Search

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect., (Copyright © 2012 UICC.)

Background: Mammographic breast density and endogenous sex-hormone levels are both strong risk factors for breast cancer. This study investigated whether there is evidence for a shared genetic basis between these risk factors., Methods: Using data on 1,286 women from 617 families, we estimated the heritabilities of serum estradiol, testosterone, and sex-hormone binding globulin (SHBG) levels and of three measures of breast density (dense area, nondense area, and percentage density). We tested for associations between hormone levels and density measures and estimated the genetic and environmental correlations between pairs of traits using variance and covariance components models and pedigree-based maximum likelihood methods., Results: We found no significant associations between estradiol, testosterone, or SHBG levels and any of the three density measures, after adjusting for body mass index (BMI). The estimated heritabilities were 63%, 66%, and 65% for square root-transformed adjusted percentage density, dense area, and nondense area, respectively, and 40%, 25%, and 58% for log-transformed-adjusted estradiol, testosterone, and SHBG. We found no evidence of a shared genetic basis between any hormone levels and any measure of density, after adjusting for BMI. The negative genetic correlation between dense and nondense areas remained significant even after adjustment for BMI and other covariates (ρ = -0.34; SE = 0.08; P = 0.0005)., Conclusions: Breast density and sex hormones can be considered as independent sets of traits., Impact: Breast density and sex hormones can be used as intermediate phenotypes in the search for breast cancer susceptibility loci.

Higher circulating insulin-like growth factor I (IGF-1) levels have been associated with higher mammographic density among women in some, but not all studies. Also, few studies have examined the association between mammographic density and circulating growth hormone (GH) in premenopausal women. We conducted a cross-sectional study among 783 premenopausal women and 436 postmenopausal women who were controls in breast cancer case-control studies nested in the Nurses' Health Study (NHS) and NHSII. Participants provided blood samples in 1989-1990 (NHS) or in 1996-1999 (NHSII), and mammograms were obtained near the time of blood draw. Generalized linear models were used to assess the associations of IGF-1, IGF-binding protein-3 (IGFBP-3), IGF-1:IGFBP-3 ratio, and GH with percent mammographic density, total dense area, and total non-dense area. Models were adjusted for potential confounders including age and body mass index (BMI), among others. We also assessed whether the associations varied by age or BMI. In both pre- and postmenopausal women, percent mammographic density was not associated with plasma levels of IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 ratio. In addition, GH was not associated with percent density among premenopausal women in the NHSII. Similarly, total dense area and non-dense area were not significantly associated with any of these analytes. In postmenopausal women, IGF-1 was associated with higher percent mammographic density among women with BMI <25 kg/m(2), but not among overweight/obese women. Overall, plasma IGF-1, IGFBP-3, and GH levels were not associated with mammographic density in a sample of premenopausal and postmenopausal women.

Background: As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies., Methods: Histological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%)., Results: The weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density., Conclusions: Mammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.

Introduction: Mammographic density is a strong risk factor for breast cancer. Image acquisition technique varies across mammograms to limit radiation and produce a clinically useful image. We examined whether acquisition technique parameters at the time of mammography were associated with mammographic density and whether the acquisition parameters confounded the density and breast cancer association., Methods: We examined this question within the Mayo Mammography Health Study (MMHS) cohort, comprised of 19,924 women (51.2% of eligible) seen in the Mayo Clinic mammography screening practice from 2003 to 2006. A case-cohort design, comprising 318 incident breast cancers diagnosed through December 2009 and a random subcohort of 2,259, was used to examine potential confounding of mammogram acquisition technique parameters (x-ray tube voltage peak (kVp), milliampere-seconds (mAs), thickness and compression force) on the density and breast cancer association. The Breast Imaging Reporting and Data System four-category tissue composition measure (BI-RADS) and percent density (PD) (Cumulus program) were estimated from screen-film mammograms at time of enrollment. Spearman correlation coefficients (r) and means (standard deviations) were used to examine the relationship of density measures with acquisition parameters. Hazard ratios (HR) and C-statistics were estimated using Cox proportional hazards regression, adjusting for age, menopausal status, body mass index and postmenopausal hormones. A change in the HR of at least 15% indicated confounding., Results: Adjusted PD and BI-RADS density were associated with breast cancer (p-trends < 0.001), with a 3 to 4-fold increased risk in the extremely dense vs. fatty BI-RADS categories (HR: 3.0, 95% CI, 1.7 - 5.1) and the ≥ 25% vs. ≤ 5% PD categories (HR: 3.8, 95% CI, 2.5 - 5.9). Of the acquisition parameters, kVp was not correlated with PD (r = 0.04, p = 0.07). Although thickness (r = -0.27, p < 0.001), compression force (r = -0.16, p < 0.001), and mAs (r = -0.06, p = 0.008) were inversely correlated with PD, they did not confound the PD or BI-RADS associations with breast cancer and their inclusion did not improve discriminatory accuracy. Results were similar for associations of dense and non-dense area with breast cancer., Conclusions: We confirmed a strong association between mammographic density and breast cancer risk that was not confounded by mammogram acquisition technique.

