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PDF file - 182K, Supplemental Figure 1. B cells activated with IL-21 and anti-BCR secrete enzymatically active granzyme B. Supplemental Figure 2. Interleukin 21 in the absence of B cells does not suppress T cell proliferation. Supplemental Figure 3. GrB-secreting B cells do not induce apoptosis in T cells. Supplemental Figure 4. IL-10, CD25 and IDO are expressed on IL-21-induced GrB+ Breg, but not on GrB- B cells. Supplemental Figure 5. IL-2 retitration has no significant effect on the suppression of CD4+ T cell proliferation by GrB-secreting B cells. Supplemental Figure 6. IL-21-induced GrB secretion by B cells depends on TLR7 and TLR9 signaling. Supplemental Figure 7. B cells in the microenvironment of solid tumors sporadically express IL-10.

MOV file - 3136K, Supplemental Video 1. B cells transfer active GrB to T cells.

Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project [1]. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell’s c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p &lt, 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3), intermediate risk: HR = 5.0, 95%CI.(3.6–6.9), high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p &lt, 0.001, NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.

ZusammenfassungDie AWMF und ihre Fachgesellschaften nehmen eine zunehmende Dominanz betriebswirtschaftlicher Ziele im stationären Gesundheitssektor wahr, die sich negativ auf die Patientenversorgung auswirken. Während eine angemessene, effiziente und gerechte Mittelverwendung geboten ist, belastet „Ökonomisierung“ Ärzte und Pflegende sowie die weiteren Gesundheitsberufe.Die AWMF hat zusammen mit Fachgesellschaftsvertretern Ursachen analysiert und Maßnahmen für eine wissenschaftliche, patientenzentrierte und ressourcenbewusste Medizin erarbeitet. Es bestehen Fehlanreize durch Vergütung, Zahl und Ausstattung von Krankenhäusern bzw. Fachabteilungen und deren Grundfinanzierung. Maßnahmen werden für die Patient–Arzt-Ebene, das Krankenhausmanagement, die Planung sowie Finanzierung von Krankenhäusern einschließlich der Vergütung stationärer Leistungen vorgeschlagen. Dabei bedarf es der gemeinsamen Anstrengung aller Akteure, um den Patienten und seine Gesundheit wieder in den Mittelpunkt zu stellen.

Background This study examined the association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer. Patients and methods In the prospective multicenter cohort study BRENDA II, patients aged ≥65 years with primary breast cancer were sampled over a period of 4 years (2009-2012). A multiprofessional team (tumor board) discussed recommendation for adjuvant chemotherapy according to the German S3 guideline. Cognitive impairment was screened by the clock-drawing test (CDT) prior to adjuvant treatment. Results Two hundred and sixty-three patients were included in the study and CDT data were available for 193 patients. Thirty-one percent of the patients had cognitive impairment with different degree of severity. In high-risk patients (n = 61) tumor board recommendation in favor of chemotherapy was 90% and in intermediate-risk patients (n = 170) 27%. Not receiving recommendation for chemotherapy in spite of guideline recommendation was more frequent in patients with cognitive impairment (67%) vs patients without cognitive impairment (46%) with P = 0.02 (OR 2.4, 95% confidence interval (CI) 1.2-4.9). Age, education, migration background and comorbidities were not associated with chemotherapy recommendation by the tumor board among cognitively impaired patients. Once the tumor board had recommended chemotherapy, application of chemotherapy was similar in both groups of patients with or without cognitive impairment. Conclusion Almost one third of older patients with breast cancer are affected by cognitive impairment prior to adjuvant treatment. In these patients, cognitive impairment was associated with tumor board decision against chemotherapy in spite of a positive guideline recommendation.

Background Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival. Methods We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming. Results The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p

Certified multi-disciplinary breast cancer centres (CBCs) have been established worldwide. Development of CBCs, guideline-adherent systemic therapy and surgical management should now show an impact on outcomes. This analysis aimed to investigate whether guideline adherence (GA) rates, relapse-free survival (RFS) and overall survival (OS) have significantly improved at CBCs compared to the pre-certification period.8323 patients with primary breast cancer were treated in 17 German CBCs, which had been certified between 2003 and 2007 [2003 (n = 1), 2004 (n = 6), 2005 (n = 3), 2006 (n = 6) and 2007 (n = 1)]. 3544 patients (42.6%) were treated before certification and 4779 patients (57.4%) after certification.A highly significant (p 0.001) difference in 100%-GA was found between the various hospitals before certification (min 25.0%; max 54.6%). In 2008, when all participating hospitals were certified, the GA rate was 61.8% (min 39.5%, max 74.4%) and 69.2% (min 45.9%, max 86.4%) for patients75 y (n = 6675). The difference between pre-certification 100%-GA (46.9%) and post-certification (57.2%) was highly significant (p 0.001). RFS and OS were both significantly better after certification compared to the pre-certification period (RFS: HR = 0.79; 95% CI: 0.68-0.92; p = 0.003; OS: HR = 0.75; 95% CI: 0.65-0.85; p 0.001). 5-year RFS (OS) of patients75 y was 89.6% (85.4%) pre-certification and 91.4% (89.5%) post-certification. Since improvement in GA and outcomes correlated as well, GA remains a highly significant prognostic factor for RFS and OS regardless of NPI, intrinsic subtype and adjuvant systemic therapy. This suggests that the certification process is strongly associated with improvements in outcome.

