Search

Background: The aim of this study was to investigate whether the PAM-50-based 46-gene assay carries prognostic value for risk of local recurrence of breast cancer. Methods: The Austrian Breast and Colorectal Cancer Study Group (ABCSG) 8 RCT compared 5 years of tamoxifen with tamoxifen for 2 years followed by anastrozole for 3 years in postmenopausal women with endocrine receptor-positive breast cancer. This study included patients from the trial who had breast-conserving surgery for whom tumour blocks were available for PAM-50 analysis. Results: Tumour blocks from 1204 patients who had breast-conserving surgery were available for the PAM-50 analysis, and 1034 of these received radiotherapy. After a median follow-up of 10.8 years, 23 local events had been observed, corresponding to an overall local recurrence risk of 2.2 per cent. Univariable competing-risk analysis demonstrated that patients at low risk according to PAM-50 analysis (risk-of-recurrence (ROR) score less than 57) had a significantly lower incidence of local recurrence than those in the highrisk group at 5 years (0.1 (95 per cent c.i. 0 to 0.7) versus 2.2 (0.9 to 4.6) per cent respectively; subhazard ratio (SHR) 17.18, 95 per cent c.i. 2.06 to 142.88; P=0.009) and 10 years (0.9 (0.4 to 2.0) versus 3.8 (1.9 to 6.6) per cent; SHR 4.76, 1.72 to 13.17; P=0.003). Multivariable analyses that included ROR score, age, tumour size, nodal status, type of surgery, tumor grade, and trial-specific endocrine therapy confirmed that ROR score was an independent prognostic factor for risk of local recurrence. Analysis of the women randomized to radiotherapy or control after breast conservation showed that PAM-50 was not predictive of radiotherapy effect. Conclusion: PAM-50 can be used as a prognostic tool for local recurrence risk in postmenopausal women with hormone receptorpositive breast cancer treated with endocrine therapy. The test was not predictive for the benefit of radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: To identify which breast lesion descriptors in the ACR BI-RADS® MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T.Methods: 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS® classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS® descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference.Results: The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape (p < 0.001), irregular margin (p < 0.001), heterogeneous enhancement (p < 0.001), Type 3 enhancement kinetics (p = 0.02), increasing patient age (p = 0.02) and larger lesion size (p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape (p = 0.06), mass margin (p < 0.001), internal enhancement pattern (p = 0.03) and Type 3 enhancement kinetics (p = 0.06).Conclusion: The ACR BI-RADS® breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics.Key Points: • 3 Tesla breast MRI allows an accurate diagnosis of breast cancer • The BI-RADS® descriptors help provide a confident diagnosis • The shape, margin, enhancement pattern and kinetics are the most important features • An irregular shape and margin, heterogeneous enhancement and type-3 kinetics indicate malignancy. [ABSTRACT FROM AUTHOR]

We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65-74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75-84 years among the old-old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9-6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease-not TNBC-featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted. [ABSTRACT FROM AUTHOR]

