Performance measures of 8,169,869 examinations in the National Breast Cancer Screening Program in Taiwan, 2004-2020.

BACKGROUND: The benefits of mammographic screening have been shown to include a decrease in mortality due to breast cancer. Taiwan's Breast Cancer Screening Program is a national screening program that has offered biennial mammographic breast cancer screening for women aged 50-69 years since 2004 and for those aged 45-69 years since 2009, with the implementation of mobile units in 2010. The purpose of this study was to compare the performance results of the program with changes in the previous (2004-2009) and latter (2010-2020) periods. METHODS: A cohort of 3,665,078 women who underwent biennial breast cancer mammography screenings from 2004 to 2020 was conducted, and data were obtained from the Health Promotion Administration, Ministry of Health and Welfare of Taiwan. We compared the participation of screened women and survival rates from breast cancer in the earlier and latter periods across national breast cancer screening programs. RESULTS: Among 3,665,078 women who underwent 8,169,869 examinations in the study population, the screened population increased from 3.9% in 2004 to 40% in 2019. The mean cancer detection rate was 4.76 and 4.08 cancers per 1000 screening mammograms in the earlier (2004-2009) and latter (2010-2020) periods, respectively. The 10-year survival rate increased from 89.68% in the early period to 97.33% in the latter period. The mean recall rate was 9.90% (95% CI: 9.83-9.97%) in the early period and decreased to 8.15% (95%CI, 8.13-8.17%) in the latter period. CONCLUSIONS: The evolution of breast cancer screening in Taiwan has yielded favorable outcomes by increasing the screening population, increasing the 10-year survival rate, and reducing the recall rate through the participation of young women, the implementation of a mobile unit service and quality assurance program, thereby providing historical evidence to policy makers to plan future needs.

Breast cancer screening with digital breast tomosynthesis - 4 year experience and comparison with national data.

BACKGROUND: To determine if mammography combined with digital breast tomosynthesis (DBT), leads to superior performance in screening for breast cancer compared to digital mammography (DM) alone. METHODS: We retrospectively collected data from A) the results of population-based mammography-screening provided by the National Cancer Registry in Taiwan, and B) the results from all screening mammography performed with DBT from 2012 through 2015 at Kaohsiung Veterans General Hospital (VGHKS) since the institution of DBT at the end of 2011. This was compared data from 3 years with DM performed prior to DBT implementation. We calculated the results of medical audit of VGHKS and compared this with national data. Fisher's exact test is applied. RESULTS: VGHKS data demonstrated a higher cancer detection rate (CDR) and positive predictive value 1 (PPV 1) than the national average. Most prominently in the year 2014, our CDR was 120% better than that of the national average. CDR ranged from 6.3 to 8.1‰ prior to the introduction of DBT, and following DBT implementation this improved to 8.5-11.4‰, reflecting a mean increase of 32.2%. Early cancer detection was 50% higher and node negative rate was 25% higher than the national average of latest year. A 17.8% reduction in recall rate (RR) was achieved due to a decrease in unnecessary recall. CONCLUSION: There was a 32.2% increase in CDR and a 17.8% decrease in RR when DBT was used as an adjunct to DM, as compared to DM alone. CDRs were approximately twofold better than national average data. DBT was more effective at detecting cancer in ductal carcinoma in situ and stage 1.

The Values of Combined and Sub-Stratified Imaging Scores with Ultrasonography and Mammography in Breast Cancer Subtypes.

BACKGROUND AND OBJECTIVES: The Breast Imaging Reporting and Data System (BI-RADS) of Mammography (MG) and Ultrasonography (US) were equivalent to the "5-point score" and applied for combined and sub-stratified imaging assessments. This study evaluated the value of combined and sub-stratified imaging assessments with MG and US over breast cancer subtypes (BCS). MATERIALS AND METHODS: Medical records of 5,037 cases having imaging-guided core biopsy, performed from 2009 to 2012, were retrospectively reviewed. This study selected 1,995 cases (1,457 benign and 538 invasive cancer) having both MG and US before biopsy. These cases were categorized with the "5-point score" for their MG and US, and applied for combined and sub-stratified imaging assessments. Invasive cancers were classified on the basis of BCS, and correlated with combined and sub-stratified imaging assessments. RESULTS: These selected cases were evaluated by the "5-point score." MG, US, and combined and sub-stratified imaging assessments all revealed statistically significant (P < 0.001) incidence of malignancy. The sensitivity was increased in the combined imaging score (99.8%), and the specificity was increased in the sub-stratified combined score (75.4%). In the sub-stratified combined imaging assessment, all BCS can be classified with higher scores (abnormality hierarchy), and luminal B subtype showed the most salient result (hierarchy: higher, 95%; lower, 5%). CONCLUSIONS: Combined and sub-stratified imaging assessments can increase sensitivity and specificity of breast cancer diagnosis, respectively, and Luminal B subtype shows the best identification by sub-stratified combined imaging scoring.

