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Estimating distant recurrence risk in women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer is still challenging. EndoPredict® is a gene expression-based test predicting the likelihood of recurrent disease. We analyzed the difference in oncological decision making with and without the knowledge of gene expression tests. This is a retrospective analysis including patients diagnosed with hormone-receptor positive, Her2 negative breast cancer between 2011 and 2015 at the Municipal Breast Cancer Centre Cologne, Germany. All patients received an evaluation by EndoPredict®. An oncological tumor board (TB) with knowledge of these results served as a baseline (control group). This baseline was compared to the treatment decision (adjuvant chemotherapy yes vs. no) made by oncologists with different experience levels (less than 5 years, between 5 and 15 years, and more than 15 years) who were not provided the EndoPredict® scores. All clinicians had access to clinical as well to histopathological data. There was no significant difference between control group and the oncologists with different experience levels concerning a chemotherapy indication. A trend could be shown in the subgroup of nodal negative patients between the treatment recommendation and physicians with more than 15 years of experience (p = 0.088). A further trend could be demonstrated in the subgroup of patients with a low Ki67 index (≤ 14%) (p = 0.063) between physician with 5–10 years of clinical experience and official treatment recommendation. It seems that inexperienced physicians may profit from the use of EndoPredict® to avoid an overtreatment. In nodal negative patients and patients with a low Ki67 index, undertreatment can be avoided with the use of EndoPredict® (borderline significance). Further prospective studies with larger study cohorts are needed to further validate this tool.

Background: Estimating distant recurrence risk in women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer is still challenging. Oncotype DX and EndoPredict are two competing, gene expression-based tests predicting the likelihood of recurrent disease. We analyzed the difference in oncological decision making with and without the knowledge of gene expression tests. Methods: We performed a retrospective, analysis including n = 192 patients diagnosed with G2, HR+, Her2- breast cancer between 2011 and 2015 at the Municipal Breast Cancer Centre Cologne, Germany. All 192 patients received an evaluation by OncotypeDX or EndoPredict. An oncological tumor board (TB) with knowledge of these results served as baseline (control group). This baseline was compared to the treatment decision (adjuvant chemotherapy Yes vs. No) reached by oncologists with different experience levels (less than 5 years, between 5 and 15 years and more than 15 years) who were not provided the OncotypeDX or EndoPredict scores. All clinicians had access to clinical as well to histopathological data only. Results: Within the EndoPredict group no significant decrease between overall TB decision (adjuvant chemotherapy Yes) 48.1% vs. 15+ years = 39.2%, 5-15 years = 39.2% and 14%, tumor sizes larger than pT2, pN1 and postmenopausal patients for all experience levels. Conclusions: Overall, results for the EndoPredict group were inconclusive. A significant reduction of chemotherapy recommendation was shown for all experience levels in the Oncotype subgroup however, with a maximum reduction of 14.2%. A subgroup analysis showed that differences in decision making were most likely for patients with a Ki67 >14%, tumor sizes larger than pT2, pN1 and postmenopausal patients. Since these are the patients where the question of pro/contra chemotherapy is most important, it is the opinion of this study group that gene expression testing is especially pertinent for these patients. Citation Format: Eichler C, Fromme J, Puppe J, Malter W, Paepke S, Warm M. Gene expression profiling – a decision impact analysis – Decision dependency on OncotypeDX and EndoPredict as a function of oncological work experience [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-21.