Background: Seroma formation is the major morbidity nuisance after breast cancer surgery. It prolonges hospital stay and causes infections and wound healing problems. The aim of the study was to evaluate the impact of the vessel sealing device LigaSure™ on postoperative morbidity especially seroma formation. Methods: Between 2011 and 2012, data were retrospectively evaluated from 59 women with breast cancer who underwent axillary dissection at a university hospital. The Clavien Dindo Classification (CDC) was used to assess the severity of postoperative complications. Surgery was performed with LigaSure™ in 23 patients (39.0 %) compared with monopolar electrocautery in the control group. Results: A total of 36 patients (61.0 %) had breast conserving surgery, and 5 patients (8.5 %) underwent isolated axillary dissection. Morbidity-associated re-operations were reported in 5.1 %. Seroma rates were nearly twice as high in the control group compared with LigaSure™ patients ( p = 0.056). Hospital stay was shortened by 1 day using LigaSure™. The rate of punctures at the outpatient ward was half as high in the LigaSure™ cohort (21.7 vs. 41.7 %; p = 0.115). The frequency of aspirations (≤ 2 times) was lower in LigaSure™ patients. Despite this, the median puncture volume was higher (195 ml; IQR: 112.5-265 ml) in the LigaSure™ cohort as compared with the control group (100 ml; IQR: 60-180 ml). Overall, the CDC was significantly lower in the LigaSure™ group compared with the conventional cohort ( p = 0.038). Conclusions: The vessel sealing device LigaSure™ leads to a reduction of postoperative morbidity, hospital stay, and puncture frequency, which is desirable in terms of cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background:The aim of this study was to examine whether EndoPredict (EP), a novel genomic expression test, is effective in predicting local recurrence (LR)-free survival (LRFS) following surgery for breast cancer in postmenopausal women. In addition, we examined whether EP may help tailor local therapy in these patients.Methods:From January 1996 to June 2004, 3714 postmenopausal patients were randomly assigned to either tamoxifen or tamoxifen followed by anastrozole within the prospective ABCSG 8 trial. Using assay scores from EP, we classified breast tumour blocks as either low or high risk for recurrence.Results:Data were gathered from 1324 patients. The median follow-up was 72.3 months and the cumulative incidence of LR was 2.6% (0.4% per year). The risk of LR over a 10-year period among patients with high-risk lesions (n=683) was significantly higher (LRFS=91%) when compared with patients with low-risk lesions (n=641) (10-year LRFS=97.5%) (HR: 1.31 (1.16-1.48) P<0.005). The groups that received breast conservation surgery (BCT) and mastectomy (MX) had similar LR rates (P=0.879). Radiotherapy (RT) after BCT significantly improved LRFS in the cohorts predicted by EP to be low-risk for LR (received RT: n=436, 10-year LRFS 99.8%; did not receive RT: n=63, 10-year LRFS 83.6%, P<0.005).Conclusions:EndoPredict is an effective prognostic tool for predicting LRFS. Among postmenopausal, low-risk patients, EP does not appear to be useful for tailoring local therapy. [ABSTRACT FROM AUTHOR]

Background: Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations.Methods: We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness.Results: The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective.Conclusions: The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy. [ABSTRACT FROM AUTHOR]

Background:Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER+, HER2− early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations.Methods:We prospectively recruited 75 ER+, HER2− breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness.Results:The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective.Conclusions:The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to evaluate the clinical application of bilateral high spatial and temporal resolution dynamic contrast-enhanced magnetic resonance imaging (HR DCE-MRI) of the breast at 7 T.Methods: Following institutional review board approval 23 patients with a breast lesion (BIRADS 0, 4-5) were included in our prospective study. All patients underwent bilateral HR DCE-MRI of the breast at 7 T (spatial resolution of 0.7 mm(3) voxel size, temporal resolution of 14 s). Two experienced readers (r1, r2) and one less experienced reader (r3) independently assessed lesions according to BI-RADS®. Image quality, lesion conspicuity and artefacts were graded from 1 to 5. Sensitivity, specificity and diagnostic accuracy were assessed using histopathology as the standard of reference.Results: HR DCE-MRI at 7 T revealed 29 lesions in 23 patients (sensitivity 100 % (19/19); specificity of 90 % (9/10)) resulting in a diagnostic accuracy of 96.6 % (28/29) with an AUC of 0.95. Overall image quality was excellent in the majority of cases (27/29) and examinations were not hampered by artefacts. There was excellent inter-reader agreement for diagnosis and image quality parameters (κ = 0.89-1).Conclusion: Bilateral HR DCE-MRI of the breast at 7 T is feasible with excellent image quality in clinical practice and allows accurate breast cancer diagnosis.Key Points: • Dynamic contrast-enhanced 7-T MRI is being developed in several centres. • Bilateral high resolution DCE-MRI of the breast at 7 T is clinically applicable. • 7-T HR DCE-MRI of the breast provides excellent image quality. • 7-T HR DCE-MRI should detect breast cancer with high diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to evaluate the clinical application of bilateral high spatial and temporal resolution dynamic contrast-enhanced magnetic resonance imaging (HR DCE-MRI) of the breast at 7 T. Methods: Following institutional review board approval 23 patients with a breast lesion (BIRADS 0, 4-5) were included in our prospective study. All patients underwent bilateral HR DCE-MRI of the breast at 7 T (spatial resolution of 0.7 mm voxel size, temporal resolution of 14 s). Two experienced readers (r1, r2) and one less experienced reader (r3) independently assessed lesions according to BI-RADS®. Image quality, lesion conspicuity and artefacts were graded from 1 to 5. Sensitivity, specificity and diagnostic accuracy were assessed using histopathology as the standard of reference. Results: HR DCE-MRI at 7 T revealed 29 lesions in 23 patients (sensitivity 100 % (19/19); specificity of 90 % (9/10)) resulting in a diagnostic accuracy of 96.6 % (28/29) with an AUC of 0.95. Overall image quality was excellent in the majority of cases (27/29) and examinations were not hampered by artefacts. There was excellent inter-reader agreement for diagnosis and image quality parameters (κ = 0.89-1). Conclusion: Bilateral HR DCE-MRI of the breast at 7 T is feasible with excellent image quality in clinical practice and allows accurate breast cancer diagnosis. Key points: • Dynamic contrast-enhanced 7-T MRI is being developed in several centres. • Bilateral high resolution DCE-MRI of the breast at 7 T is clinically applicable. • 7-T HR DCE-MRI of the breast provides excellent image quality. • 7-T HR DCE-MRI should detect breast cancer with high diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Background: ER+/HER2- breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy.Methods: A total of 1702 postmenopausal ER+/HER2- breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis).Results: EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up.Conclusion: The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome. [ABSTRACT FROM AUTHOR]