Breast Nonmass Enhancement Detected with MRI: Uility and Lesion Characterization with Second-Look Ultrasonography.

The purpose of this study was to verify the utility of second-look ultrasonography (US) in evaluating nonmass enhancement (NME) lesions detected on breast magnetic resonance imaging (MRI) by analysing its correlation and imaging features. From July 2008 to June 2012, 102 consecutive MRI-detected NME lesions were subsequently evaluated with US. Lesions were evaluated according to the established Breast Imaging Reporting and Data System (BI-RADS) lexicon. The correlation between MRI-detected NME lesion characteristics, lesion size, histopathological findings and features at second-look US were analysed. Second-look US identified 44/102 (43%) of the NME lesions revealed by MRI. A US correlate was seen in 34/45 (76%) malignant lesions compared with 10/57 (18%) benign lesions (p < 0.0001). The likelihood of malignancy was significantly higher for NME lesions with a US correlate than lesions without: 34/44 (77%) versus 11/58 (19%) (p < 0.0001). The malignancy of the 44 (43%) MRI-detected NME lesions with a US correlate was significantly associated with US lesion margins and BI-RADS categories (p = 0.001 and 0.002 respectively). Second-look US of MRI-detected NME lesions is useful for decision-making as part of the diagnostic workup. Familiarity with the US features associated with malignancy improves the utility of US in the workup of these NME abnormalities.

Non-mass-like breast lesions at ultrasonography: feature analysis and BI-RADS assessment.

OBJECTIVE: To analyze the features of non-mass-like (NML) breast lesions on ultrasound (US) and determine their corresponding malignancy rate and to stratify these lesion patterns according to US BI-RADS categories. MATERIALS AND METHODS: One hundred sixty-four consecutive lesions were retrospectively classified into four types according to the US features, the corresponding positive predictive values (PPVs) were obtained. Clinical, imaging, and histopathological findings were reviewed. RESULTS: Among the 164 lesions, 39 (24%) were classified as type Ia, 14 (8%) as type Ib, 39 (24%) as type IIa, 19 (12%) as type IIb, 19 (12%) as type III, and 34 (21%) as type IV. The PPVs for malignancy were 21% for type Ia, 79% for type Ib, 10% for type IIa, 58% for type IIb, 16% for type III, and 21% for type IV. All NML lesions were classified as BI-RADS category 4a (type IIa), 4b (type Ia, III and IV) and 4c (type Ib and IIb) according to their PPVs. There was a significantly higher frequency of malignancy among lesions of type Ib and type IIb compared with the other types (P<0.01 for each). Lesions with associated calcifications, presence of abnormal axillary nodes, or a mammographic finding of suspected malignancy had a higher probability of malignancy (P<0.05 for each). CONCLUSION: US is useful in clarifying the indication for biopsy of NML lesions. The types of US classifications used in our study establish reliable references for the NML patterns when stratified according to the BI-RADS categories.

The outcome of a quality-controlled mammography screening program: experience from a population-based study in Taiwan.

