General Directorate Public Health and Center for Public Health Research

Valencia, Spain

General Directorate Public Health and Center for Public Health Research

Valencia, Spain

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Domingo L.,IMIM Hospital del Mar Research Institute | Romero A.,IMIM Hospital del Mar Research Institute | Blanch J.,IMIM Hospital del Mar Research Institute | Salas D.,General Directorate Public Health and Center for Public Health Research | And 8 more authors.
Cancer Epidemiology | Year: 2013

Background: Women with a false-positive result after a screening mammogram have an increased risk of cancer detection in subsequent participations, especially after assessments involving cytology or biopsy. We aimed to compare women's personal characteristics, tumoral features and the radiological appearance of cancers with and without a previous false-positive result generated by additional imaging or invasive procedures. Methods: From 1996 to 2007, 111,098 women aged 45-69 years participated in four population-based breast cancer screening programs in Spain, and 1281 cancers were detected. We included all cancers detected in subsequent screenings (n= 703) and explored the occurrence of previous false-positive results. We identified false-positives requiring additional imaging or invasive procedures. Differences on tumoral features (invasiveness, tumor size, and lymph node status) and radiological appearance were assessed by Chi-square test, and agreement between the location of cancer and prior suspicious by Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the effect of previous screening results and age on the odds of presenting an in situ carcinoma. Results: Among the 703 cancers detected in subsequent screenings, 148 women (21.1%) had a previous false-positive result. Of these, 105 were by additional imaging and 43 by invasive procedures. Women with prior false-positive result requiring invasive assessment, compared to women with negative tests, and women with prior false-positive requiring additional imaging, had a higher proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p= 0.014) and microcalcifications (37.2%, 20.2%, 9.5%, respectively; p= 0.003). The proportion of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%, 13.0%, respectively; p= 0.001). Ipsilateral cancer was observed in 65.7% of cases with prior cytology or biopsy (k= 0.479; 95%CI: 0.330-0.794). Conclusion: A large number of in situ malignancies and calcification patterns were found among women with prior false-positive result in mammography screening requiring cytology or biopsies, suggesting progression from a previously benign lesion. © 2013 Elsevier Ltd.


Domingo L.,Hospital Del Mar | Domingo L.,CIBER ISCIII | Domingo L.,Autonomous University of Barcelona | Romero A.,Hospital Del Mar | And 17 more authors.
European Radiology | Year: 2011

Objectives: To compare tumour characteristics between cancers detected with screen-film mammography (SFM) and digital mammography (DM) and to evaluate changes in positive predictive values (PPVs) for further assessments, for invasive procedures and for distinct radiological patterns in recalled women. Methods: 242,838 screening mammograms (171,191 SFM and 71,647 DM) from 103,613 women aged 45-69 years, performed in four population-based breast cancer screening programmes in Spain, were included. The tumour characteristics and PPVs of each group were compared. Radiological patterns (masses, calcifications, distortions and asymmetries) among recalled women were described and PPVs were evaluated. Results: The percentages of ductal carcinoma in situ (DCIS) were higher in DM than in SFM both in the first [18.5% vs. 15.8%(p = 0.580)] and in successive screenings [23.2% vs. 15.7%(p = 0.115)]. PPVs for masses, asymmetries and calcifications were higher in DM, being statistically significant in masses (5.3% vs. 3.9%; proportion ratio: 1.37 95%CI: 1.08-1.72). Among cancers detected by calcifications, the percentage of DCIS was higher in DM (60.3% vs. 46.4%, p = 0.060). Conclusions: PPVs were higher when DM was used, both for further assessments and for invasive procedures, with similar cancer detection rates and no statistically significant differences in tumour characteristics. The greatest improvements in PPVs were found for masses. © 2011 European Society of Radiology.


Ascunce N.,CIBER ISCIII | Ederra M.,CIBER ISCIII | Delfrade J.,CIBER ISCIII | Baroja A.,Fundacion Rioja Salud | And 4 more authors.
European Radiology | Year: 2012

Objectives: Breast cancer screening is offered to 100% of the target population in Spain and intermediate mammograms (IMs) are sometimes indicated. This study was aimed at analysing the frequency of IMs, the factors determining their recommendation, and their impact on the risk of false-positive results and the detection rate. Methods: Data from 3,471,307 mammograms from Spanish breast cancer screening programmes were included. Results: 3.36% of the mammograms were IMs. The factors associated with the use of IMs were age, initial screening, previous invasive tests, a familial history of breast cancer and use of hormone replacement therapy. In screening episodes with an IM, the probability of a false-positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive procedures, a familial history of breast cancer or hormone replacement therapy use who were undergoing their initial screen, this probability was lower when IMs were performed. IMs always increased the detection rate. Conclusions: The factors prompting IMs should be characterised so that radiologists can systematise their recommendations according to the presence of the factors maximising the benefits and minimising the adverse effects of this procedure. Key Points : • Intermediate mammograms in breast screening offer potential benefits but also disadvantages. • Intermediate mammograms increase the false-positive rate except in specific groups. • Intermediate mammograms reduce the false-positive rate in younger women and initial screens. • Intermediate mammograms also reduce false-positive results in women with personal risk factors • Intermediate mammograms increase cancer detection mainly in women without risk factors. © 2011 European Society of Radiology.


de Juan I.,Polytechnic University of Valencia | Palanca S.,Polytechnic University of Valencia | Domenech A.,Polytechnic University of Valencia | Feliubadalo L.,Lhospitalet Of Llobregat Barcelona | And 24 more authors.
Familial Cancer | Year: 2015

Male breast cancer (MBC) is a rare disease that represents <1 % of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7 %), 95.9 % with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations. © 2015, Springer Science+Business Media Dordrecht.