The Z0011 trial has fundamentally changed axillary management in breast cancer patients. However, some important questions remain, like the role of extracapsular nodal extension (ENE) in positive sentinel nodes and the need for further axillary treatment. In this retrospective cohort study, we reviewed and analyzed data from 342 clinically node negative (cN0) breast cancer patients with a positive sentinel node and subsequent axillary lymph node dissection (ALND) from the BRENDA data base. The 104 (30.4%) ENE positive patients had a significantly higher proportion of ≥3 positive axillary lymph nodes (65.0%) compared to ENE negative patients with a positive sentinel node (21.4%). Likewise, ENE positive patients had significantly more often lymph node metastasis size >2 mm (96.2%) than ENE negative patients (72.7%). T1 status was observed significantly more often in ENE negative patients (53.2%) than in ENE positive patients (24.0%). While ENE was linked to worse overall survival in univariate analysis, this effect disappeared when adjusting for nodal status, age, and comorbidities in multivariate analysis. ENE of the sentinel node is an important predictor for nonsentinel lymph node involvement. We suggest that ENE influences survival only via a higher number of positive nodes - one of the most predictive parameters for survival outcome in breast cancer.

Background The decision making process for axillary dissection has changed in recent years for patients with early breast cancer and positive sentinel lymph nodes (LN). The question now arises, what is the optimal surgical treatment for patients with positive axillary LN (pN+). This article tries to answer the following questions: (1) Is there a survival benefit for breast cancer patients with 3 or more positive LN (pN3+) and with more than 10 removed LN? (2) Is there a survival benefit for high risk breast cancer patients (triple negative or Her2 + breast cancer) and with 3 or more positive LN (pN3+) with more than 10 removed LN? (3) In pN + patients is the prognostic value of the lymph node ratio (LNR) of pN+/pN removed impaired if 10 or less LN are removed? Methods A retrospective database analysis of the multi center cohort database BRENDA (breast cancer under evidence based guidelines) with data from 9625 patients from 17 breast centers was carried out. Guideline adherence was defined by the 2008 German National consensus guidelines. Results 2992 out of 9625 patients had histological confirmed positive lymph nodes. The most important factors for survival were intrinsic sub types, tumor size and guideline adherent chemo- and hormonal treatment (and age at diagnosis for overall survival (OAS)). Uni-and multivariable analyses for recurrence free survival (RFS) and OAS showed no significant survival benefit when removing more than 10 lymph nodes even for high-risk patients. The mean and median of LNR were significantly higher in the pN+ patients with ≤10 excised LN compared to patients with > 10 excised LN. LNR was in both, uni-and multivariable, analysis a highly significant prognostic factor for RFS and OAS in both subgroups of pN + patients with less respective more than 10 excised LN. Multivariable COX regression analysis was adjusted by age, tumor size, intrinsic sub types and guideline adherent adjuvant systemic therapy. Conclusion The removal of more than 10 LN did not result in a significant survival benefit even in high risk pN + breast cancer patients.

BackgroundIn this study based on the BRENDA data, we investigated the impact of endocrine ± chemotherapy for luminal A, nodal positive breast cancer on recurrence free (RFS) and overall survival (OS). In addition, we analysed if tumor size of luminal A breast cancer influences survival in patients with the same number of positive lymph nodes.MethodsIn this retrospective multi-centre cohort study data of 1376 nodal-positive patients with primary diagnosis of luminal A breast cancer during 2001-2008 were analysed. The results were stratified by therapy and adjusted by age, tumor size and number of affected lymph nodes.ResultsIn our study population, patients had a good to excellent prognosis (5-year RFS: 91% and tumorspecific 5-year OS 96.5%). There was no significant difference in RFS stratified by patients with only endocrine therapy and with endocrine plus chemo-therapy. Patients with 1-3 affected lymph nodes had no significant differences in OS treated only with endocrine therapy or with endocrine plus chemotherapy, independent of tumor size. Patients with large tumors and more than 3 affected lymph nodes had a significant worse survival as compared to the small tumors. However, despite the worse prognosis of those, adjuvant chemotherapy failed in order to improve RFS.ConclusionsAccording to our data, nodal positive patients with luminal A breast cancer have, if any, a limited benefit of adjuvant chemotherapy. Tumor size and nodal status seem to be of prognostic value in terms of survival, however both tumor size as well as nodal status were not predictive for a benefit of adjuvant chemotherapy.

Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m² doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m² every 28 days or capecitabine 1250 mg/m² twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31). Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.

Background Breast cancer is the most common cancer in women. The German S3 guideline of 2012 has now been updated to take account of advances in the early detection, diagnostic evaluation, treatment, and follow-up care of this disease. Methods The updating process was based on the adaptation of identified source guidelines and on reviews of the scientific evidence. A systematic search in multiple literature databases was carried out, and the full texts of the selected articles were evaluated. Suggested recommendations were then proposed by interdisciplinary working groups and modified and graded in a nominal consensus procedure. Results The value of mammographic screening is confirmed in the updated guideline. As for the diagnostic evaluation of breast cancer, computed tomography is recommended for staging in patients with a high risk of recurrence, in addition to conventional methods. As for surgical treatment, the evidence supporting locoregional surgery for primary breast cancer now affords an opportunity for de-escalation: complete resection yields the best outcome, but a safety margin of several millimeters is not necessary. Axillary dissection is no longer recommended except in certain defined situations. Radiotherapeutic approaches consist of hypofractionated applications. Adjuvant systemic therapy is indicated for patients in certain high-risk situations defined by a constellation of factors including tumor grade, patient age, node status, Ki-67 antigen expression, hormone receptor status, and human epidermal growth factor receptor 2 (HER2) status. All patients with hormone receptor-positive breast cancer should receive endocrine therapy. The indication for chemotherapy and/or anti-HER2 therapy should be determined in consideration of the expected benefit and side effects. Conclusion Consistent implementation of the recommendations in the newly updated guideline can help lessen morbidity and mortality from breast cancer. The actual extent to which breast cancer guidelines are implemented should be a topic of future research.

Geburtshilfe und Frauenheilkunde 78(11), 1056-1088 (2018). doi:10.1055/a-0646-4630, Published by Thieme, New York, NY

Purpose The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y): (1) Is there a significant difference in the distribution of the biological subtypes of oBCP vs younger breast cancer patients (yBCP; 50–69 y)? (2) Which biological subtype has the highest rate of non-guideline-adherent-treatment (GL−) among oBCP? (3) Is a single GL− (i.e. radiotherapy/surgery/endocrine-therapy/chemotherapy) significantly associated with the survival outcome in each biological subgroup? Methods Between 1992 and 2008 the BRENDA (‘BRENDA’ = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714). Results OBCP were more likely to have hormone receptor positive (HR+) and HER2 neu negative (HER2−) breast cancer (77.5% vs 74.5%). The rate of GL− was significantly different (p The survival parameters for HR+/HER2− and TNBC were significantly worse in case of GL− regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR−/HER2+ tumors for GL− for radiotherapy and in HR+/HER2+ tumors for chemotherapy. Conclusions Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP.

Work–life balance is an upcoming issue for physicians. The working group “Family and Career” of the German Society for Gynecology and Obstetrics (DGGG) designed a survey to reflect the present work–life balance of female and male gynecologists in Germany. The 74-item, web-based survey “Profession–Family–Career” was sent to all members of the DGGG (n = 4,564). In total, there were 1,036 replies (23 %) from 75 % female gynecologists (n = 775) aged 38 ± 7 (mean ± standard deviation [SD]) years and 25 % male (n = 261) gynecologists aged 48 ± 11 years. Statistical analyses were performed using the mean and SD for descriptive analysis. Regression models were performed considering an effect of p ≤ 0.05 as statistically significant. 47 % women and 46 % men reported satisfaction with their current work–life balance independent of gender (p gender = 0.15). 70 % women and 75 % men answered that work life and private life were equally important to them (p gender = 0.12). While 39 % women versus 11 % men worked part-time (p gender 0.05). At least 37 % women and men neglected both their partner and their children very often due to their work. Female physicians often described their work situation similar to male physicians, although important differences regarding total work time, overtime work and appreciation by supervisors were reported. Work life affected private life of women and men in a similar way.