Introduction: Tumor biological factors of breast cancer (BC) such as hormone receptor (HR) status, HER2 status, and grade can differ in the metastatic cascade from primary to lymph node (LN) metastasis and to distant metastatic tissue. Systematic data regarding therapeutic consequences are yet limited. Methods: We conducted a prospectively planned, retrospective cohort study comparing BC phenotype in tissue from primary tumors (PTs), locoregional LN metastases, and disease recurrence (DR). HR and HER2 as well as tumor grade in PTs and DR were obtained by a database search. No centralized biomarker testing was performed. The impact of changes in tumor biological factors on post-recurrence survival (PRS) and overall survival was analyzed. Results: PriMet comprises 635 patients (LN tissue in 142 patients). Discrepancies for HR or HER2 status between PT and DR were observed in 18.7 and 21.6% of cases, respectively. For HR status, positivity of PT and negativity of DR was seen more often (13.2%) than vice versa (5.5%). For HER2 status, negativity of the primary and positivity of DR was seen more often (14.9%) than vice versa (6.7%). Discordance was more often observed between PT and LN metastasis compared to LN versus DR. However, numbers were small. Compared to concordant non-triple-negative (TN) disease, concordant TN disease showed significantly inferior PRS. Conclusion: We demonstrate receptor discordance to occur relatively frequently between PT, LN metastasis, and DR and to impact patient prognosis. However, clinical consequences of receptor discordance need to be drawn with caution considering clinical aspects as well as tumor biology.

Background Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Patients and methods Post-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Results Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84). Conclusions These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. Clinical Trials Number CFEM345DDE19.

Background Patients’ compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Background Our recent randomized, multicenter phase III GeparSepto study (Untch M et al. Lancet Oncol 2016) found that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate in patients receiving a sequential regimen of taxane, epirubicin and cyclophosphamide as neoadjuvant treatment for high-risk primary breast cancer. Patients with HER2-positive tumors (32.8%; n=396) also received a combination of pertuzumab and trastuzumab: the present analysis focuses on efficacy and safety data from these HER2+ patients treated with the dual-blockade. Methods Patients with histologically confirmed early breast cancer (n = 1206) received either weekly paclitaxel 80mg/m2 or weekly nab-paclitaxel 150/125mg/m2, according to randomization), followed by four cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab 6 mg/kg (loading (LD) dose 8 mg/kg) and pertuzumab 420 mg (LD 840 mg) q3w for those with HER2-positive tumors. The primary endpoint was pathologic complete response (pCR), defined as ypT0 ypN0. Results The GeparSEPTO trial included 396/1206 (32.8%) HER2+ primary breast cancer patients. 27.0% in the HER2-positive and 34.1% in the HER2-negative group had HR-negative disease. Baseline characteristics were otherwise comparable between HER2+ and HER2- patients. Higher rates of pCR were seen in HER2+, compared to HER2- tumors (57.8% vs 22.0%). The highest overall pCR rate was observed in the HER2+/HR- cohort with 71.0%; 66.7% with Pac and 74.6% with nab-Pac. In HER2+/HR+ pCR rate was 52.9% ; 49.4% with Pac and 56.4% with nab-Pac. Using the definition ypT0/is ypN0 for pCR; pCR rates were generally higher especially in the HER2+ cohort (66.2% (ypT0/is ypN0) vs 57.8% (ypT0 ypN0)) compared to 25.2% (ypT0/is ypN0) vs 22% (ypT0 ypN0)) in patients with HER2-negative tumors. The HER2+ patients experienced a significantly higher incidence of grade 3-4 adverse events 85.4% vs 78.0% in the HER2-cohort, p=0.003); grade 3-4 hematologic AEs 74.0% (HER2+) vs 69.5% (HER2-); p=0.120 with grade 3-4 anaemia 2.5% vs 0.9%; p=0.034); any grade thrombopenia 28.5% vs 21.8%; p=0.012) and febrile neutropenia 6.3 vs 3.3%; p=0.023. Any grade 3-4 non-haematological toxicities occurred in 38.4% vs 30.1%; p=0.005), with grade 3-4 diarrhea occurring in 7.6% vs 0.9%; p Conclusion This is the largest cohort of patients with HER2-positive early breast cancer receiving a dual HER2-targeted neoadjuvant therapy of pertuzumab and trastuzumab, together with nab-paclitaxel or paclitaxel followed by epirubicin and cyclophosphamide. HER2+ patients experienced more noteworthy toxicity. The pCR rate were higher in the HER2+ cohort receiving the dual blockade and was highest in patients with in HER+/HR- particularly if nab-paclitaxel was substituted for paclitaxel. The trial is financially supported by Celgene and Roche. Citation Format: Loibl S, Jackisch J, Schneeweiss A, Schmatloch S, Aktas B, Denkert C, Schem C, Wiebringhaus H, Kuemmel S, Luebbe K, Warm M, Just M, Hanusch C, Hackmann J, Blohmer J-U, Clemens M, Engels K, Nekljudova V, von Minckwitz G, Untch M. Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: A subanalysis of data from the randomized phase III GeparSepto trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-06.