BACKGROUND: A greater policy of emphasis on the early detection and treatment of breast cancer is prevalent among developed countries. To raise the screening performance with a potentially decreased mortality rate, it is crucial to evaluate and analyze the screening outcome after implementation. We report the clinical outcome of an 8-year nationwide mammography screening in Taiwan to help share our statistical information on breast screening worldwide, especially in Asia. METHODS: Taiwan has provided nationwide, free, biennial mammographic screening since 2004. A total of 2,392,789 consecutive screening mammography examinations were performed during this study period for women aged 50-69 years (2006-2009) and 45-69 years (from December 2009 onwards). The screening covers 33.2% of the target population in the most recent 2 years. The workload of every screening radiologist, the overall recall rate, positive predictive value (PPV1), cancer detection rate (CDR), cancer incidence rate (CIR) from the screening, 1-year interval cancer, sensitivity, and specificity of the screening mammography are calculated, and compared with the American College of Radiology (ACR) recommendation level and/or those of other screening mammographic series. RESULTS: The CDRs (%) and CIRs (%) increased from 3.94-4.08 and 4.80-5.04 to 4.71-5.04 and 5.71 after 2009, implying a high occurrence of breast cancer in the younger age group of 45-49 years. The recall rates (9.3-10.0%) in this review are within the ACR recommendation range (<10%) and the PPV1 has also reached the ACR recommended level (>5%) in the most recent 2 years. The improvement of the screening performance may be attributed to our peer auditing review and education program. The sensitivity of our screening mammography is slightly lower than that of the ACR recommended level (>85%), which is still comparable to the results of the Vermont area in the USA. Although the workload (screenees/screeners) for every radiologist each year has increased from 150 in 2004 to 1360 in 2012, it does not seem to worsen the quality outcome of this screening program. CONCLUSION: From the outcome review of this national mammography screening, there is still room to ameliorate our performance through comprehensive and continued education, to improve the competence of cancer detection and decrease false negative (FN) cases.

Underestimation of invasive lesions in patients with ductal carcinoma in situ of the breast diagnosed by ultrasound-guided biopsy: a comparison between patients with and without HER2/neu overexpression.

PURPOSE: To determine the rate of underestimation of ductal carcinoma in situ (DCIS) diagnosed at imaging-guided biopsy and to analyze its association with HER2/neu oncogene, an important biomarker in assessing the tumour aggressiveness and guiding hormone therapy for breast cancer. METHODS: We retrospectively reviewed 162 patients with DCIS diagnosed by imaging-guided core needle biopsy between January 2008 and March 2013. All of these patients received surgical excision, and in 25, the diagnosis was upgraded to invasive breast cancer. In this study, we examined the ultrasound, mammographic features and histopathological results for each patient, and compared these parameters between those with and without HER2/neu overexpression. RESULTS: Of the 162 DCIS lesions, 110 (67.9%) overexpressed HER2/neu. Nineteen patients with HER2/neu overexpressing DCIS (n=19/110, 17.3%) were upgraded after surgery to a diagnosis of invasive breast cancer. In this group, the upgrade rate was highest in patients with a dilated mammary duct pattern (42.1%, n=8/19, p=0.02) and the presence of abnormal axillary nodes (40.0%, n=12/30, p<0.01) at ultrasound and was significantly associated with comedo tumour type on pathology. CONCLUSIONS: Biopsy may underestimate the invasive component in DCIS patients. Sonographic findings of dilated mammary ducts and presence of abnormal axillary lymph nodes may help predicting the invasive components and possibly driving more targeted biopsy procedures.

Effects of quality assurance regulatory enforcement on performance of mammography systems: evidence from large-scale surveys in Taiwan.

OBJECTIVE: The Standards for Medical Exposure Quality Assurance in mammography systems were enacted on July 1, 2008, in Taiwan. This study aimed to evaluate the trends in performance of mammography units before and after the regulation started on the basis of annual on-site surveys from 2008 to 2010. MATERIALS AND METHODS: On-site measurements were conducted on 215, 205, and 209 mammography units in 2008, 2009, and 2010, respectively, which accounted for more than 95% of all units in Taiwan. Phantom image quality, average glandular dose (AGD), and half-value layer were evaluated on all systems. Processor conditions, compression conditions, radiation output, and computed radiography exposure indicators were assessed on units participating in mammography screening in 2008 and on all units in the later years. Evaluations of maximum compression force and automatic exposure control reproducibility were added into the protocol from 2009 onward. RESULTS: Mean phantom scores were improved significantly from 2008 to 2009 (11.63 ± 1.30 vs 12.31 ± 0.94, p < 0.05) and remained stable for 2010 (12.35 ± 0.87). Mean AGDs were 1.48 ± 0.47, 1.38 ± 0.41, and 1.37 ± 0.42 mGy over the 3 years, with a significant reduction from 2008 to 2009 (p < 0.05). For film-screen mammography systems, variations of sensitometric curves were greatly reduced in 2009 and 2010 when compared with 2008. Passing rates were increased after the regulation took effect in almost all aspects. CONCLUSION: Results from large-scale on-site surveys showed an overall improvement in performance after quality assurance in mammography was enforced in Taiwan.