Background:ER+/HER2− breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy.Methods:A total of 1702 postmenopausal ER+/HER2− breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary end point was distant metastasis (DM). Kaplan-Meier method and Cox regression analysis were used in an early (0-5 years) and late time interval (>5 years post diagnosis).Results:EP is a significant, independent, prognostic parameter in the early and late time interval. The expression levels of proliferative and ER signalling genes contribute differentially to the underlying biology of early and late DM. The EPclin stratified 64% of patients at risk after 5 years into a low-risk subgroup with an absolute 1.8% of late DM at 10 years of follow-up.Conclusion:The EP test provides additional prognostic information for the identification of early and late DM beyond what can be achieved by combining the commonly used clinical parameters. The EPclin reliably identified a subgroup of patients who have an excellent long-term prognosis after 5 years of endocrine therapy. The side effects of extended therapy should be weighed against this projected outcome. [ABSTRACT FROM AUTHOR]

Background:Body mass index (BMI) has an impact on survival outcome in patients treated with aromatase inhibitors (AIs). Obesity is associated with an increased body aromatisation and may be a cause of insufficient estradiol depletion.Methods:Sixty-eight postmenopausal oestrogen receptor-positive patients with early breast cancer were prospectively included in this study. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were analysed immediately in the clinical routine lab and in a dedicated central lab before (T1) and 3 months after start with aromatase inhibitors (T2).Results:A total of 40 patients were normal or overweight (non-obese: BMI 18.5-29.9 kg m−2) and 28 were obese (BMI30 kg m−2). Aromatase inhibitors significantly suppressed estradiol serum levels (T1: 19.5 pg ml−1, T2: 10.5 pg ml−1, P<0.01) and increased FSH serum levels (T1: 70.2 mIU ml−1, T2: 75.7 mIU ml−1, P<0.05). However, after 3 months of AI treatment, estradiol levels of obese patients were nonsignificantly higher compared with non-obese patients (12.5 pg ml−1 vs 9.0 pg ml−1, P=0.1). This difference was reflected by significantly lower FSH serum levels in obese compared with non-obese patients (65.5 mIU ml−1 vs 84.6 mIU ml−1, P<0.01). The significant effects of BMI on FSH serum levels could be detected both in the routine as well as in the dedicated central lab.Conclusion:Aromatase inhibitors are less efficient at suppressing estradiol serum levels in obese when compared with non-obese women. [ABSTRACT FROM AUTHOR]