Introduction The GeparSepto study showed that the substitution of paclitaxel (P) with nab-paclitaxel (nP) followed by epirubicin/cyclophosphamide (EC) as neoadjuvant chemotherapy increased the rate of pathological complete response (pCR) from 29% to 38% (p Patients and Methods In the GeparSepto trial (NCT01583426) patients were randomized in a 1:1 ratio to receive either nP 125mg/m2 or P 80 mg/m2 q1w for 12 weeks followed by 4 cycles of conventionally dosed EC (E: 90mg/m2; C: 600 mg/m2) q3w (Furlanetto et al. Annals Oncol 2016). Patients with HER2+ tumors received trastuzumab 6(8)mg/kg q3w and pertuzumab 420(840)mg q3w concomitantly to all chemotherapy cycles (Loibl et al. Annals Oncol 2016). Patients with untreated, histologically confirmed uni- or bilateral, cT2- cT4d breast carcinoma, and no clinically relevant cardiovascular and other co-morbidities were included. Primary objective was pCR rate (ypT0 ypN0). Secondary objectives were invasive disease-free survival (IDFS), and overall survival (OS) overall and according to stratified subpopulations, amongst other time to event endpoints, quality of life focusing on peripheral sensory neuropathy (PNP), treatment of PNP, and cardiac toxicity, detection of circulating tumor (ct) DNA at the time of surgery and during follow up and correlation with pCR and early relapses. The IDFS analysis is planned after 248 events have occurred. The log-rank test will have 80% power to detect an improvement of the 5 year IDFS from 75% to 81.8% (HR=0.70) at a 2-sided significance level of α=0.05. Results In 69 German centers, 1229 patients were randomly assigned (07/2012 – 12/2013) to receive either nP (606) or P (600). nP was given for the majority of cycles at a dose of 150mg/m2 to 179 patients and at a dose of 125mg/m2 to 426 patients. Follow-up is still ongoing. The expected number of events will be awaited for October 2017. Conclusion Neoadjuvant GeparSepto study demonstrated a significantly higher pCR rate when patients received nP instead of P as part of an anthracycline/taxane based sequential chemotherapy. The expected long-term results will help to assess the overall benefit of nP in BC and the surrogate value of pCR for survival endpoints. Citation Format: Schneeweiss A, Jackisch C, Schmatloch S, Aktas B, Denkert C, Schem C, Wiebringhaus H, Kümmel S, Rhiem K, Warm M, Fasching PA, Just M, Hanusch C, Hackmann J, Blohmer JU, Gerber B, Furlanetto J, von Minckwitz G, Nekljudova V, Loibl S, Untch M. Survival analysis of the prospectively randomized phase III GeparSepto trial comparing neoadjuvant chemotherapy with weekly nab-paclitaxel with solvent-based paclitaxel followed by anthracycline/cyclophosphamide for patients with early breast cancer – GBG69 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-05.

