Effects of a pre-visit educational website on information recall and needs fulfilment in breast cancer genetic counselling, a randomized controlled trial

Introduction

Pre-visit education which helps counselees to prepare for their first visit for breast cancer genetic counseling might enhance information recall and needs fulfilment. This study assessed the effects of a pre-visit website with tailored information and question prompt sheet (QPS), named E-info gene^ca.

Methods

A total of 197 counselees were randomized to receive usual care (UC) or UC plus E-info gene^ca. All counselees completed a pre- and post-visit questionnaire and visits were videotaped. We studied effects on counselees' information recall, knowledge about breast cancer and heredity, fulfillment of needs, risk perception alignment, anxiety and perceived personal control, using multilevel regression analyses.

Results

Intent-to-treat analysis showed that counselees in the intervention group (n = 103) had higher levels of recall of information from the consultation (?? = .32; confidence interval (CI): .04 to .60; P = .02; d = .17) and post-visit knowledge of breast cancer and heredity (?? = .30; CI: .03 to .57; P = .03) than counselees in the UC group (n = 94). Also, intervention group counselees reported better fulfilment of information needs (?? = .31; CI: .03 to .60; P = .03). The effects of the intervention were strongest for those counselees who did not receive an indication for DNA testing. Their recall scores showed a larger increase (?? = .95; CI: .32 to 1.59; P = .003; d = .30) and their anxiety levels dropped more in the intervention compared to the UC group (?? = -.60; CI: -1.12 to -.09; P = .02). No intervention effects were found after the first visit on risk perception alignment or perceived personal control.

Conclusions

This study shows that pre-counseling education, using tailored information technology, leads to more effective first visits for breast cancer genetic counseling, in particular for counselees who received no indication for DNA testing and, therefore, had no indication for a second visit. Future study should focus on the effects of a pre-visit website on the outcomes after a complete series of visits.

Trial registration

Dutch Trial Register ISRCTN82643064.     

Invasive breast cancers detected by screening mammography: A detailed comparison of computer‐aided detection‐assisted single reading and double reading

To compare double reading plus arbitration for discordance, (currently best practice, (BP)) with computer‐aided‐detection (CAD)‐assisted single reading (CAD‐R) for detection of invasive cancers detected within BreastScreen Australia. Secondarily, to examine characteristics of cancers detected/rejected using each method. Mammograms of 157 randomly selected double‐read invasive cancers were mixed 1:9 with normal cancers (total 1569), all detected in a BreastScreen service. Cancers were detected by two readers or one reader (C2 and C1 cancers, ratio 70:30%) in the program. The 1569 film‐screen mammograms were read by two radiologists (reader A (RA) and reader B(RB)), with findings recorded before and after CAD. Discordant findings with BP were resolved by arbitration. We compared CAD‐assisted reading (CAD‐RA, CAD‐RB) with BP, and CAD and arbitration contribution to findings. We correlated cancer size, sensitivity and mammographic density with detection methods. BP sensitivity 90.4% compared with CAD‐RA sensitivity 86.6% (P = 0.12) and CAD‐RB 94.3% (P = 0.14). CAD‐RB specificity was less than BP (P = 0.01). CAD sensitivity was 93%, but readers rejected most positive CAD prompts. After CAD, reader's sensitivity increased 1.9% and specificity dropped 0.2% and 0.8%. Arbitration decreased specificity 4.7%. Receiving operator curves analysis demonstrated BP accuracy better than CAD‐RA, borderline significance (P = 0.07), but not CAD‐RB. Secondarily, cancer size was similar for BP and CAD‐R. Cancers recalled after arbitration (P = 0.01) and CAD‐R (P = 0.10) were smaller. No difference in cancer size or sensitivity between reading methods was found with increasing breast density. CAD‐R and BP sensitivity and cancer detection size were not significantly different. CAD‐R specificity was significantly lower for one reader.     