The pathogenic impact of tumor-infiltrating B cells is unresolved at present, however, some studies suggest that they may have immune regulatory potential. Here, we report that the microenvironment of various solid tumors includes B cells that express granzyme B (GrB, GZMB), where these B cells can be found adjacent to interleukin (IL)-21–secreting regulatory T cells (Treg) that contribute to immune tolerance of tumor antigens. Because Tregs and plasmacytoid dendritic cells are known to modulate T-effector cells by a GrB-dependent mechanism, we hypothesized that a similar process may operate to modulate regulatory B cells (Breg). IL-21 induced outgrowth of B cells expressing high levels of GrB, which thereby limited T-cell proliferation by a GrB-dependent degradation of the T-cell receptor ζ-chain. Mechanistic investigations into how IL-21 induced GrB expression in B cells to confer Breg function revealed a CD19+CD38+CD1d+IgM+CD147+ expression signature, along with expression of additional key regulatory molecules including IL-10, CD25, and indoleamine-2,3-dioxygenase. Notably, induction of GrB by IL-21 integrated signals mediated by surface immunoglobulin M (B-cell receptor) and Toll-like receptors, each of which were enhanced with expression of the B-cell marker CD5. Our findings show for the first time that IL-21 induces GrB+ human Bregs. They also establish the existence of human B cells with a regulatory phenotype in solid tumor infiltrates, where they may contribute to the suppression of antitumor immune responses. Together, these findings may stimulate novel diagnostic and cell therapeutic approaches to better manage human cancer as well as autoimmune and graft-versus-host pathologies. Cancer Res; 73(8); 2468–79. ©2013 AACR.

Purpose Visceral metastasis of breast cancer (BC) is an alarming development and correlates with poor median overall survival. The purpose of this retrospective study is to examine the risk factors for developing visceral metastasis by considering tumor biology and patient characteristics. Methods Using the BRENDA database, the risk factors such as histological and intrinsic subtypes of BC, age at primary diagnosis, grading, nodal status, tumor size and year of primary diagnosis were examined in univariate and multivariate analysis. Categorical variables were compared by using χ2 tests. Furthermore, multivariate Cox proportional hazards regression models, Kaplan–Meier product-limit method and log-rank test were applied. The results of two tree-building algorithms, “exhausted CHAID” (Chi-squared Automatic Interaction Detector) and CART (Classification and Regression Trees) were verified with further multivariate analysis, radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Results In a patient collective of 886 metastasized patients, 56.9% had developed visceral metastases and 27.1% visceral-only metastases. The different histological and intrinsic subtypes of BC and the grading correlate significantly with the visceral-only metastasis behavior, whereas the age at primary diagnosis, the nodal status, the tumor size and the year of the primary diagnosis had no influence. Patients with ductal/other BC, LuminalB/HER2, TNBC, HER2 overexpressing subtype and grade 3 had an increased risk for the development of visceral-only metastasis. Conclusions Intrinsic and histological subtypes as well as the grading of BC affected significantly the visceral metastasis behavior.

In the treatment of breast cancer, decisions on adjuvant treatment reflect individual patient characteristics like age and comorbidity. This study assessed the association between adherence to guidelines for adjuvant treatment and survival while taking into account age at diagnosis and comorbidities. We collected the Charlson comorbidity index at baseline for 2179 women treated for primary breast cancer from 1992 to 2008 who participated in a German retrospective multicenter cohort study. We assessed subsequent adjuvant therapy guideline adherence and survival in relation to baseline comorbidities. Guidelines for adjuvant chemotherapy and radiotherapy were more often violated in patients with higher Charlson score. Patients with higher Charlson scores received chemotherapy and radiotherapy less often and had higher rates of mastectomy. Irrespective of comorbidity (Charlson score 0, 1-2, ≥3), patients with 100% guideline-adherent adjuvant treatment showed better overall and disease-free survival (DFS) compared to patients with guideline violations (GVs). Controlling for age, comorbidity and tumor characteristics, the hazard ratio for at least one GV was 1.65 (95% confidence interval [CI]: 1.33-2.07) for overall survival and 1.84 (95% CI: 1.53-2.22) for DFS. Guideline-adherent treatment was significantly less frequent in comorbid patients, although guideline adherence was strongly associated with improved survival, irrespective of severity, and number of comorbid diseases.