Background: We previously reported that nab-paclitaxel (nP) increases the pathological complete response (pCR, ypT0 ypN0) rate when it replaces solvent-based paclitaxel (P) as part of a sequential taxane followed by epirubicin/cyclophosphamide (EC) neoadjuvant chemotherapy for patients with early breast cancer (Untch et al. SABCS 2014). Here, we report efficacy and safety of patients being treated either with 150 mg/m2 nab-paclitaxel (nP150) before an amendment or with 125 mg/m2 nab-paclitaxel (nP125) thereafter in comparison to solvent-formulated paclitaxel at 80 mg/m2 (P80). Methods: In the GeparSepto study (NCT01583426), 1207 patients were randomized to either nP150 or P80 q1w for 12 weeks followed by 4 cycles of conventionally dosed EC (E: 90mg/m2; C: 600 mg/m2) q3w. The primary objective of the study was to compare the pCR rate (pCR, ypT0 ypN0). Patients with untreated, histologically confirmed uni- or bilateral, cT2- cT4d carcinoma, and no clinically relevant cardiovascular and other co-morbidities were included. Patients with HER2+ tumors received trastuzumab (loading dose 8mg/kg; 6 mg/kg) plus pertuzumab (loading dose 840 mg; 420 mg) q3w concomitantly to all chemotherapy cycles. After a safety analysis showed a higher rate of dose reductions and treatment discontinuations with nP150 compared to P80, weekly dose of nP was reduced to 125 mg/m2. Results: nP was given for the majority of cycles at a dose of 150 mg/m2 to 179 patients and at a dose of 125 mg/m2 to 426 patients. Treatment characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for HER2 status (HER2-positive: nP150 22%, nP125 37% and P80 33%) and Ki67 ( Conclusions: Risk-benefit ratio of nP125 was improved over nP150 with better drug adherence and RTDI, lower frequency of PNP but a higher pCR rate. It should therefore be considered as the preferred schedule when nP is used as neoadjuvant treatment for primary breast cancer. The trial was financially supported by Celgene and Roche. Citation Format: von Minckwitz G, Untch M, Jakisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Weibringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer J-U, Clemens M, Costa SD, Gerber B, Nekljudova V, Loibl S. nab-paclitaxel at a dose of 125 mg/m2 weekly is more efficacious but less toxic than at 150 mg/m2. Results from the neoadjuvant randomized GeparSepto study (GBG 69). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-11.

Introduction: The use of acellular dermal matrices (ADM) has become a widely used option in breast reconstruction. A great deal of literature is available, totaling over 2400 ADM reconstructions. Nonetheless, head to head comparisons between SurgiMend® and Epiflex® are not yet reported. In fact, this is the first clinical data report on the use of Epiflex®. This work will therefore compare postoperative complication rates and costs for these ADMs. Methods: This analysis is a retrospective review of a single surgeon's 6-year experience with both SurgiMend® – an acellular bovine dermal collagen matrix for soft-tissue reconstruction and Epiflex® – a decellularized human skin tissue from 2008 to 2013. Results: One hundred patients had a total of 127 implant based reconstructions using SurgiMend® (64 cases; 50.4 %) or Epiflex® (63 cases; 49.6%). Gross complication rates were 11.1 % for SurgiMend® and 40.6 % for Epiflex® including hematoma, postoperative skin irritation, infection, necrosis and revision surgery. The most common complication was postoperative red breast syndrome . Severe complications requiring revision surgery were significantly increased in patients treated with Epiflex® (12.5 %) compared to SurgiMend® (4.8 %). Conclusions: This retrospective analysis favors the use of SurgiMend® over Epiflex® due to significantly lower gross complication rates. Severe complication rates are comparable to those reported in literature for both products. Although results promote the use of SurgiMend®, the single surgeon, retrospective nature of this work limits its clinical impact. Citation Format: Eichler C, Vogt N, Brunnert K, Sauerwald A, Puppe J, Warm M. A head to head comparison between SurgiMend® - Fetal bovine acellular dermal matrix and Epiflex® - Decellularized human skin tissue in breast reconstruction in 127 cases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-13-05.

Background We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC). Patients and methods A total of 379 eligible women with estrogen receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded. Results Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice. Conclusion RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.