Objective: The aim of this study was to evaluate reader variability in screening mammograms according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessment and breast density categories., Methods: A stratified random sample of 100 mammograms was selected from a population-based breast cancer screening programme in Barcelona, Spain: 13 histopathologically confirmed breast cancers and 51 with true-negative and 36 with false-positive results. 21 expert radiologists from radiological units of breast cancer screening programmes in Catalonia, Spain, reviewed the mammography images twice within a 6-month interval. The readers described each mammography using BI-RADS assessment and breast density categories. Inter- and intraradiologist agreement was assessed using percentage of concordance and the kappa (κ) statistic., Results: Fair interobserver agreement was observed for the BI-RADS assessment [κ=0.37, 95% confidence interval (CI) 0.36-0.38]. When the categories were collapsed in terms of whether additional evaluation was required (Categories III, 0, IV, V) or not (I and II), moderate agreement was found (κ=0.53, 95% CI 0.52-0.54). Intra-observer agreement for BI-RADS assessment was moderate using all categories (κ=0.53, 95% CI 0.50-0.55) and substantial on recall (κ=0.66, 95% CI 0.63-0.70). Regarding breast density, inter- and intraradiologist agreement was substantial (κ=0.73, 95% CI 0.72-0.74 and κ=0.69, 95% CI 0.68-0.70, respectively)., Conclusion: We observed a substantial intra-observer agreement in the BI-RADS assessment but only moderate interobserver agreement. Both inter- and intra-observer agreement in mammographic interpretation of breast density was substantial. Advances in knowledge Educational efforts should be made to decrease radiologists' variability in BI-RADS assessment interpretation in population-based breast screening programmes.

Mammographic density is a strong and independent risk factor for breast cancer and is considered an intermediate marker of risk. The major predictors of premenopausal mammographic density, however, have yet to be fully elucidated. To test the hypothesis that urinary estrogen metabolism profiles are associated with mammographic density, we conducted a cross-sectional study among 352 premenopausal women in the Nurses' Health Study II (NHSII). We measured average percent mammographic density using a computer-assisted method. In addition, we assayed 15 estrogens and estrogen metabolites (jointly termed EM) in luteal-phase urine samples. We used multivariable linear regression to quantify the association of average percent density with quartiles of each individual EM as well as the sum of all EM (total EM), EM groups defined by metabolic pathway, and pathway ratios. In multivariable models controlling for body mass index and other predictors of breast density, women in the top quartile of total EM had an average percent density 3.4 percentage points higher than women in the bottom quartile (95 % confidence interval: -1.1, 8.0; p trend = 0.08). A non-significant positive association was noted for the 2-hydroxylation pathway catechols (breast density was 4.0 percentage points higher in top vs. bottom quartile; p trend = 0.06). In general, we observed no associations with parent estrogens or the 4- or 16-hydroxylation pathways or pathway ratios. These results suggest that urinary luteal estrogen profiles are not strongly associated with premenopausal mammographic density. If these profiles are associated with breast cancer risk, they may not act through influences on breast density.