Background Mammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study. Methods We retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup. Results Overall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p

Background The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. Methods This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms “exhausted CHAID (Chi-square Automatic Interaction Detectors)” and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Results Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p

This retrospective multi-centre study is focussed on recurrence free and overall survival of bilateral breast cancer (BBC) versus unilateral breast cancer (UBC). The impact of BBC on survival is stratified to guideline adherence, according to the German national S3-guideline. Another aim of the study is to identify the influence of various guideline violations in adjuvant treatment on survival of BBC patients. 229 (4.3%) patients had BBC and 5063 (95.7%) had UBC. There is a significant association between BBC/UBC and recurrence free (RFS: p

To evaluate the outcome of frozen-thawed embryo transfer (FET) when freezing takes place at the pronuclear stage, a retrospective analysis was performed comparing spontaneous and artificial cycles.148 women received FET in a spontaneous cycle (Group A) and 55 women received FET in an artificial cycle (Group B) induced by administering estrogen (E2) and progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2, P and luteinizing hormone (LH) were measured. Statistical analysis included the mean, the standard deviation, the Chi-squared test and the T-test.The clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084), with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no difference in endometrial thickness or the P levels, while LH and E2 levels were significantly higher in group B (p 0.0001).Our retrospective study shows a trend towards higher pregnancy rates and live birth rates with the administration of FET during a spontaneous cycle compared to FET during an artificial cycle. Large randomized controlled trials are needed to confirm this trend.

Background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer. We evaluated the efficacy, measured ac cording to the rate of pathological complete response (absence of invasive and intra ductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer. Methods We randomly assigned 1948 patients with a median tumor size of 40 mm on palpa tion to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor–negative dis ease, or hormone-receptor–positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk. Results Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophos phamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevaciz umab, 1.29; 95% confidence interval, 1.02 to 1.65; P = 0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P = 0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor–positive tumors (P = 1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand–foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications. Conclusions The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tu mors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.)

Rationale Understanding and effectively addressing the factors that affect patient compliance with adjuvant aromatase inhibitors (AI) is required in order for patients to obtain maximum benefit from treatment. The CARIATIDE study sought to determine whether the provision of educational materials (EM) could improve compliance and persistence with adjuvant AI. At 1-y follow-up (FU), there was no improvement in overall compliance with AI therapy, compliance with initial AI or persistence rates when EM were provided. Final results from the 2-y FU are presented here. Methods This 2-y, global observational study (NCT00681122) randomized 2758 patients, across 18 countries, to Group A: Standard Therapy or Group B: Standard Therapy + EM. The EM were developed in collaboration with patient advocates, and consisted of a range of information on breast cancer-related topics. Compliance rate with adjuvant AI medication was the primary endpoint. Secondary endpoints included persistence rate after 1 and 2y, and reasons for, and time to, discontinuation of AI therapy. Compliance rate was defined as the proportion of patients being ‘compliant’ with the adjuvant AI medication; switching from AI therapy to tamoxifen would result in a non-compliance score at time of switching. For compliance with initial adjuvant AI medication, switching to another AI or hormone therapy would result in a non-compliance score. A patient was considered a ‘persistent’ user if they did not switch AI medication, AI medication was uninterrupted and there was no discontinuation of the AI medication during the second year. Patients’ compliance and behavior were evaluated using compliance questionnaires, EM feedback and validated questionnaires (EORTC IN-PATSAT32, GHQ-12, FACT-ES). Results Of the 2758 patients randomized at study initiation, 2242 were available for analysis at 2-y FU. The results confirmed those obtained at 1-y FU. No statistically significant difference in compliance with AI therapy was observed between Group A and Group B (82% and 82%, respectively, p=0.9926). Compliance with initial AI was 81% in Group A and 80% in Group B (p=0.5541), with persistence rates of 90% and 88%, respectively (p=0.2425). Of the proportion of patients who had compliance data for both years (Group A n=1118; Group B n=1111) 72% were compliant for the whole 2-y FU period. Across the full 2-y FU, AI treatment discontinuation rates of 8% and 9% were observed in Group A and B, respectively, with discontinuation most frequently attributed to AI-related side effects. Analysis showed that no specific baseline demographic characteristics were associated with compliance behavior. Compliance rates differed widely between countries. Conclusions At 2-y FU, EM were not found to improve overall patient compliance, compliance with initial AI, or persistence with therapy. In total, 72% of patients were compliant across the full 2-y FU. AI-related side effects remained the most frequent cause of AI treatment discontinuation across the full FU period. The 2-y CARIATIDE data confirm the 1-y findings. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-16-02.