Background: Breast cancer patients make frequent use of complementary and alternative medicine (CAM), but few prospectively collected data are available specifically for postmenopausal breast cancer patients receiving adjuvant antihormonal therapy. The aim of the study was to identify the characteristics of patients who are interested in integrative medicine (IM). Methods: The EvAluate-TM study is a prospective noninterventional study, in which treatment with letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. 5,045 patients were enrolled at 339 certified breast centers. As part of the data collection process, patients were asked at the baseline about their interest in and information needs about IM. Results: 3,411 patients responded to the questionnaire on IM and took part in the analysis. 1,583 patients expressed an interest in IM. Relevant predictors of interest in IM were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in IM declined highly significantly (P < 0.001) with age. In addition, these women were mostly interested in receiving information about their disease from a physician. Conclusions: This study shows that postmenopausal women have a strong interest in IM. Information about IM should therefore be included in patient care for this patient group. Especially the patients receiving concomitant medication, which is one of the main predictors for women not being interested in IM, may need special attention. In addition, most patients were interested in obtaining the relevant information from their doctor, indicating that responsibility for this lies with the treating physicians.

The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany.A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually.The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care.Country-specific data on the risk of distant recurrence and quality-of-life were not available.Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.

Introduction Post-mastectomy seroma, with an occurrence of up to 59%, is a major complication in modern oncological surgery. While drain placement is a common tool in dealing with this complication, some patients may either be incapable or unwilling to accept this course of action, requiring an alternative option for seroma prevention. A recent study using a lysine-derived urethane adhesive named TissuGlu® has shown promising results in mastectomy patients. Case presentation We used TissuGlu® in three patients who could not have a post-operative drain after mastectomy due to a variety of reasons. Standard mastectomy protocols were followed. Two no-drain mastectomy patients did not show any post-operative seroma formation (cases 1 and 2), while a third patient had to be aspirated twice at two (180 ml) and four weeks (60 ml) post-surgery. No complications such as hematoma, wound dehiscence or adverse reactions to the adhesive were observed. Patient satisfaction with the no-drain situation was high as post-surgical discomfort was minimal. Conclusion Although one patient developed small amounts of seroma, TissuGlu® may present an additional option in the high risk, no-drain post-mastectomy scenario.

Background: PELICAN is a phase III trial of pegylated liposomal doxorubicin (PLD) vs capecitabine (CAP) as first-line therapy of patients (pts) with MBC. In the elderly pts, a CGA and analyses on biologic parameters on inflammation and nutrition, incorporated in the Prognostic Inflammatory and Nutritional Index (PINI) and Glasgow Prognostic Scale (GPS), were performed and results correlated to time to progression (TTP), overall survival (OS), time to treatment failure (TTF), and toxicity. Methods: CGA comprised data on activities of daily living (ADL), instrumental activities of daily living (IADL), ECOG and Karnofsky performance score (KPS), comorbidity (CIRS-G), and comedication. According to CGA, pts were classified into groups 1-3, ranging from fit to frail (Balducci 2000). For biologic assessment, blood samples of 86 pts were collected and centrally analysed. PINI was defined as [(CRP (mg/L) x A1GP (mg/L)]/[albumin (g/L) x prealbumin (mg/L)]. For GPS: pts were allocated a score of 2 if CRP >10mg/L and albumin Results: 210 pts (PLD:105; CAP:105) were randomized, stratified by age & prior anthracycline. Median age was 62y (22-85). Pts received a median of 5 cycles each of PLD and CAP. Median TTP was comparable in both arms (6.7mo PLD vs 7.1mo CAP, p=0.346). There was an insignificant trend for higher GPS and PINI in pts ≥65y. According to CGA, 102 pts were considered fit (group 1, 72%), 21 compromised (group 2, 15%), and 19 frail (group 3, 13%). CGA did not correlate with therapy efficacy. Pts with good KPS of ≥90% (n=46) had a significantly longer TTP vs pts with a worse KPS (n=44) (median KPS 100%: 8.7mo; 90%: 8.6mo; ≥90%: 3.8mo; p=0.0027). Pts with GPS of 0 or 1 had a significantly longer TTP and TTF vs pts with a GPS of 2 (median TTP score 0: 8.3mo, score 1: 9.2mo, score 2: 2.8mo, p=0.0002). Grouping of pts by PINI values (10) showed no correlation with TTP or TTF, and a nonsignificant trend for shorter OS for pts with PINI >10 (p=0.056). Among the analyzed laboratory parameters as single values, CRP showed a significant correlation with TTP (median TTP ≥5mg/L: 10.4mo, > 5 mg/l: 6.2mo, p=0.031) as did serum amyloid A (SAA, median TTP ≥6.8mg/L: 10.4mo, >6.8mg/L: 6.0mo, p=0.026) and serum albumin (median TTP ≥35g/L: 8.3mo, Conclusions: First-line chemotherapy of MBC pts using PLD or CAP showed similar efficacy with respect to TTP. Incorporation of CGA into a phase III trial is feasible and yields information that would otherwise have been missed. Prospective analyses of parameters of systemic inflammation and nutrition may have prognostic significance regarding TTP, TTF, and potentially OS in pts with breast cancer. Results of CGA, PINI and GPS need to be validated prospectively in treatment algorithms for this population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-06.