Background:We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment.Methods:The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety.Results:In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P=0.02) and death (HR 0.45; P=0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P=0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P=0.68; distant recurrence-free survival HR 0.91; P=0.78; and OS HR 0.9; P=0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment (P=0.07).Conclusion:Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To develop and assess a combined reading for contrast-enhanced magnetic resonance (CE-MRI) and diffusion weighted imaging (DWI) adapted to the BI-RADS for multiparametric MRI of the breast at 3 T.Methods: A total of 247 patients with histopathologically verified breast lesions were included in this IRB-approved prospective study. All patients underwent CE-MR and DWI at 3 T. MRIs were classified according to BI-RADS and assessed for apparent diffusion coefficient (ADC) values. A reading method that adapted ADC thresholds to the assigned BI-RADS classification was developed. Sensitivity, specificity, diagnostic accuracy and the area under the curve were calculated. BI-RADS-adapted reading was compared with previously published reading methods in the same population. Inter- and intra-reader variability was assessed.Results: Sensitivity of BI-RADS-adapted reading was not different from the high sensitivity of CE-MRI (P = 0.4). BI-RADS-adapted reading maximised specificity (89.4 %), which was significantly higher compared with CE-MRI (P < 0.001). Previous reading methods did not perform as well as the BI-RADS method except for a logistic regression model. BI-RADS-adapted reading was more sensitive in non-mass-like enhancements (NMLE) and was more robust to inter- and intra-reader variability.Conclusion: Multiparametric 3-T MRI of the breast using a BI-RADS-adapted reading is fast, simple to use and significantly improves the diagnostic accuracy of breast MRI. KEYPOINTS : • Multiparametric breast 3-T MRI with BI-RADS-adapted reading improves diagnostic accuracy. • BI-RADS-adapted reading of CE-MRI and DWI is based on established reporting guidelines. • BI-RADS-adapted reading is fast and easy to use in routine clinical practice. • BI-RADS-adapted reading is robust to intra- and inter-reader variability. [ABSTRACT FROM AUTHOR]

Objective: To develop and assess a combined reading for contrast-enhanced magnetic resonance (CE-MRI) and diffusion weighted imaging (DWI) adapted to the BI-RADS for multiparametric MRI of the breast at 3 T. Methods: A total of 247 patients with histopathologically verified breast lesions were included in this IRB-approved prospective study. All patients underwent CE-MR and DWI at 3 T. MRIs were classified according to BI-RADS and assessed for apparent diffusion coefficient (ADC) values. A reading method that adapted ADC thresholds to the assigned BI-RADS classification was developed. Sensitivity, specificity, diagnostic accuracy and the area under the curve were calculated. BI-RADS-adapted reading was compared with previously published reading methods in the same population. Inter- and intra-reader variability was assessed. Results: Sensitivity of BI-RADS-adapted reading was not different from the high sensitivity of CE-MRI ( P = 0.4). BI-RADS-adapted reading maximised specificity (89.4 %), which was significantly higher compared with CE-MRI ( P < 0.001). Previous reading methods did not perform as well as the BI-RADS method except for a logistic regression model. BI-RADS-adapted reading was more sensitive in non-mass-like enhancements (NMLE) and was more robust to inter- and intra-reader variability. Conclusion: Multiparametric 3-T MRI of the breast using a BI-RADS-adapted reading is fast, simple to use and significantly improves the diagnostic accuracy of breast MRI. Keypoints: • Multiparametric breast 3-T MRI with BI-RADS-adapted reading improves diagnostic accuracy. • BI-RADS-adapted reading of CE-MRI and DWI is based on established reporting guidelines. • BI-RADS-adapted reading is fast and easy to use in routine clinical practice. • BI-RADS-adapted reading is robust to intra- and inter-reader variability. [ABSTRACT FROM AUTHOR]

Background:Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce.Methods:In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated.Results:Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted.Conclusion:Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria.Results: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients.Conclusion: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen. [ABSTRACT FROM AUTHOR]

Background:There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial.Methods:ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m−2), overweight (BMI=25-29.9 kg m−2), and obese (30 kg m−2) according to WHO criteria.Results:Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients.Conclusion:BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen. [ABSTRACT FROM AUTHOR]

Objective: To identify which breast lesion descriptors in the ACR BI-RADS® MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T. Methods: 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS® classification. Sensitivity, specificity and diagnostic accuracy were assessed. The effects of the BI-RADS® descriptors on sensitivity and specificity were evaluated. Data were analysed using logistic regression. Histopathological diagnoses were used as the standard of reference. Results: The sensitivity, specificity and diagnostic accuracy of breast MRI at 3 T was 99%, 81% and 93%, respectively. In univariate analysis, the final diagnosis of malignancy was positively associated with irregular shape ( p < 0.001), irregular margin ( p < 0.001), heterogeneous enhancement ( p < 0.001), Type 3 enhancement kinetics ( p = 0.02), increasing patient age ( p = 0.02) and larger lesion size ( p < 0.001). In multivariate analysis, significant associations with malignancy remained for mass shape ( p = 0.06), mass margin ( p < 0.001), internal enhancement pattern ( p = 0.03) and Type 3 enhancement kinetics ( p = 0.06). Conclusion: The ACR BI-RADS® breast lesion descriptors that are mostly strongly associated with breast cancer in breast MR imaging at 3 T are lesion shape, lesion margin, internal enhancement pattern and Type 3 enhancement kinetics. Key Points: • 3 Tesla breast MRI allows an accurate diagnosis of breast cancer • The BI-RADS® descriptors help provide a confident diagnosis • The shape, margin, enhancement pattern and kinetics are the most important features • An irregular shape and margin, heterogeneous enhancement and type-3 kinetics indicate malignancy [ABSTRACT FROM AUTHOR]