The expression and clinical significance of β-catenin and colorectal cancer stem cells marker EpCAMhigh/CD44+ in colorectal cancer

Objective

The aim of the study was to explore the role of Wnt/β-catenin signalling pathway in the maintenance, invasion and metastasis of colorectal cancer stem cells.

Methods

Double immunohistochemical staining was used to detect the expression of EpCAM^high/CD44⁺ which is regarded as the marker of colorectal cancer stem cells in 80 cases of colorectal cancer and their corresponding liver metastases. The SP method of immunohistochemistry was used to detect the expression of the key protein β-catenin in the Wnt pathway in these tissue. The expression and correlation of β-catenin and EpCAM^high/CD44⁺ in colorectal cancer were analyzed and their role on the biological behavior of colorectal cancer was explored.

Results

The abnormal expression of β-catenin was significantly higher in colorectal cancer than in the paraneoplastic normal intestinal mucosa [55% (44/80) vs 10% (2/20), P < 0.05]. The positive expression of EpCAM^high/CD44⁺ was significantly higher in colorectal cancer than in the paraneoplastic normal intestinal mucosa [66.25% (53/80) vs 0% (0/20), P < 0.05]. In the 80 cases of colorectal cancer, the abnormal expression of β-catenin has no correlation with gender (P = 0.079), age (P = 0.416) and the magnitude (P = 0.816) of the tumor (P > 0.05), but it was significantly correlated with degree of differentiation (P = 0.001), depth of invasion (P = 0.001), clinical stage (P = 0.000) and metastasis (P = 0.000). In the colorectal cancer, the expression of EpCAM^high/CD44⁺ cells has no correlation with gender (P = 0.934) and the magnitude (P = 0.160) of the tumor (P > 0.05), but was significantly correlated with age (P = 0.021), degree of differentiation (P = 0.013), depth of invasion (P = 0.000), clinical stage (P = 0.000) and metastasis (P = 0.000). In the corresponding liver metastases, we could also detecte EpCAM^high/CD44⁺ cells. In cases with abnormal expression of β-catenin, the positive expression rate of EpCAM^high/CD44⁺ was significantly higher than those with normal expression of β-catenin (84.1% vs 44.4%), and the difference was statistically significant (P < 0.05).

Conclusion

The abnormal activation of Wnt/β-catenin signalling pathway may prompt the abnormal proliferation of the colorectal cancer stem cells, which leads to the recurrence and metastasis of the cancer.     

Cost-effectiveness analysis for breast cancer screening: double reading versus single + CAD reading

Background

Computer-aided detection (CAD) increases breast cancer detection, but its cost-effectiveness is unknown for breast cancer screening in Japan. We aimed to determine whether screening mammography diagnosed by one physician using CAD is cost-effective when compared with the standard double reading by two physicians.

Methods

We established our model with a decision tree and Markov model concept based on feasible screening and clinical pathways, combined with prognosis of the health state transition of breast cancer. Cost-effectiveness analysis between double reading by two readers and single reading with CAD by one reader was performed from a social perspective in terms of the expected cost, life expectancy and incremental cost-effectiveness ratio (ICER). The hypothetical population comprised 50-year-old female breast cancer screening examinees. Only direct medical costs related to breast cancer screening and treatment were considered. One simulation cycle was 2 years, and the annual discount rate was 3 %. Sensitivity analysis was performed to evaluate the robustness of the model and input data.

Results

Single reading with CAD increased expected costs by 2,704 yen and extended life expectancy by 0.0087 years compared with double reading. The ICER was 310,805 yen per life year gained, which is below the threshold. Sensitivity analysis showed that the sensitivity and specificity of CAD and the number of breast cancer screening examinees greatly affected the results.

Conclusions

Single reading using CAD in mammography screening is more cost-effective than double reading, although the results are highly sensitive to the sensitivity and specificity of CAD and the numbers of examinees.     

The clinical significance evaluation of serum β2-microglobulin for thyroid cancer patients

Objective

The aim of this study was to investigate the clinical value and relevance on the serum β₂-microglobulin (β₂-MG) of patients with thyroid cancer.