Peer reviewing of screening mammography in Taiwan: its reliability and the improvement.

BACKGROUND: Early detection with screening mammography can potentially reduce breast cancer mortality rates. To achieve an efficient screening, a peer review system provides a compensatory double-check reviewing, will hopefully to prevent the omission of detectable lesions and reduce unnecessary recall. METHODS: In 2009, 4643 initial mammographic screenings reported by 74 screening radiologists had negative results with a recall rate of less than 5%. In the same year, 2538 initial positives screened by 18 screening radiologists had a recall rate higher than 15%. Those 7181 randomized screenings were evenly distributed for reassessment by 39 reviewing radiologists. The disagreement of assessments between the reviewers and screening radiologists was recorded. The differential rate was defined as the number of the disagreements divided by the number of audited films reviewed by a screening radiologist. The equality of the differential rates for each screening radiologists with negative and positive assessments was compared by a Chi-square test. The performance of the 39 auditors was measured by the Kendall's tau statistic. P values less than 0.05 were considered statistically significant. RESULTS: The mean differential rate for screening radiologists of negative assessments was 6.7% (P = 0.588), while 35.0% for positive assessments were significant (P < 0.001). The result indicated that most of the initial negative assessments reported by the screening radiologists were generally accepted by the reviewers but not the positive assessments. With respect to the 39 reviewers, there was no significant evidence for the association of the difference rates between negative and positive assessments. Nine reviewers were found to have their differential rate for negative and positive assessments larger than the average of the population. Eleven reviewers were found to have their differential rates smaller than the average for both. Thirteen reviewers had their differential rates smaller than the average for negative assessments but larger than the average for positive assessments. The opposite condition was found for six reviewers. The Kendall's tau statistic was 0.038 (P = 0.735). CONCLUSIONS: Reviewers usually agreed with the opinion of the initial screening doctors who reported negative findings. Therefore, a 5% recall rate as the lower range of reviewing negatives may be still too high. The recall rate of more than 15% was significantly related to improper interpretation, especially when the differential rate is 25% or higher, a warning to the underperforming screening radiologist is recommended. An ideal reviewer should interpret films independently. Reviewers with tendencies to be followers or contrarians should not be enrolled in the reviewing system.

Can missed breast cancer be recognized by regular peer auditing on screening mammography?

BACKGROUND: This study was conducted to investigate whether detectable missed breast cancers could be distinguished from truly false negative images in a mammographic screening by a regular peer auditing. METHODS: Between 2004 and 2007, a total of 311,193 free nationwide biennial mammographic screenings were performed for 50- to 69-year-old women in Taiwan. Retrospectively comparing the records in Taiwan's Cancer registry, 1283 cancers were detected (4.1 per 1000). Of the total, 176 (0.6 per 1000) initial mammographic negative assessments were reported to have cancers (128 traditional films and 48 laser-printed digital images). We selected 186 true negative films (138 traditional films and 48 laser-printed ones) as control group. These were seeded into 4815 films of 2008 images to be audited in 2009. Thirty-four auditors interpreted all the films in a single-blind, randomized, pair-control study. The performance of 34 auditors was analyzed by chi-square test. A p value of < 0.05 was considered significant. RESULTS: Eight (6 traditional and 2 digital films) of the 176 false negative films were not reported by the auditors (missing rate of 4.5%). Of this total, 87 false negatives were reassessed as positive, while 29 of the 186 true negatives were reassessed as positive, making the overall performance of the 34 auditors in interpreting the false negatives and true negatives a specificity of 84.4% and sensitivity of 51.8%. The specificity and sensitivity in traditional films and laser-printed films were 98.6% versus 43.8% and 41.8% versus 78.3%, respectively. Almost 42% of the traditional false negative films had positive reassessment by the auditors, showing a significant difference from the initial screeners (p < 0.001). The specificity of their reinterpretation of laser-printed films was obviously low. CONCLUSION: Almost 42% of the false negative traditional films were judged as missed cancers in this study. A peer auditing should reduce the probability of missed cancers.

Dietary intake of vitamin B(6) and risk of breast cancer in Taiwanese women.

