IntroductionIt is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis.MethodsBC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression.ResultsMD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration.ConclusionsOur results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.

The Gail model for predicting the absolute risk of invasive breast cancer has been validated extensively in US populations, but its performance in the international setting remains uncertain. We evaluated the predictive accuracy of the Gail model in 54,649 Spanish women aged 45–68 years who were free of breast cancer at the 1996–1998 baseline mammographic examination in the population-based Navarre Breast Cancer Screening Program. Incident cases of invasive breast cancer and competing deaths were ascertained until the end of 2005 (average follow-up of 7.7 years) through linkage with population-based cancer and mortality registries. The Gail model was tested for calibration and discrimination in its original form and after recalibration to the lower breast cancer incidence and risk factor prevalence in the study cohort, and compared through cross-validation with a Navarre model fully developed from this cohort. The original Gail model overpredicted significantly the 835 cases of invasive breast cancer observed in the cohort (ratio of expected to observed cases 1.46, 95 % CI 1.36–1.56). The recalibrated Gail model was well calibrated overall (expected-to-observed ratio 1.00, 95 % CI 0.94–1.07), but it tended to underestimate risk for women in low-risk quintiles and to overestimate risk in high-risk quintiles (P = 0.01). The Navarre model showed good cross-validated calibration overall (expected-to-observed ratio 0.98, 95 % CI 0.92–1.05) and in different cohort subsets. The Navarre and Gail models had modest cross-validated discrimination indexes of 0.542 (95 % CI 0.521–0.564) and 0.544 (95 % CI 0.523–0.565), respectively. Although the original Gail model cannot be applied directly to populations with different underlying rates of invasive breast cancer, it can readily be recalibrated to provide unbiased estimates of absolute risk in such populations. Nevertheless, its limited discrimination ability at the individual level highlights the need to develop extended models with additional strong risk factors.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-013-2428-y) contains supplementary material, which is available to authorized users.

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RESUMENFundamento. Existe un consenso general en la recomendación de aplicar con carácter poblacional programas de cribado de cáncer de mama. El Departamento de Salud puso en marcha en el año 1990 un Programa de Detección Precoz de Cáncer de Mama, con el objetivo de disminuir la mortalidad por este tumor, que en este momento está finalizando su séptima vuelta. El presente trabajo tiene como objetivo analizar los resultados obtenidos, describiendo los principales indicadores de proceso y predictores de impacto según los factores más determinantes. Material y métodos.Se han recopilado los datos de las exploraciones de cribado realizadas desde el comienzo del programa hasta el 31 de diciembre de 2002 clasificando por edad en el momento de la exploración, tipo de exploración y vuelta.Resultados. Durante el período se han realizado 354.575 exploraciones. Indicadores de proceso: en el 11,22% se recomendó realizar una exploración adicional. El 0,67% de las mujeres han sido enviadas a unidades hospitalarias para valoración diagnóstica. Se ha confirmado un tumor maligno en el 0,34% de las mujeres exploradas. A 8,37% de las mujeres se les ha recomendado realizar una exploración intermedia antes de la nueva de cribado.Indicadores predictores de impacto: la captación global es de 88,68%, la participación global de 87,91% y la adherencia al programa de 96,32%. La tasa de detección alcanza la cifra de 3,95 por 1.000 mujeres exploradas. De los tumores detectados, 19,17% son intraductales, y 37,23% de los invasivos tienen un tamaño igual o inferior a 10 mm. El 74,89% del total de tumores no presenta invasión ganglionar. Conclusiones.Considerando las referencias que para programas de cribado establece la Unión Europea, todos los indicadores predictores calculados superan los estándares exigidos.Palabras Clave. Cáncer de mama. Cribado poblacional. Indicadores. Evaluación. ABSTRACTBackground. There is a general consensus on the recommendation of applying breast cancer screening programs to the population. In March 1990, the Health Department set in motion a Program for the Early Detection of Breast Cancer, with the aim of reducing mortality due to this tumour. At present, the program is reaching the end of its seventh round. The present study aims to analyze the results obtained, describing the principal indicators of the process and the impact predictions according to the most determinant factors.