PubMed | Institute of Genetics and Molecular Biology UVa CSIC, Lhospitalet Of Llobregat Barcelona, Fundacion Publica Galega de Medicina Xenomica SERGAS, University of Barcelona and 11 more.
Type: Journal Article | Journal: Familial cancer | Year: 2015

Male breast cancer (MBC) is a rare disease that represents <1% of all breast cancers (BCs). We analyze the results of a multicenter study performed in Spanish familial MBC including family history of hereditary breast and ovarian cancer syndrome (HBOCS) and clinicopathological features. We also study the relationship between BRCA1/BRCA2 mutational status in male relatives affected with cancer (MAC) and, family history and tumor types. The study included 312 men index cases with family history of HBOCS and 61 MAC BRCA1/2 mutation-carriers. Family history, histological grade (HG), clinicopathological and immunohistochemistry data were collected. BRCA1/2 mutation analyses were performed by direct sequencing or screening methods and the large rearrangements by multiplex ligation dependent probe amplification. We found 49 mutation-carriers (15.7%), 95.9% with BRCA2 mutations. BRCA2 mutation-carriers were associated with families with at least one MBC and one BC in female (type II; p = 0.05). Strong association were found between the presence of pathogenic mutations in MBCs and the advanced HG (p = 0.003). c.658_659delTG, c.2808_2811delACAA, c.6275_6276delTT and c.9026_9030delATCAT were the most prevalent mutations. In 61 MAC we found 20 mutations in BRCA1 and 41 in BRCA2. For MAC we show that mutational status was differentially associated with family history (p = 0.018) and tumor type, being BRCA2 mutations linked with BC and prostatic cancer (p = 0.018). MBC caused by BRCA1/2 mutations define two types of MBCs. The most frequent caused by BRCA2 mutation linked to type II families and the rarest one attributed to BRCA1 mutation. Tumor associated with MAC suggest that only BRCA2 mutations have to do with a specific type of cancer (BC and prostatic cancer); but the linkage to tumors is questionable for BRCA1 mutations .


Vilaprinyo E.,Biomedical Research Institute of Lleida IRBLLEIDA | Vilaprinyo E.,University of Lleida | Forne C.,Biomedical Research Institute of Lleida IRBLLEIDA | Forne C.,University of Lleida | And 51 more authors.
PLoS ONE | Year: 2014

The one-size-fits-all paradigm in organized screening of breast cancer is shifting towards a personalized approach. The present study has two objectives: 1) To perform an economic evaluation and to assess the harm-benefit ratios of screening strategies that vary in their intensity and interval ages based on breast cancer risk; and 2) To estimate the gain in terms of cost and harm reductions using risk-based screening with respect to the usual practice. We used a probabilistic model and input data from Spanish population registries and screening programs, as well as from clinical studies, to estimate the benefit, harm, and costs over time of 2,624 screening strategies, uniform or risk-based. We defined four risk groups, low, moderate-low, moderate-high and high, based on breast density, family history of breast cancer and personal history of breast biopsy. The risk-based strategies were obtained combining the exam periodicity (annual, biennial, triennial and quinquennial), the starting ages (40, 45 and 50 years) and the ending ages (69 and 74 years) in the four risk groups. Incremental cost-effectiveness and harm-benefit ratios were used to select the optimal strategies. Compared to risk-based strategies, the uniform ones result in a much lower benefit for a specific cost. Reductions close to 10% in costs and higher than 20% in false-positive results and overdiagnosed cases were obtained for risk-based strategies. Optimal screening is characterized by quinquennial or triennial periodicities for the low or moderate risk-groups and annual periodicity for the high-risk group. Risk-based strategies can reduce harm and costs. It is necessary to develop accurate measures of individual risk and to work on how to implement risk-based screening strategies. © 2014 Vilaprinyo et al.