Background:Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010.Methods:Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test.Results:Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014).Conclusion:Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Background:Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.Methods:Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy.Results:Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012).Interpretation:This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS 70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy. [ABSTRACT FROM AUTHOR]

The objective of this study is to analyse local recurrence rates in patients receiving neoadjuvant chemotherapy (nCT) comparing mastecomized (MX) patients with those undergoing breast conserving therapy (BCT). Patients undergoing breast cancer surgery after nCT (3xCMF or 3-6xED) between 1995 and 2007 at our department were retrospectively analysed. The median follow up was 60 months for 308 patients. Patients who were downsized from MX to BCT with partial or complete response ( n = 104) had a similar local recurrence free survival (LRFS) compared to patients who did not experience successful downsizing ( n = 67) and finally undergoing MX (LRFS MX-BCT 81% vs. MX-MX 91%; P = 0.79). Uni- and multivariate analyses demonstrated that BCT itself was not an independent prognostic factor for a worse LRFS ( P = 0.07 and 0.14). After no pathologic change or progressive disease the risk of local recurrence was increased in patients undergoing BCT (MX-BCT; n = 6 LRFS 66%) compared with MX ( n = 44; LRFS 90%; P = 0.04). Overall survival in general was better for the BCT group ( n = 197) compared with MX group ( n = 111) regardless of clinical response (92% vs. 72%; P < 0.0001). Breast conservation, nodal negativity and low or medium grade histology were prognostic factors for an improved OS ( P = 0.02, 0.01, 0.004). In conclusion, our study suggests that BCT is oncologically safe after tumour downsizing by nCT in patients primarily scheduled for mastectomy. These patients, however, should not be treated with breast conservation in the absence of any proven response after nCT. [ABSTRACT FROM AUTHOR]

The article provides an answer to a question on the new developments on targeted therapies for breast cancer patients at the ASCO 2010 meeting.

Despite recent advances in the surgical and medical treatment of breast cancer, the number of patients dying from the disease is still high. In addition to improvements of early diagnosis and treatment, the overall mortality of breast cancer could be reduced by means of preventive intervention in both women with particularly normal and with high risk. Preventing the potentially deadly disease is presumably more effective than treatment, for life quality issues as well as for the economic perspective. Chemoprevention though is still a research field with results from large prevention trials being discussed controversially. For women with a defined increased risk for breast cancer, tamoxifen may be a choice for chemoprevention, balancing carefully benefits against risks. With promising results in adjuvant settings, aromatase inhibitors may deliver better prevention treatment options in the future, nevertheless, more research is needed to reliably predict risk on an individual basis in the future. [ABSTRACT FROM AUTHOR]

Despite recent advances in the surgical and medical treatment of breast cancer, the number of patients dying from the disease is still high. In addition to improvements of early diagnosis and treatment, the overall mortality of breast cancer could be reduced by means of preventive intervention in both women with particularly normal and with high risk. Preventing the potentially deadly disease is presumably more effective than treatment, for life quality issues as well as for the economic perspective. Chemoprevention though is still a research field with results from large prevention trials being discussed controversially. For women with a defined increased risk for breast cancer, tamoxifen may be a choice for chemoprevention, balancing carefully benefits against risks. With promising results in adjuvant settings, aromatase inhibitors may deliver better prevention treatment options in the future, nevertheless, more research is needed to reliably predict risk on an individual basis in the future. [ABSTRACT FROM AUTHOR]