Background Long-term use of adjuvant aromatase inhibitors (AI) can be associated with patient non-compliance, but the factors that impact this are currently unclear. A comprehensive understanding of the reasons behind non-compliance is important to inform the design of future interventions intending to improve patient compliance. Educational materials (EM) may improve patients’ treatment compliance, as may demographic characteristics such as country, post-operative chemotherapy, age and BMI. Methods This 2 year, global observational study (NCT00681122) was designed to investigate whether EM could influence patients’ motivation and behavior, and improve treatment compliance with adjuvant AI treatment. Across 18 countries, 2758 patients were randomized 1:1 to Group A: Standard Therapy or Group B: Standard Therapy + EM. EM received by Group B consisted of a range of information on breast cancer related topics. The primary endpoint was compliance rate for the adjuvant AI medication. Secondary endpoints included persistence rate after 1 and 2 years, and reasons for and time to treatment discontinuation of AI. Compliance rate was defined as proportion of subjects being ‘compliant’ with regard to the adjuvant AI medication; switching from AI to tamoxifen would result in a non-compliance score at time of switching. For compliance to initial adjuvant AI medication, switching to another AI or hormone therapy would result in a non-compliance score. A subject was considered a ‘persistent’ user if, during the first year, they did not switch AI medication, AI medication was uninterrupted or there was no discontinuation of the AI medication. Patients’ compliance and behavior were assessed using validated questionnaires (EORTC-INPATSAT-32, GHQ-12, FACT-ES), specifically developed OPTIMA-X, compliance questionnaire and EM feedback in Group B. Results Analysis of 1 year data did not demonstrate statistically significant differences between compliance rates for Groups A and B. Overall compliance was 81% and 82% for Groups A and B, respectively. Compliance with initial AI was reported as 75% for Group A and 77% for Group B, with persistence rates of 84% and 86%, respectively. EM only significantly improved overall compliance in Sweden/Finland (85% and 100%, Groups A and B respectively, p=0.0264, data combined). Demographic sub-group analysis at 1 year gave overall compliance rates of 83% for patients who received post-operative chemotherapy compared with 79% in patients who did not receive post-operative chemotherapy (p=0.0163). Age-group specific compliance for Groups A and B was 70% and 82% at 70y, respectively. Compliance reported in Groups A and B for specific BMI groups was 79% and 81% at BMI 35, respectively. Discussion At 1 year, overall compliance, compliance to initial AI and persistence with therapy was not significantly different between treatment arms. Out of 18 countries, only Sweden/Finland demonstrated a significant improvement in compliance when EM were used. Post-operative chemotherapy was a predictor for patient compliance with AI, but age-group and BMI do not appear to be predictors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-03.

PURPOSE: Cryopreservation, the most important stage of the cryobanking of ovarian tissue, can be carried out using one of two methods: conventional (“slow”) freezing, and vitrification (direct and immediate immersion into liquid nitrogen). For human oocytes and embryos vitrification is more effective compared to conventional freezing. However, these comparative data are limited for human ovarian tissue. The aim of this study was to compare conventional freezing of ovarian tissue with vitrification. MATERIAL AND METHODS: Ovarian tissue from 5 patients was transported to the laboratory within 20 min at 32 to 34 °C, divided into smaller pieces (1 × 1 to 1,5 × 0,7 to 1 mm) and randomly distributed into three groups: Group 1: control (fresh tissue), group 2: pieces after vitrification/warming, Group 3: pieces after conventional freezing/thawing. All pieces were cultured in vitro for 12 days. The viability of the tissue was evaluated by the development of the follicles and GAPDH gene expression after in vitro culture. Results: 93, 74 and 78 % of the follicles of groups 1, 2 or 3 were morphologically normal. Molecular analysis showed that the intensity of GAPDH gene expression in the tissue after conventional freezing was greatly increased compared to after vitrification. CONCLUSION: It was concluded that for the cryopreservation of human ovarian tissue conventional freezing is more suitable than vitrification.

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen. Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom. Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Cryopreservation as a process can be divided into two methods: conventional freezing and vitrification. The high effectiveness of vitrification in comparison with conventional freezing for human oocytes and embryos is shown, whereas data on human ovarian tissue are limited. The aim of this study was to compare the safety and effectiveness of conventional freezing and vitrification of human ovarian tissue. Ovarian tissue fragments from 15 patients were transported to the laboratory within 22–25 h in a special, isolated transport box that can maintain a stable temperature of between 5 and 8 °C for 36 h. Small pieces of ovarian tissue (0.3–1×1–1.5×0.7–1 mm) were randomly distributed into three groups: group 1, fresh pieces immediately after receiving transport box (control); group 2, pieces after vitrification; and group 3, pieces after conventional freezing. After thawing, all the pieces were culturedin vitro. The viability and proliferative capacity of the tissue byin vitroproduction of hormones, development of follicles, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression after culture were evaluated. A difference between freezing and vitrification was not found in respect to hormonal activity and follicle quality. The supernatants showed 17-β estradiol concentrations of 365, 285, and 300 pg/ml respectively, and progesterone concentrations of 3.82, 1.99, and 1.95 ng/ml respectively. It was detected that 95, 80, and 83% follicles respectively were morphologically normal. The molecular biological analysis, however, demonstrated that theGAPDHgene expression in ovarian tissue after vitrification was dramatically decreased in contrast to conventional freezing. For cryopreservation of human ovarian tissue, conventional freezing is more promising than vitrification, because of higher developmental potential.