Methods

One thousand and two normal cases, 95 thyroid cancer patients and 243 nodular goiter patients were selected to measure serum β₂-MG levels using double-antibody sandwich enzyme-linked immunosorbent assay (ELISA).

Results

The positive rate of 7.78% in normal population (78/1002) and 31.57% in thyroid cancer patients (30/95). There were significant differences between the normal population and thyroid cancer patients (χ ² = 55.352; P = 0.000). The positive rate of 7.81% in nodular goiter patients (19/243) and there were no significant differences between the normal population and nodular goiter patients (χ ² = 0.0004; P = 0.986), but significant differences between nodular goiter patients and thyroid cancer patients (χ ² = 31.106; P = 0.000). Meanwhile, the significant difference of the positive rate existed in between the various pathological types of thyroid cancer (χ ² = 10.015; P = 0.007), anaplastic thyroid cancer patients with the highest positive rate and The significant difference was found between the positive lymph node metastasis groups and negative lymph node metastasis groups (χ ² = 4.441; P = 0.035), the presence of distant metastasis group and absence of distant metastasis group (χ ² = 9.795; P = 0.002).

Conclusion

Serum β₂-MG levels and prognosis of thyroid cancer patients was negatively correlated. It showed important clinical value to detect the level of β₂-MG in the early diagnosis, prognosis and the clinical observation for thyroid cancer patients.     

肥胖乳腺癌患者的临床特征及预后的回顾性研究(英文)

Objective:The aim of our study was to investigate the prognosis of obese breast cancer patients.Methods:This study was conducted on a total of 317 breast cancer patients who were histopathologically and clinically diagnosed at the General Hospital of Shenyang Military Region(China)from 2004 to 2006.Clinical data including height,weight,age at diagnosis,tumor size,lymph node status,menopausal status,family history of cancer and hormone receptor status were collected.Log-rank test was performed to compare the disease free survival(DFS)and overall survival(OS).Cox proportional hazards regression analysis was conducted to make multivariate analysis.The Chi square test was used to compare the clinical features among normal weight group,overweight group,and obese group.Results:Obesity was an independent prognostic factor for DFS(P=0.022)and OS(P=0.032)in breast cancer patients.In the stratified analysis based on the hormone receptor status,obesity was independently associated with OS in patients with negative ER/PR(P=0.002),but such association was not observed in patients with positive hormone receptors.Obesity was also associated with lymph node status(P=0.001)and smoking(P=0.009).Conclusion:Obesity is associated with poor DFS and OS in patients with breast cancer.Therefore,maintaining normal weight may benefit breast cancer patients.     

Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer

Introduction

Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall.

Methods

A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome.

Results

Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics.

Conclusion

Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening.     

408例70岁以上老年肺癌患者的预后因素分析

Objective

The incidence and mortality of lung cancer in people over 70 years were increased in the past 10 years. We defined age 70 years as boundary line of the elderly patients in lung cancer and analyzed and identified the factors affecting prognosis.

Methods

A retrospective study had enrolled 408 cases of lung cancer aged over 70 years old and SPSS13.0 software was used in univariate analysis and COX regression analysis to analyze factors affecting prognosis, such as gender, age, complications, symptoms, pathological type, clinical stage, effusion, surgery, radiotherapy, chemotherapy and so on.

Results

In univariate analysis, symptoms, stage, effusion, surgery, chemotherapy and chemotherapy cycles showed affecting prognosis significantly. In COX regression analysis, it showed that clinical stage (P = 0.000), surgery (P = 0.013), chemotherapy cycles (P = 0.001) were independent prognostic factors.

Conclusion

Elderly lung cancer patients could be benefit from surgery and adjuvant chemotherapy while early stage. At late stage, their survival time may be prolonged when receive chemotherapy at least 4 cycles. Single-agent chemotherapy would be a good choice for elderly lung cancer. Effusion, particularly, pericardial effusion significantly influenced the prognosis, so that it should be effectively controlled.     