BACKGROUND: B vitamins, including vitamin B(6), are coenzymes that are important for DNA integrity and stability. Deficiencies in B vitamins may promote tumor carcinogenesis. METHODS: We examined the association of dietary vitamin B(6) intake with overall breast cancer risk and breast cancers stratified by hormone receptor status. This case-control study included 391 breast cancer cases and 782 control subjects enrolled at the Tri-Service General Hospital in Taipei, Taiwan. Energy-adjusted intake of vitamin B(6) was derived from a food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: As compared with women in the lowest tertile, the multivariate-adjusted ORs for breast cancer among women in the second and highest tertiles of vitamin B(6) intake were 0.78 (95% CI, 0.64-2.52) and 0.64 (0.26-0.92), respectively. In addition, higher vitamin B(6) intake was associated with a significantly lower risk of developing ER-negative breast tumors. CONCLUSIONS: Our findings suggest that higher intake of vitamin B(6) is associated with a reduction in breast cancer risk, particularly ER-negative tumors.

Genetic variation in the genome-wide predicted estrogen response element-related sequences is associated with breast cancer development.

INTRODUCTION: Estrogen forms a complex with the estrogen receptor (ER) that binds to estrogen response elements (EREs) in the promoter region of estrogen-responsive genes, regulates their transcription, and consequently mediates physiological or tumorigenic effects. Thus, sequence variants in EREs have the potential to affect the estrogen-ER-ERE interaction. In this study, we examined the hypothesis that genetic variations of EREs are associated with breast cancer development. METHODS: This case-control study involved 815 patients of Asian descent with incident breast cancer and 821 healthy female controls. A total of 13,737 ERE sites in the whole genome predicted by a genome-wide computational algorithm were blasted with single-nucleotide polymorphism (SNP) sequences. Twenty-one SNPs located within 2,000 bp upstream or within introns 1 and 2 of putative genes and with a minor allele frequency greater than 5% were identified and genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility. RESULTS: A significant combined effect of rs12539530, an ERE SNP in intron 2 of NRCAM which codes for a cell adhesion molecule, and SNPs of ESR1, the gene coding for ER, on breast cancer risk was found. Interestingly, this combined effect was more significant in women who had experienced a longer period of lifetime estrogen exposure, supporting a hormonal etiology of this SNP in breast tumorigenesis. CONCLUSIONS: Our findings provide support for a role of genetic variation in ERE-ESR1 in determining susceptibility of breast cancer development.

Incidentally detected enhancing breast lesions on chest computed tomography.

OBJECTIVE: To evaluate the nature and imaging appearance of incidental enhancing breast lesions detected on a routine contrast-enhanced chest CT. MATERIALS AND METHODS: Twenty-three patients with incidental enhancing breast lesions on contrast-enhanced chest CT were retrospectively reviewed. The breast lesions were reviewed by unenhanced and enhanced CT, and evaluated by observing the shapes, margins, enhancement patterns and backgrounds of breast lesions. A histopathologic diagnosis or long-term follow-up served as reference standard. RESULTS: Sixteen (70%) patients had malignant breast lesions and seven (30%) had benign lesions. In 10 patients, the breast lesions were exclusively detected on contrast-enhanced CT. Using unenhanced CT, breast lesions with fibroglandular backgrounds were prone to be obscured (p < 0.001). Incidental primary breast cancer showed an non-significant trend of a higher percentage irregular margin (p = 0.056). All of the four incidental breast lesions with non-mass-like enhancement were proven to be malignant. CONCLUSION: Routine contrast-enhanced chest CT can reveal sufficient details to allow for the detection of unsuspected breast lesions, in which some cases may be proven as malignant. An irregular margin of incidental enhancing breast lesion can be considered a suggestive sign of malignancy.

Complex cystic lesions of the breast on ultrasonography: feature analysis and BI-RADS assessment.