Background: Both the Oncotype DX multi-gene assay and invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy in primary breast cancer (BC). Material and Methods: The West German Study Group (WSG) Plan B trial (planned n=2,448) is evaluating anthracyline-free adjuvant chemotherapy (6x TC) vs. standard 4xEC-4xDOC in HER2- negative BC with 0-3 positive lymph nodes, Oncotype DX is used as selection criterion where pts with RS> 11 are randomized to one of the two chemotherapy arms and pts with RS ≥11 treated with hormonal therapy alone. uPA/PAI-1 (both low vs. either/both high), measured by ELISA, is obtained as an optional risk factor. Results: By June 2010, 1064 patients had been randomized in Plan B (96 recruiting centers). In 153 patients (27 centers), uPA and PAI-1 had been measured; for 131 (84 N0, 47 N+) of these, Oncotype DX Recurrence Score® (RS) results were also available. When considered as continuous variables, RS was weakly positively correlated (Spearman's coefficient) with uPA (rs=0.18, p=0.04) and with PAI-1 (rs=0.23, p=0.01). When considered as risk categories/(Table 1), there was a weak concordance between RS and uPA/PAI-1, using either the standard RS cutoff points (18 and 30) or the TAILORx trial cutoff points (11 and 25). Table T: Association between RS and uPA/PAI-1 categories Assignment of high risk was most strongly concordant between uPA/PAI-1 and RS (RS > 25: 22/25 patients had high uPA/PAI-1; RS >30: 14/15 patients had high uPA/PAI-1). This high-risk concordance extends to N0 patients (RS>25: 17/19 N0 pts had high uPA/PAI-1; RS>30: 11/12 pts had high uPA/PAI-1). Discussion: For the first time, risk groups in primary breast cancer according to both Oncotype DX and uPA/PAI-1 have been compared. These preliminary data show that the high RS group seems highly concordant with the prospectively assessed invasion markers uPA/PAI-1. However, within low and intermediate RS, uPA/PAI-1 could still identify a substantial collective at risk; low uPA/PAI-1 could define a clinically relevant low-risk collective within risk groups that would be classified as “intermediate” according to the multigene assay Oncotype DX. Additional recruitment and outcome assessment of the ongoing multicenter WSG Plan B trial will address the clinical significance of these findings. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-05.

Previous studies have already shown a survival benefit in sub groups of metastatic breast cancer treated with bisphosphonates. Zoledronate given monthly to patients with metastatic disease to the bones showed a reduction in mortality of 32% [1]. Conceivable mechanisms include changes in the microenvironment of tumor cells, induction of apoptotic pathways, reduction of angiogenesis and cell adhesion [2-7]. Moreover, zoledronate interferes with the interaction between tumor cells and the bone marrow microenvironment. Bone metabolism is reduced, and proliferation requirements are disrupted in a major target location of metastatic disease. All these effects seem to be independent of the estrogen receptor status or grading of the primary breast tumor. There is accumulating evidence that adjuvant treatment with zoledronate improves progression and recurrent free survival in estrogen receptor positive breast cancer independent of the menopausal status. Although the use of zoledronic acid in the adjuvant setting is still off label, it has become a major corner stone in everyday clinical practice. Moreover, also in the special situation of triple negative or estrogen receptor negative breast cancer with a high risk of recurrence, zoledronate is increasingly used both within clinical trials and in individual cases.