A German working group of 23 breast cancer experts discussed the results from the vote at this year’s St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer (March 11–14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo)adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed.

Pelvic floor disorders are an increasing problem among elderly women with a high prevalence rate. In the search for new methods to decrease the incidence of recurrent prolapse the use of surgical mesh in pelvic floor surgery has grown in popularity. The use of synthetic materials has resulted in a new spectrum of complications including a mesh erosion rate of up to 19 %. CASE REPORT: A 47-year-old woman was transferred to our clinic under intubation for heavy vaginal bleeding 20 days after vaginal hysterectomy and anterior vaginal wall repair using a transobturator mesh. The mesh was completely visible at the anterior vaginal wall and covered with sanies. The bleeding had ceased by the time of the patient's arrival at our clinic. A blood transfusion was given. The microbiological smear revealed multiresistant Escherichia coli, which was the reason that the antibiotic therapy performed shortly after surgery remained unsuccessful. The visible parts of the mesh were surgically removed. The patient was discharged 2 days later. Six weeks later the vaginal walls appeared well fixed with only a very small erosion which was later removed in an outpatient setting. CONCLUSION: Despite the initial enthusiasm accompanying new surgical techniques we should not forget the special risks involved or the possibility to perform classical pelvic floor surgery. In our opinion, as data is still rare, the use of graft materials in vaginal reconstructive surgery should be limited to a carefully selected patient population. We would like to point out the importance of educating patients about the higher complication rates. Considering the increasing numbers of multiresistant germs, microbiological investigation is essential in cases of postoperative infection.

This study investigates the ability of sucrose to protect spermatozoa against mitochondrial damage, artificial cryoinduction of capacitation, and acrosome reaction. Spermatozoa were isolated using the swim-up procedure performed using three different media: (a) human tubal fluid (HTF, control) medium; (b) HTF with 1% human serum albumin (HSA); and (c) HTF with 1% HSA and 0.25 M sucrose. From each group, 30 μl suspensions of cells were dropped directly into liquid nitrogen and stored for at least 24 h. Cells were thawed by quickly submerging the spheres in HTF with 1% HSA at 37 °C with gentle agitation. Sperm motility, viability, mitochondrial membrane potential integrity, spontaneous capacitation, and acrosome reaction were investigated. Sperm viability, acrosome reaction, and capacitation were detected using the double fluorescence chlortetracycline-Hoechst 33258 staining technique. Mitochondrial function was evaluated using a unique fluorescent cationic dye, 5,5′,6,6′-tetrachloro-1-1′,3,3′-tetraethyl-benzamidazolocarbocyanin iodide, commonly known as JC-1. The number of progressively motile spermatozoa was significantly higher in the sucrose-supplemented medium group (57.1±3.2%,PP

Increasing evidence indicates that breast cancer pathogenesis is linked with DNA double-strand break (DSB) repair dysfunction. This conclusion is based on advances in the study of functions of breast cancer susceptibility genes such as BRCA1 and BRCA2, on the identification of breast cancer-associated changes regarding the genetics, expression, and localization of multiple DSB repair factors, and on observations indicating enhanced radiation-induced chromosomal damage in cells from predisposed individuals and sporadic breast cancer patients. In this pilot study, we describe a sensitive method for the analysis of DSB repair functions in mammary carcinomas. Using this method we firstly document alterations in pathway-specific DSB repair activities in primary cells originating from familial as well as sporadic breast cancer. In particular, we identified increases in the mutagenic nonhomologous end joining and single-strand annealing mechanisms in sporadic breast cancers with wild-type BRCA1 and BRCA2, and, thus, similar phenotypes to tumors with mutant alleles of BRCA1 and BRCA2. This suggests that detection of error-prone DSB repair activities may be useful to extend the limits of genotypic characterization of high-risk susceptibility genes. This method may, therefore, serve as a marker for breast cancer risk assessment and, even more importantly, for the prediction of responsiveness to targeted therapies such as to inhibitors of poly(ADP-ribose)polymerase (PARP1). © 2008 Wiley-Liss, Inc.