PURPOSE: To analyze the features of breast complex cystic lesions at ultrasonography (US) and to determine appropriate Breast Imaging Reporting and Data System (BI-RADS) categories and management recommendations for these lesions based on US findings with pathologic correlation. MATERIALS AND METHODS: From July 2001 to June 2007, 152 consecutive pathologically proven complex cystic lesions on US were retrospectively reviewed. All lesions at US were evaluated for size, lesion characteristics, margins, and presence of abnormal axillary nodes. US features of lesions were classified into four types, and positive predictive values (PPVs) were calculated for each type. Clinical, imaging, and histopathological findings were reviewed. RESULTS: Of the 152 lesions based on US appearance, 36 (24%) were classified as type I, 49 (32%) as type II, 28 (18%) as type III, and 39 (26%) as type IV. The PPVs for malignancy in each type were 14% for type I, 16% for type II, 14% for type III, and 41% for type IV. There was a significantly higher frequency of malignancy among lesions of type IV compared with the other three types (16/39=41% vs 5/36=14%, p=0.0089; 16/39=41% vs 8/49=16%, p=0.0098; and 16/39=41% vs 4/28=14%, p=0.018 [Chi-squared test]). Lesions with maximum diameter equal to or larger than 20mm, not circumscribed margins, or a mammographic finding of suspected malignancy had a high probability of malignancy (p<0.05 for each). CONCLUSION: US is useful in evaluating the complex cystic lesions and in clarifying the indication for biopsy of these lesions. The four types of US classifications used in our study establish accepted benchmarks for these breast abnormalities when stratified according to BI-RADS categories.

Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case-control study in Taiwan.

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5'-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11-2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89-8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ's effects should be pursued in future investigations.

Diverse associations between ESR1 polymorphism and breast cancer development and progression.

PURPOSE: To test the hypothesis that polymorphisms of ESR1, the gene encoding estrogen receptor alpha (ERalpha), are associated with susceptibility, clinical phenotype, and progression of breast cancer. PATIENTS AND METHODS: A case-control study was done on 940 patients with incident breast cancer and 1,547 healthy female controls. Fifteen single-nucleotide polymorphisms (SNP) selected from chr6:152,170,379-152,466,100 (exons 1-8 of the ESR1 gene, excluding flanking sequences), reflecting major polymorphisms of this gene, were genotyped. Frequencies of SNPs were compared between cases and controls to identify SNPs associated with cancer susceptibility and between cases with different clinical phenotypes to determine the role of ESR1 polymorphism in cancer progression. RESULTS: SNPs located in one cluster in intron 1 and one haplotype, based on these SNPs, showed a significant association with breast cancer susceptibility. The tumorigenic contribution of these intron 1 SNPs was more obvious in combination with reproductive risk factors (P for interaction <0.05). One of these intron 1 SNPs was also significantly associated with low ERalpha expression in tumors. Interestingly, the same intron 1 SNPs showed a correlation with worse clinical phenotypes, including poor differentiation of tumor cells and a late stage. These intron 1 SNPs also showed a significant association with the 5-year breast cancer-specific survival rate of patients, but had opposite effects in ERalpha-negative and ERalpha-positive early-stage patients. CONCLUSIONS: Our findings provide support for diverse roles of ESR1 polymorphism in determining susceptibility in different stages of breast cancer. The differences between the important ESR1 SNPs identified in Chinese women in this study and those identified in studies on Western women with breast cancer suggest different roles of ERalpha in these two populations.

Adipocytokine resistin and breast cancer risk.

Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.

Ultrasonographic alterations associated with the dilatation of mammary ducts: feature analysis and BI-RADS assessment.

OBJECTIVE: The purpose of this study was to analyse the lesion characteristics and the patterns of dilated ducts on ultrasonography (US) to determine the appropriateness of the Breast Imaging Reporting and Data System (BI-RADS) categories. MATERIALS AND METHODS: From July 2001 to June 2006, 172 consecutive pathologically proved lesions with dilated ducts on US were reviewed retrospectively. All the lesions were classified into four types according to their US features, and in combination with the size, location, margins and number of lesions, the corresponding positive predictive values (PPVs) were obtained. RESULTS: Of the 172 lesions, 55 (32%) were classified as type I, 68 (40%) as type II, 14 (8%) as type III and 35 (20%) as type IV. The PPVs for malignancy were 9% for type I, 13% for type II, 43% for type III and 17% for type IV. There was a significantly higher frequency of malignancy among type III lesions than among type I (43% vs 9%, respectively, P = 0.002; chi (2) test) or type II lesions (43% vs 13%, respectively, P = 0.009; chi (2) test). Lesions with a nonsubareolar location and noncircumscribed margins had a high probability of malignancy (P < 0.001 and P = 0.03, respectively). CONCLUSION: The four types of US classifications used in our study establish reliable references for the dilated duct patterns when stratified according to BI-RADS categories, and they clarify the indications for biopsy of these lesions.