Roman R.,Mar Teaching Hospital | Roman R.,Consortium for Biomedical Research in Epidemiology and Public Health | Sala M.,Mar Teaching Hospital | Sala M.,Consortium for Biomedical Research in Epidemiology and Public Health | And 13 more authors.
Breast Cancer Research and Treatment | Year: 2011

False-positive results may influence adherence to mammography screening. The effectiveness of breast cancer screening is closely related to adequate adherence among the target population. The objective of this study was to evaluate how false-positives and women's characteristics affect the likelihood of reattendance at routine breast cancer screening in a sequence of routine screening invitations. We performed a retrospective cohort study of 1,371,218 women aged 45-69 years, eligible for the next routine screening, who underwent 4,545,346 screening mammograms from 1990 to 2006. We estimated the likelihood of attendance at seven sequential screening mammograms. Multilevel discrete time hazard models were used to estimate the effect of false-positive results on reattendance, and the odds ratios (OR) of non-attendance for the women's personal characteristics studied. The overall reattendance rate at the second screening was 81.7% while at the seventh screening was 95.6%. At the second screening invitation reattendance among women with and without a false-positive mammogram was 79.3 vs. 85.3%, respectively. At the fourth and seventh screenings, these percentages were 86.3 vs. 89.9% and 94.6 vs. 96.0%, respectively. The study variables associated with a higher risk of failing to participate in subsequent screenings were oldest age (OR = 8.48; 95% CI: 8.31-8.65), not attending their first screening invitation (OR = 1.12; 95% CI: 1.11-1.14), and previous invasive procedures (OR = 1.09; 95% CI: 1.07-1.10). The risk of non-attendance was lower in women with a familial history of breast cancer (OR = 0.97; 95% CI: 0.96-0.99), and those using hormone replacement therapy (OR = 0.96; 95% CI: 0.94-0.97). In conclusion, reattendance was lower in women with false-positive mammograms than in those with negative results, although this difference decreased with the number of completed screening participations, suggesting that abnormal results in earlier screenings more strongly influence behavior. These findings may be useful in providing women with accurate information and in improving the effectiveness of screening programs. © Springer Science+Business Media, LLC. 2011.


PubMed | Autonomous University of Barcelona, Breast Imaging, General Directorate Public Health and Center for Public Health Research, Hospital Of Santa Caterina and 5 more.
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2015

In the context of a population-based screening program, we aimed to evaluate the major mammographic features and clinicopathological characteristics of breast tumors at diagnosis and the associations between them, focusing on tumors with the worst prognosis. We analyzed cancers diagnosed in a cohort of 645,764 women aged 45-69 years participating in seven population-based screening programs in Spain, between January 1, 2000 and December 31, 2006 and followed up until June 2009. We included all interval cancers and a sample of screen-detected cancers, whether invasive or in situ. We compared tumor-related information and breast density for different phenotypes (Triple-negative (TN), HER2+, Luminal B and Luminal A) in screen-detected and interval cancers. We used Chi-square or Fishers exact test to compare major mammographic features of invasive versus in situ tumors, of screen-detected versus interval cancers, and of different types of interval cancers. We included 2582 tumors (1570 screen-detected and 1012 interval cancers). There were significant differences in the distribution of most clinicopathological variables between screen-detected and interval cancers. Invasive TN interval tumors were more common than other phenotypes in breasts with low mammographic density; three-quarters of these tumors presented as masses without associated calcifications. HER2+ tumors were more common in denser breasts and were associated with calcifications and multifocality. Architectural distortion was more common in Luminal A and Luminal B tumors. Certain radiologic findings are associated with pre-invasive lesions; these differ among invasive tumor phenotypes. We corroborate that TN and HER2+ cancers have distinctive appearances also in the context of population-based screening programs. This information can be useful for establishing protocols for diagnostic strategies in screening units.


Bare M.,Clinical Epidemiology and Cancer Screening | Bare M.,Autonomous University of Barcelona | Tora N.,Clinical Epidemiology and Cancer Screening | Salas D.,General Directorate Public Health and Center for Public Health Research | And 11 more authors.
Breast Cancer Research and Treatment | Year: 2015

In the context of a population-based screening program, we aimed to evaluate the major mammographic features and clinicopathological characteristics of breast tumors at diagnosis and the associations between them, focusing on tumors with the worst prognosis. We analyzed cancers diagnosed in a cohort of 645,764 women aged 45–69 years participating in seven population-based screening programs in Spain, between January 1, 2000 and December 31, 2006 and followed up until June 2009. We included all interval cancers and a sample of screen-detected cancers, whether invasive or in situ. We compared tumor-related information and breast density for different phenotypes (Triple-negative (TN), HER2+, Luminal B and Luminal A) in screen-detected and interval cancers. We used Chi-square or Fisher’s exact test to compare major mammographic features of invasive versus in situ tumors, of screen-detected versus interval cancers, and of different types of interval cancers. We included 2582 tumors (1570 screen-detected and 1012 interval cancers). There were significant differences in the distribution of most clinicopathological variables between screen-detected and interval cancers. Invasive TN interval tumors were more common than other phenotypes in breasts with low mammographic density; three-quarters of these tumors presented as masses without associated calcifications. HER2+ tumors were more common in denser breasts and were associated with calcifications and multifocality. Architectural distortion was more common in Luminal A and Luminal B tumors. Certain radiologic findings are associated with pre-invasive lesions; these differ among invasive tumor phenotypes. We corroborate that TN and HER2+ cancers have distinctive appearances also in the context of population-based screening programs. This information can be useful for establishing protocols for diagnostic strategies in screening units. © 2015, Springer Science+Business Media New York.

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