During the San Antonio Breast Cancer Symposium 2007 some of the large prospective randomized trials reported failed to show clear-cut advantages of chemotherapeutic regimens that are considered to be more aggressive than standard therapy. Molecular profiles of breast cancer have allowed us to create standardized tools that make response prediction in several patient subsets possible. Although none of the new technology can be recommended for daily clinical practice, future trial design should implement some of the newly gained rationales at its best. Furthermore, tissue collection during the production of clinical trials should be considered mandatory in order to carry out translational research. Clearly, breast cancer research has moved from an era focusing on a treatment stratification largely determined by risk to an acknowledgement of disease heterogeneity requiring a prediction of response before therapy is assigned. [ABSTRACT FROM AUTHOR]

This report from the San Antonio Breast Cancer Symposium 2005 (SABCS 2005) outlines recent research pertaining to the origins of breast cancer and its translational, clinical and therapeutic consequences. In its first part, recent data concerning the origins of hormone receptors will be discussed. Presentations by 3 of the leading researchers in the field given during a minisymposium show that breast cancer is not a homogenous disease. In individual patients and within individual tumors, phenotypic and genotypic variety is present, posing a scientific challenge and the probable source of failure for the usually uniform treatment options used today. Furthermore, the characterization of different tumor cell subtypes and their respective origin may produce knowledge that can form the basis for new treatment modalities. Interestingly, tumor cells appear to maintain their principal molecular subtype throughout their transformation from earlier non-invasive and premalignant lesions, providing future potential for early detection and intervention. The molecular origin of different breast cancer subtypes may also affect epidemiologic data and therapeutic strategies. In the second part of this report, selected poster presentations on endocrine therapy, spectacular research about receptor signaling, molecular pathways and the biological implications of current treatments are summarized. [ABSTRACT FROM AUTHOR]

Aim Endorectal advancement flaps are an established treatment for high transsphincteric and suprasphincteric fistulae. The outcome of a repeat procedure in the case of flap breakdown and fistula recurrence remains unclear. The aim of the study was to analyse the outcome of repeat endorectal advancement flaps. Methods We retrospectively analysed patients with a repeat endorectal advancement flap procedure after flap breakdown and recurrence of fistula-in-ano of cryptoglandular origin who had been treated in our unit between 1994 and 2010. Results In all, 97 patients underwent an endorectal advancement flap procedure for fistula-in-ano and, of these, nine patients (five men, four women, 9.3%) subsequently underwent a repeat procedure due to flap breakdown. Median age was 40 years (range 25-60). Median follow-up time was 85 months (range 26-136). Seven full-thickness and two mucosal flap repeat procedures were performed because of eight transsphincteric and one suprasphincteric fistulae. The repeat procedure was successful in seven (78%) patients. In one of the two patients with repeat flap failure, a third flap procedure failed again. Disturbances of postoperative faecal incontinence were observed in five (55%) patients. Overall, the median postoperative Vaizey faecal incontinence score was 1 (range 0-4). Conclusion Repeat endorectal advancement flap procedures are feasible and associated with a low recurrence rate and mild postoperative faecal incontinence. Therefore, a repeat procedure is a viable option in the case of a flap breakdown and fistula recurrence. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy among women worldwide, and a quarter of all breast cancers are diagnosed in premenopausal women. Adjuvant chemotherapy is well established as the therapy of choice for hormone receptor-negative breast cancers. Historically, ovarian ablation substantially inhibited the progression of hormone-responsive breast cancer. Current adjuvant treatment options for premenopausal patients with hormone receptor-positive breast cancer include endocrine therapy and chemotherapy. Pharmacologic ovarian suppression alone has limited efficacy in the adjuvant setting, but it offers good clinical outcomes when combined with tamoxifen or chemotherapy. In recent years, aromatase inhibitors (AIs) have become the endocrine therapy of choice in postmenopausal women with hormone-responsive breast cancer, but their efficacy in the premenopausal setting is yet to be established. However, in a large, phase III randomized study (Austrian Breast and Colorectal Cancer Study Group Trial 12) that matured earlier this year, the combination of ovarian suppression and AI, anastrozole, did not show superior efficacy compared with ovarian suppression plus tamoxifen, but was associated with fewer serious adverse effects in premenopausal women with early stage hormone-responsive breast cancer. Data from ongoing and future trials will help to further define the role of ovarian suppression and AIs in the adjuvant setting for premenopausal breast cancer. [ABSTRACT FROM PUBLISHER]