Introduction: Mammographic density (MD) is one of the strongest known breast cancer risk factors. Estrogen and progestin therapy (EPT) has been associated with increases in MD. Dense breast tissue is characterized by increased stromal tissue and (to a lesser degree) increased numbers of breast epithelial cells. It is possible that genetic factors modify the association between EPT and MD, and that certain genetic variants are particularly important in determining MD in hormone users. We evaluated the association between MD and 340 tagging single nucleotide polymorphisms (SNPs) from about 30 candidate genes in hormone metabolism/growth factor pathways among women who participated in the Norwegian Breast Cancer Screening Program (NBCSP) in 2004., Methods: We assessed MD on 2,036 postmenopausal women aged 50 to 69 years using a computer-assisted method (Madena, University of Southern California) in a cross-sectional study. We used linear regression to determine the association between each SNP and MD, adjusting for potential confounders. The postmenopausal women were stratified into HT users (EPT and estrogen-only) and non-users (never HT)., Results: For current EPT users, there was an association between a variant in the prolactin gene (PRL; rs10946545) and MD (dominant model, Bonferroni-adjusted P (Pb) = 0.0144). This association remained statistically significant among current users of norethisterone acetate (NETA)-based EPT, a regimen common in Nordic countries. Among current estrogen-only users (ET), there was an association between rs4670813 in the cytochrome P450 gene (CYP1B1) and MD (dominant model, Pb = 0.0396). In never HT users, rs769177 in the tumor necrosis factor (TNF) gene and rs1968752 in the region of the sulfotransferase gene (SULT1A1/SULT1A2), were significantly associated with MD (Pb = 0.0202; Pb = 0.0349)., Conclusions: We found some evidence that variants in the PRL gene were associated with MD in current EPT and NETA users. In never HT users, variants in the TNF and SULT1A1/SULT1A2 genes were significantly associated with MD. These findings may suggest that several genes in the hormone metabolism and growth factor pathways are implicated in determining MD.

Gene expression analysis of healthy postmenopausal women in a prospective clinical study indicated that genes encoding for epithelial proliferation markers Ki-67 and progesterone receptor B mRNA are differentially expressed in women using hormone therapy (HT) with natural versus synthetic estrogens. Two 28-day cycles of daily estradiol (E2) gel 1.5 mg and oral micronized progesterone (P) 200 mg/day for the last 14 days of each cycle did not significantly increase breast epithelial proliferation (Ki-67 MIB-1 positive cells) at the cell level nor at the mRNA level (MKI-67 gene). A borderline significant beneficial reduction in anti-apoptotic protein bcl-2, favouring apoptosis, was also seen followed by a slight numeric decrease of its mRNA. By contrast, two 28-day cycles of daily oral conjugated equine estrogens (CEE) 0.625 mg and oral medroxyprogesterone acetate (MPA) 5 mg for the last 14 days of each cycle significantly increased proliferation at both the cell level and at the mRNA level, and significantly enhanced mammographic breast density, an important risk factor for breast cancer. In addition, CEE/MPA affected around 2,500 genes compared with just 600 affected by E2/P. These results suggest that HT with natural estrogens affects a much smaller number of genes and has less-adverse effects on the normal breast in vivo than conventional, synthetic therapy.

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥ 12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.

Introduction: Mammographic density (MD) is a strong, independent risk factor for breast cancer, but measuring MD is time consuming and reader dependent. Objective MD measurement in a high-throughput fashion would enable its wider use as a biomarker for breast cancer. We use a public domain image-processing software for the fully automated analysis of MD and penalized regression to construct a measure that mimics a well-established semiautomated measure (Cumulus). We also describe measures that incorporate additional features of mammographic images for improving the risk associations of MD and breast cancer risk., Methods: We randomly partitioned our dataset into a training set for model building (733 cases, 748 controls) and a test set for model assessment (765 cases, 747 controls). The Pearson product-moment correlation coefficient (r) was used to compare the MD measurements by Cumulus and our automated measure, which mimics Cumulus. The likelihood ratio test was used to validate the performance of logistic regression models for breast cancer risk, which included our measure capturing additional information in mammographic images., Results: We observed a high correlation between the Cumulus measure and our measure mimicking Cumulus (r = 0.884; 95% CI, 0.872 to 0.894) in an external test set. Adding a variable, which includes extra information to percentage density, significantly improved the fit of the logistic regression model of breast cancer risk (P = 0.0002)., Conclusions: Our results demonstrate the potential to facilitate the integration of mammographic density measurements into large-scale research studies and subsequently into clinical practice.

Introduction: Over the last decade several breast cancer risk alleles have been identified which has led to an increased interest in individualised risk prediction for clinical purposes., Methods: We investigate the performance of an up-to-date 18 breast cancer risk single-nucleotide polymorphisms (SNPs), together with mammographic percentage density (PD), body mass index (BMI) and clinical risk factors in predicting absolute risk of breast cancer, empirically, in a well characterised Swedish case-control study of postmenopausal women. We examined the efficiency of various prediction models at a population level for individualised screening by extending a recently proposed analytical approach for estimating number of cases captured., Results: The performance of a risk prediction model based on an initial set of seven breast cancer risk SNPs is improved by additionally including eleven more recently established breast cancer risk SNPs (P = 4.69 × 10-4). Adding mammographic PD, BMI and all 18 SNPs to a Swedish Gail model improved the discriminatory accuracy (the AUC statistic) from 55% to 62%. The net reclassification improvement was used to assess improvement in classification of women into low, intermediate, and high categories of 5-year risk (P = 8.93 × 10-9). For scenarios we considered, we estimated that an individualised screening strategy based on risk models incorporating clinical risk factors, mammographic density and SNPs, captures 10% more cases than a screening strategy using the same resources, based on age alone. Estimates of numbers of cases captured by screening stratified by age provide insight into how individualised screening programs might appear in practice., Conclusions: Taken together, genetic risk factors and mammographic density offer moderate improvements to clinical risk factor models for predicting breast cancer.

