Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study

It 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. METHODS: BC 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. RESULTS: MD 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. CONCLUSIONS: Our 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.This work was supported by research grants from Eli Lilly and Company (EV1 1082/08); and the Spanish Federation of Breast Cancer Patients (Federación Española de Cáncer de Mama) (FECMA 485 EPY 1170-10).S

Recalibration of the Gail model for predicting invasive breast cancer risk in Spanish women: a population-based cohort study.

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.The study was supported in part by a research Grant from Eli Lilly and Company (EV1 1082/08).S

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

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