). Among those, 43% died by non-HIVrelated causes (M:1.9; 95%CI:1.3-2.5); 42% by HIV-related causes (M:1.9; 95%CI:1.3-2.5), and 15% by external ones (M:0.7; 95%CI:0.3-1.0). Worse survival was observed in injecting drug users (IDU)(HR:4.7; 95%CI:2.9-7.7) and heterosexual (HTS) men (HR:2.4; 95%CI:1.4-3.9), Spaniards (HR:2.5; 95%CI:1.6-4.0), Gràcia district residents (HR:2.0; 95%CI:1.1-3.7), illiterate/primary education individuals (HR:1.5; IC95%:1.1-2.2), and <200 CD4 subjects (HR:1.8; 95%CI:1.2-3.0). HIV-related CoD were due to infections (48%): most common in men who have sex with men (MSM) (63%), followed by HTS women (60%). Non-HIV-related CoD were cancer (29%): more prevalent in men (32%), people with have secondary/university studies (39%) and HTS men (50%); cardiovascular diseases (22%): in HTS women (57%) and illiterate/primary education individuals (35%) and; liver diseases (19%): in IDU (37%). Abstract conclusion Mortality was associated with being IDU, HTS man, Spaniard, with low educational level and damaged immune system. CoD frequencies in HIVrelated and non-HIV-related were simila

Investigation of Mammographic Breast Density as a Risk Factor for Ovarian Cancer

BACKGROUND: Endogenous hormones and growth factors that increase mammographic breast density could increase ovarian cancer risk. We examined whether high breast density is associated with ovarian cancer risk. METHODS: We conducted a cohort study of 724603 women aged 40 to 79 years with 2506732 mammograms participating in the Breast Cancer Surveillance Consortium from 1995 to 2009. Incident epithelial ovarian cancer was diagnosed in 1373 women. We used partly conditional Cox regression to estimate the association between breast density and 5-year risk of incident epithelial ovarian cancer overall and stratified by 10-year age group. All statistical tests were two-sided. RESULTS: Compared with women with scattered fibroglandular densities, women with heterogeneously dense and extremely dense breast tissue had 20% and 18% increased 5-year risk of incident epithelial ovarian cancer (hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 1.06 to 1.36; HR = 1.18, 95% CI = 0.93 to 1.50, respectively; P (trend) = .01). Among women aged 50 to 59 years, we observed a trend in elevated risk associated with increased breast density (P (trend) = .02); women with heterogeneously and extremely dense breast tissue had 30% (HR = 1.30; 95% CI = 1.03 to 1.64) and 65% (HR = 1.65; 95% CI = 1.12 to 2.44) increased risk, respectively, compared with women with scattered fibroglandular densities. The pattern was similar but not statistically significant at age 40 to 49 years. There were no consistent patterns of breast density and ovarian cancer risk at age 60 to 79 years. CONCLUSIONS: Dense breast tissue was associated with a modest increase in 5-year ovarian cancer risk in women aged 50 to 59 years but was not associated with ovarian cancer at ages 40 to 49 or 60 to 79 years