Breast cancer in association with thyroid disorders

Background

The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease.

Methods

Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals.

Results

The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively).

Conclusion

Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.     

Mortalin is a prognostic factor of gastric cancer with normal p53 function

Background

Mortalin is a heat-non-inducible member of the heat shock protein 70 family. Mortalin binds to p53 and prevents p53 from entering the nucleus. To understand the significance of mortalin in gastric cancer, we investigated the expression of mortalin and p53.

Methods

Expression of mortalin and p53 was examined by immunohistochemical staining of 182 clinical samples of gastric cancer.

Results

Mortalin-positive and aberrant p53-positive tumors were found in 75.2 and 49.5 % of cases, respectively. Mortalin-positive tumors were deeper in invasion and had more lymph node and liver metastases compared with mortalin-negative tumors (P < 0.01, P < 0.05, respectively). Mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.035). Moreover, in tumors with normal p53 function, mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (P = 0.017).

Conclusions

Mortalin has a great impact on gastric cancer with normal p53. Therefore, mortalin is a target molecule for treatment of gastric cancer, as well as a promising prognostic factor, especially in tumors with normal p53.     

High expression of focal adhesion kinase (p125<Superscript>FAK</Superscript>) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

Introduction

Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy.

Methods

We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis.

Results

Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01).

Conclusions

Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src.

     

Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)

Objective: To examine the expressions of osteopontin (OPN), αVβ3 and Pim‐1 in non‐small cell lung cancer (NSCLC), and investigate their potential pathogenic roles in the development of NSCLC. Methods: Immunohistochemistry was used to examine the expressions of OPN, αVβ3 and Pim‐1 in cohort (136 cases) of NSCLC samples and their adjacent normal lung tissue specimens. Statistical analysis was performed to evaluate the relationships among expressions of OPN, αVβ3 and Pim‐1 and their associations with patients clinico‐pathological parameters. Results: The expressions of OPN and Pim‐1 were predominantly observed in cytoplasm. The expression of αVβ 3 was mostly detected in cytoplasm and/or membrane. In NSCLC samples, the positive rates of OPN, αVβ3 and Pim‐1 expressions were 68.4% (93/136), 77.2% (105/136) and 57.4% (78/136), respectively. In normal lung tissues, in contrast, the positive rates of OPN, αVβ3 and Pim‐1 were 24.0% (12/50), 26.0% (13/50) and 16.0% (8/50), respectively. There were significant differences of the positive expression rates of OPN, αVβ3 and Pim‐1 between NSCLCs samples and normal lung tissues (P<0.01). In addition, the positive expression of OPN, α Vβ3 and Pim‐1 in NSCLCs samples was significantly associated with increased pathological grade, lymph node metastasis and advanced clinical stage (P<0.01), and they were independent of other clinicopathological parameters (P>0.05). Furthermore, a significantly positive correlation between the expression of OPN and αVβ3 (r=0.38, P<0.01), OPN and Pim‐1 (r=0.37, P<0.01), or αVβ3 and Pim‐1 (r=0.20, P<0.05) was evaluated in our NSCLC cohort. Conclusion: OPN, αVβ3 and Pim‐1 proteins are frequently overexpressed in NSCLC, and they may play important roles in the development and/or progression of NSCLC.     

Cervical stromal involvement can predict survival in advanced endometrial carcinoma: a review of 67 patients

Purpose

To assess clinical, surgical and pathologic variables in survival of advanced endometrial cancer.

Methods

Sixty-seven advanced-stage (stages III and IV according to FIGO 2009) endometrial cancer cases were evaluated retrospectively. The effects on survival of age, histologic subtype, stage, grade, myometrial invasion, optimal cytoreduction, parity and cervical involvement were analyzed.