Introduction: Increased mammographic breast density is one of the strongest risk factors for breast cancer. While two-thirds of the variation in mammographic density appears to be genetically influenced, few variants have been identified. We examined the association of inherited variation in genes from pathways that mediate cell division with percent mammographic density (PMD) adjusted for age, body mass index (BMI) and postmenopausal hormones, in two studies of healthy postmenopausal women., Methods: We investigated 2,058 single nucleotide polymorphisms (SNPs) in 378 genes involved in regulation of mitosis for associations with adjusted PMD among 484 unaffected postmenopausal controls (without breast cancer) from the Mayo Clinic Breast Cancer Study (MCBCS) and replicated the findings in postmenopausal controls (n = 726) from the Singapore and Sweden Breast Cancer Study (SASBAC) study. PMD was assessed in both studies by a computer-thresholding method (Cumulus) and linear regression approaches were used to assess the association of SNPs and PMD, adjusted for age, BMI and postmenopausal hormones. A P-value threshold of 4.2 × 10-5 based on a Bonferroni correction of effective number of independent tests was used for statistical significance. Further, a pathway-level analysis was conducted of all 378 genes using the self-contained gene-set analysis method GLOSSI., Results: A variant in PRPF4, rs10733604, was significantly associated with adjusted PMD in the MCBCS (P = 2.7 × 10-7), otherwise, no single SNP was associated with PMD. Additionally, the pathway analysis provided no evidence of enrichment in the number of associations observed between SNPs in the mitotic genes and PMD (P = 0.60). We evaluated rs10733604 (PRPF4), and 73 other SNPs at P < 0.05 from 51 genes in the SASBAC study. There was no evidence of an association of rs10733604 (PRPF4) with adjusted PMD in SASBAC (P = 0.23). There were, however, consistent associations (P < 0.05) of variants at the putative locus, LOC375190, Aurora B kinase (AURKB), and Mini-chromosome maintenance complex component 3 (MCM3) with adjusted PMD, although these were not statistically significant., Conclusions: Our findings do not support a role of inherited variation in genes involved in regulation of cell division and adjusted percent mammographic density in postmenopausal women.

We present a patient with features of Ulnar Mammary syndrome (UMS) consisting of bilateral ulnar defects, inverted nipples, short stature with associated growth hormone deficiency, and cryptorchidism. Our patient also had a hypoplastic anterior pituitary and an ectopic posterior pituitary gland, ventricular septal defect (VSD), and cardiac conduction defects consistent with Wolff-Parkinson-White (WPW) syndrome. Although TBX3 is known to be expressed in both the developing heart and the pituitary gland, conduction defects and anatomical pituitary abnormalities have not been previously described in UMS. This may, in part, be due to the fact that these features are not actively sought in individuals with UMS. Because these new findings have important clinical implications, we suggest that clinicians caring for individuals with UMS offer brain imaging, growth hormone testing, and cardiac arrhythmia screening. The diagnosis of UMS was confirmed on mutation analysis of TBX3. The mother of the propositus was also found to carry the same mutation, although she did not show the classical features of UMS. Therefore, our report also supports the variable expressivity of UMS within the same family.

Aim: Inadequate androgen activity is a likely cause of cryptorchidism in humans, affecting inguinoscrotal testicular descent. Flutamide, a nonsteroidal antiandrogen, produces cryptorchidism in rats. We aimed to determine the anatomical and histologic effects of flutamide., Methods: Time-mated Sprague-Dawley female rats were injected subcutaneously with flutamide (75 mg/kg in sunflower oil) on days 16 to 19 of pregnancy. Embryonic (E) and postnatal (P) male offspring were collected (E16, E19, P0, P2, P4, P8) in control and flutamide-treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five-micrometer-thick sections were prepared for hematoxylin and eosin, trichrome and immunohistochemical stains (Desmin, TuJ1, Ki67). This identified muscle and neural cells and areas of cell proliferation., Results: Postnatally, the gubernaculum in flutamide-treated rats had more mesenchyme and muscle than controls. Gubernacular eversion failed, and mammary tissue persisted around the gubernaculum in flutamide-treated rats. Flutamide had no effect on embryonic gubernacular anatomy and histology., Conclusions: Prenatal androgens altered postnatal gubernacular anatomy and histology in the postnatal period. Our findings indicate that the failure of gubernacular differentiation and migration may be because of the ongoing presence of mammary tissue in the region of the external inguinal ring.