The development and implementation of evidence-based, interdisciplinary, consensus-based guidelines is a very important step towards decreasing breast cancer mortality and optimizing the process of early detection, diagnosis, therapy, and follow-up of breast cancer. A revised version of the German S3 guideline was published in February 2008. Different working groups, departments, and organizations participate as coeditors of the new guideline. To fulfill international methodic requirements, a systematic search of the literature with selection of new publications (used as evidence) in the established data bases (Medline, BIOSIS, Previews, CDSR, ACP Journal Club, DARE, CCTR, CINHAL) and the Guidelines International Network (GIN) was performed for the time period of 2003–2006. Varied specialist opinions concerning diagnosis, therapy, and follow-up of breast cancer were considered in formal consensus processes. In different steps, Nominal Group Process techniques, the Delphi technique, and formal consensus processes were used. Besides differently weighted, study-based recommendations, statements resulting from structured consensus finding by the interdisciplinary group – in terms of good clinical practice – were postulated.

We investigated the clinical results and the ultrasonic morphological characteristics of tension-free vaginal tape (TVT) surgery combined with anterior or posterior colporrhaphy in relation to the results after TVT procedure without prolapse repair. Seventy-two women with stress incontinence and other pelvic floor defects underwent the tension-free vaginal tape procedure in conjunction with anterior or posterior colporrhaphy. Another 212 patients with stress incontinence without genital prolapse underwent TVT procedure alone. The study was designed as a prospective investigation. The follow-up was performed 3 months after surgery. The protocol included a standardized questionnaire, gynecological examination, stress test and pad test. The position of the tape was evaluated by introital ultrasound. No differences were found when comparing the groups of patients in terms of complication rates, the rates of improvement or cure of stress incontinence and patient satisfaction. Also, no differences in the characteristics of the tape were identified on ultrasound examination. Additional colporrhaphy does not influence clinical and morphological outcome after TVT and can easily be performed in conjunction with the TVT procedure.

BACKGROUND. Breast-conserving surgery followed by whole-breast radiotherapy (WBRT) has become the standard treatment for the majority of patients with early breast cancer. Whereas the indications for systemic adjuvant treatment have continuously expanded, there is a tendency to restrict postoperative radiotherapy to accelerated partial breast irradiation (APBI) instead of WBRT. METHODS. The different techniques of APBI are described and their respective advantages or potential drawbacks outlined. Moreover, the results described in the literature are briefly reviewed as a basis for the consensus statements and recommendations of the German Society of Radiation Oncology, the German Society of Senology, and the Working Group for Gynecological Oncology of the German Cancer Society. RESULTS. The methods mainly used for APBI are: interstitial radiotherapy with multicatheter technique, intraoperative radiotherapy (IORT) using either electrons produced by linear accelerators or 50 kV x-rays (Intrabeam), the balloon-catheter technique (MammoSite), or 3D conformal external beam radiotherapy. These techniques have marked differences in dose distribution and homogeneity. The published range of local recurrence rates varies between 0% to 37%, the median follow-up from 8 to 72 months. CONCLUSIONS. To date, follow-up times mostly do not yet permit a definite judgment concerning the long-term effectiveness and side effects of APBI. The relevant societies in Germany support randomized clinical studies comparing APBI with WBRT in a well-defined subset of low-risk patients. However, the authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer. Cancer 2007. © 2007 American Cancer Society.

Background: Fear of cancer treatment can become overwhelming. It is important to understand what patients are mainly afraid of and what factors are correlated with intense fear of treatment. Methods: Patients with primary breast cancer (n = 761) completed questionnaires about fear of treatment before surgery (t1), and before (t2) and after (t3) adjuvant treatment. Psychological co-morbidity was assessed using the Patient Health Questionnaire. Logistic regression identified predictors of intense fear of treatment. Results: Patients were most afraid of chemotherapy (mean score 3.5), and fear remained high throughout follow-up; fear of radiotherapy and of surgery was lower and decreased over time (from 2.7 to 2.2, p < 0.0001; and from 2.6 to 2.2, p < 0.0001, respectively). Patients with psychological co-morbidity (odds ratios (OR) 1.7-3.0) and those who had heard reports of negative experiences with cancer treatments from others (OR 3.8-16.2) were more likely to have intense fear of all the treatments. Patients with a previous cancer less often expressed fear of surgery (OR 0.6, 95% confidence interval 0.4-1.0). Conclusion: Fear of treatment, especially of chemotherapy, is prevalent in many patients with primary breast cancer. Patients with psychological co-morbidity and those who have heard reports of negative experiences with cancer treatment are at higher risk of experiencing intense fear. �� In Copyright http://rightsstatements.org/vocab/InC/1.0/ �� In Copyright http://rightsstatements.org/vocab/InC/1.0/, publishedVersion