Results

Cervical involvement (P = 0.033) and nulliparity (P = 0.042) were worsening features in terms of survival. In 56 cases (83.5%) optimal cytoreduction could be achieved and survival was significantly longer in this group than the group who were not optimally cytoreduced (mean 30.4 vs. 9.6 months) (P < 0.01). Depth of myometrial invasion, histologic type of tumor, stage, grade, and age younger or older than 60 years were not found to be related to survival. Neither adjuvant therapy type nor their combination were superior to each other for improving survival.

Conclusions

Cervical stromal involvement is a poor prognostic factor in cases of advanced endometrial carcinoma. Further studies are required to describe the effect of different surgical approaches such as radical hysterectomy on survival in the presence of cervical stromal invasion.     

原发性乳腺癌患者治疗前血清TPS水平与预后之间的关系(英文)

Objective: The aim of this study was to explore the correlation of pretreatment serum tissue polypeptide specific antigen (TPS) with prognosis in primary breast cancer. Methods: A total of 361 patients with grades I-III breast cancer had been followed up from January 2001 to February 2011. Serumal TPS level was measured by enzyme-linked immunosorbent assays (ELISA). Univariate and multivariate analyses were used to investigate associations between pretreatment TPS level and clinicopathological parameters and patient outcomes. Results: First, at the univariate analysis, the expression of TPS was related with some clinicopathological traditional prognostic factors such as tumor size (P = 0.030), histologic grade (P = 0.001) and lymph node status (P = 0.008). Second, overall survival were significantly shorter among patients with elevated pretreatment serum TPS (P = 0.038). However, finally, multivariate Cox regression indicated that the level of pretreatment serum TPS was not an independent prognostic parameter for overall survival in primarily breast cancer patients (P > 0.05). Conclusion: The expression of pretreatment serum TPS is closely correlated with clinicopathology parameters and overall survival of patients with primarily breast cancer, but its level has no independent prognostic value.     

白细胞介素-18基因607和137多态性在前列腺癌临床特性的影响(英文)

Objective: The aim of this study was to determine whether the presence of IL-18 polymorphisms -137 G/C and -607 A/C was associated with grade, clinical stage, and survival in patients with prostate cancer. Methods: The study cohort included 126 patients with prostate cancer. Control group consisted of 125 samples from Chinese population. Genomic DNA was extracted from EDTA-anticoagulated peripheral blood leukocytes by the salting-out method. The genotyping of the two IL-18 polymorphisms was performed using predesigned TaqMan SNP Genotyping Assays. Results: The studied IL-18 gene polymorphisms did not influence susceptibility to prostate cancer in the analyzed group of patients (IL-18-607, P = 0.342; IL-18-137 P = 0.715) but may contribute to disease onset and aggressiveness. IL-18-607 CC genotype was significantly associated with higher tumor grade (P = 0.025) and stage (P = 0.001). IL-18-137 GG genotype was correlated with higher tumor grade (P = 0.018) and stage (P = 0.007). The Cox proportional hazard model showed that tuumor grade and stage grouping were independent prognostic factors but IL-18 polymorphism was not. Polymorphism variants in the IL-18 gene (IL-18-607 and IL-18-137) may be associated with a worse prognosis for prostate cancer. Conclusion: High levels of IL-18 production may play a major role in the growth, invasion and metastasis of prostate cancer.     

Prognostic implications of EGFR and HER-2 alteration assessed by immunohistochemistry and silver in situ hybridization in gastric cancer patients following curative resection

Background

The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection.

Patients and methods

In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I–III gastric cancer patients who underwent curative surgery.

Results

Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P < 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P < 0.001) and intestinal type (P = 0.002).

Conclusion

HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.     

Assessment of a fully automated,high-throughput mammographic density measurement tool for use with processed digital mammograms

Purpose

The ImageJ model is a recently developed automated breast density measurement tool based on analysis of Cumulus outcomes. It has been validated on digitized film-screen mammograms. In this study, the ImageJ model was assessed on processed full-field digital mammograms and correlated with the Breast Imaging Reporting and Data System (BI-RADS) density classification. Also, the association with breast cancer risk factors is observed.