Background: Many chest wall deformities have a characteristic radiologic appearance that can be the basis for a definitive diagnosis. Consequently, imaging techniques have fundamental roles in the detection, location, and characterization of these disorders., Objective: The authors propose a clinical and radiographic Poland syndrome (CRPS) classification system and possible treatment algorithm for the thoracic manifestations of Poland syndrome (PS) in women, based on both clinical examinations and imaging studies., Methods: A retrospective study was conducted of 28 female patients evaluated over 17 years in the 28th Infirmary, Plastic and Reconstructive Surgery Division of the Hospital Santa Casa da Misericórdia do Rio de Janeiro, Rio de Janeiro, Brazil. After clinical examination, all patients underwent radiographic examination with chest radiographs, conventional computed tomography scans, magnetic resonance imaging and, in some cases, additional imaging studies. All clinical and radiologic variables were compiled in a database and used in the classification system, which included three levels of disease severity., Results: Based on the CRPS classification of the 28 female patients, 10 patients had first-degree PS, 14 patients had second-degree PS, and four patients had third-degree PS. Eighteen patients underwent surgical correction; a total of 39 surgical procedures were performed using the CRPS algorithm., Conclusions: Identification of the severity of PS using the proposed classification system provided an accurate study of each patient and enabled better planning for the surgical correction of functional and aesthetic deformities.

Objective: To investigate the correction of secondary breast deformities after removement of injected polyacrylamide hydrophilic gel (PAHG)., Methods: From March 2003 to March 2008, 100 patients with bilateral breast augmentation with injected PAHG underwent operation to remove the PAHG. The age of patients ranged from 35 to 50 years. Ultrasound and MRI were performed before operation to show the distribution of PAHG and the muscle infiltration around the PAHG. According to the PAHG distribution, muscle infiltration, skin elasticity, infection and PAHG residue, the patients were treated respectively with breast implants at the same stage or at the second stage, or without implants., Results: The patients were followed up for 3 months to 3 years. The percentage of satisfactory, median satisfactory and dissatisfactory was 90%, 9%, and 1%. In the median satisfactory group, 3 breasts in 3 cases showed slight capsular contracture (Baker II), 8 implants in 6 cases were palpable on the lower pole of the breasts. The middle-aged patient in dissatisfactory group was not satisfied with the high-projected implants shape which were chosen by herself and placed at the second stage. Then implants were removed. There was no complication of implant hernia, infection, wound disruption, or asymmetry., Conclusions: The secondary breast deformities could be corrected by breast augmentation with implants. Both breast appearance and the psychological affection can be improved.

Objective: Supernumerary nipples (SNN), or polythelia, are the most common form of the accessory mammary tissue malformation. The frequency of this condition ranges from 0.2% to 5.6% depending on various factors. This condition is associated with several anomalies, although this association is often controversial. The aim of this study was to evaluate the association between SNN and kidney/urinary tract (K/UT) anomalies, where anomalies is taken to mean functional disorders, malformations and diseases., Material and Methods: A case-control study was performed. The study evaluated 166 children (case group) referred to the Pediatric Nephrology Unit of the Department of Pediatrics of the Catholic University of Rome and 182 children (control group) admitted to the Department of Pediatrics because of pathologies not involving the urinary tract., Results: There were 11 children with SNN in the case group, and only two patients in the control group (6.62% vs 1.09%, p<0.05)., Conclusion: The results show a high incidence of K/UT anomalies in children with SNN, and therefore K/UT should be investigated in this specific population.

Amazia, the absence of the mammary gland, is a very rare congenital anomaly of the breasts. Bilateral absence of the breasts may occur as an isolated anomaly or may be associated with a syndrome or a cluster of other anomalies. Although the literature examining pediatric breast abnormalities is replete with case reports and series, bilateral amazia together with skeletal anomalies has not yet been described. An unusual case of amazia associated with face, limb, and vertebrae anomalies is presented.