Methods

Women with mammographies between 2001 and 2011 at the University Medical Center Utrecht, The Netherlands were included. We composed a training set, read with Cumulus, for building the ImageJ model [n = 100 women, 331 images; craniocaudal (CC) and mediolateral oblique (MLO) views, left and right] and a validation set for model assessment and correlation with the BI-RADS classification [n = 530 women, 1,977 images; average of available CC and MLO views, left and right]. Pearson product-moment correlation coefficient was used to compare Cumulus with ImageJ, Spearman correlation coefficient for ImageJ with BI-RADS density, and generalized linear models for association with breast cancer risk factors.

Results

The correlation between ImageJ and Cumulus in the training set was 0.90 [95 % confidence interval (CI) 0.86–0.93]. After application to the validation set, we observed a high correlation between ImageJ and the BI-RADS readings (Spearman r = 0.86, 95 % CI 0.84–0.88). Women with higher density were significantly younger, more often premenopausal, had lower parity, more often a benign breast lesion or family history of breast cancer.

Conclusions

The ImageJ model can be used on processed digital mammograms. The measurements strongly correlate with Cumulus, the BI-RADS density classification, and breast cancer risk factors.     

Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study

Introduction

Phytoestrogens are a group of compounds found in plants that structurally resemble the hormone oestradiol, and thus have the potential to act as oestrogen agonists or antagonists. Their potential effects may alter the risk of breast cancer, but only a limited range of phytoestrogens has been examined in prospective cohort studies.

Methods

Serum and urine samples from 237 incident breast cancer cases and 952 control individuals (aged 45 to 75 years) in the European Prospective into Cancer-Norfolk cohort were analysed for seven phytoestrogens (daidzein, enterodiol, enterolactone, genistein, glycitein, o-desmethylangolensin, and equol) using liquid chromatography/mass spectrometry. Data on participants' diet, demographics, anthropometrics, and medical history were collected upon recruitment. All models were adjusted for weight, fat and energy intake, family history of breast cancer, social class, analytical batch, and factors related to oestrogen exposure.

Results

Urinary or serum phytoestrogens were not associated with protection from breast cancer in the European Prospective into Cancer-Norfolk cohort. Breast cancer risk was marginally increased with higher levels of total urinary isoflavones (odds ratio = 1.08 (95% confidence interval = 1.00 to 1.16), P = 0.055); among those with oestrogen receptor-positive tumours, the risk of breast cancer was increased with higher levels of urinary equol (odds ratio = 1.07 (95% confidence interval = 1.01 to 1.12), P = 0.013).

Conclusion

There was limited evidence of an association between phytoestrogen biomarkers and breast cancer risk in the present study. There was no indication of decreased likelihood of breast cancer with higher levels of phytoestrogen biomarkers, but the observation that some phytoestrogen biomarkers may be associated with greater risk of breast cancer warrants further study with greater statistical power.     

Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases

Introduction

Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer.

Methods

We have investigated the correlations between disease characteristics and the patient genotypes of these SNPs in an unselected prospective cohort of 1,267 consecutive patients with primary breast cancer.

Results

Heterozygote carriers and minor allele homozygote carriers for SNP rs889312 in the MAP3K1 gene were less likely to be lymph node positive at breast cancer diagnosis (P = 0.044) relative to major allele homozygote carriers. Heterozygote carriers and minor allele homozygote carriers for SNP rs3803662 near the TNCR9 gene were more likely to be diagnosed before the age of 60 years (P = 0.025) relative to major allele homozygote carriers. We also noted a correlation between the number of minor alleles of rs2981582 in FGFR2 and the average number of first-degree and second-degree relatives with breast cancer and/or ovarian cancer (P = 0.05). All other disease characteristics, including tumour size and grade, and oestrogen or progesterone receptor status, were not significantly associated with any of these variants.

Conclusion

Some recently discovered genomic variants associated with a mildly increased risk of breast cancer are also associated with breast cancer characteristics or family history of breast cancer and ovarian cancer. These findings provide interesting new clues for further research on these low-risk susceptibility alleles.