12102Background: In triple-negative breast cancer (TNBC), pathological complete response (pCR, ypT0/is/ypN0) is associated with improved prognosis. The randomized prospective WSG-ADAPT TN phase II ...

Bei Patientinnen im Senium wird dem Aspekt der Brusterhaltung zunehmend grosere Bedeutung zugemessen. Aktuelle Daten bestatigen das Konzept der neoadjuvanten endokrinen Therapie als Option bei postmenopausalen Frauen zur Volumenreduktion lokal fortgeschrittener Karzinome und damit der Erhohung der Rate brusterhaltender Operationen. Des Weiteren ist die In-vivo-Testung der Effektivitat unter neoadjuvanter endokriner Therapie fur die anschliesende adjuvante Therapie von Bedeutung. Auserdem zeichnet sich die endokrine Therapie durch eine gute Vertraglichkeit aus. Sowohl fur Tamoxifen als auch fur alle Aromatasehemmstoffe liegen, wenn auch in unterschiedlichem Umfang, aktuelle Daten vor. Erste neoadjuvante Therapiestudien mit Tamoxifen zeigten klinische Ansprechraten von 49 bis 68 % mit einer Reduktion des Tumorvolumens von median 58 %. Studien, die eine adjuvante mit einer primaren Tamoxifengabe mit nachfolgender Operation im Falle der Krankheitsprogression verglichen, fanden keinen Unterschied im Gesamtuberleben. Fur die Aromatasehemmstoffe liegen Ergebnisse verschiedener Studien vor: In der IMPACT-Studie (Phase III) weisen Anastrozol, Tamoxifen und die Kombination beider nach 3 Monaten keine Unterschiede im Ansprechen auf (Anastrozol 37,2 %, Tamoxifen 36,1 %). Durch Anastrozol wird eine erhohte Rate brusterhaltender Operationen (45,2 %) im Vergleich zu Tamoxifen (22,2 %) erreicht. Exemestan fuhrt mit 88,6 % zu einem hoheren Ansprechen als Tamoxifen (57,2 %) (Phase II) und Letrozol von 55 - 92 % vs. 36 % gegenuber Tamoxifen (Phase II und III). Eine Verlangerung der neoadjuvanten Therapiephase mit Exemestan auf 4 - 5 Monate verbessert das Ansprechen mit zusatzlich erhohter Rate an klinisch und pathologisch nachgewiesenen Komplettremissionen und einer erhohten Rate der Brusterhaltung von 45,2 %; mit Letrozol 6 - 8 Monate auf 67,0 %. Daten zum Langzeitverlauf stehen aus. Zukunftige Studien fokussieren auf die Optimierung der Therapiedauer, die Suche nach zuverlassigen pradiktiven Markern und die Verbesserung des therapeutischen Index. For elderly women, great importance is increasingly being attached to the question of breast conservation. Current data confirms the concept of neoadjuvant endocrine therapy as an option in postmenopausal women to reduce the volume of locally advanced carcinomas and thereby increase the rate of breast conserving operations. Moreover, in vivo testing of the effectiveness of endocrine neoadjuvance is important for subsequent adjuvant therapy. Endocrine therapy is also particularly well tolerated. Current data are available, although to different degrees, both for tamoxifen and for all aromatase inhibitors. Initial neoadjuvant treatment studies with tamoxifen showed clinical response rates of 49 to 68 % with a median reduction in tumour volume of 58 %. Studies comparing adjuvant tamoxifen with primary tamoxifen treatment and subsequent surgery in the event of disease progression found no difference in total survival. For the aromatase inhibitors, results were variable overall: In the IMPACT study (Phase III) anastrozole, tamoxifen or the two drugs combined showed no difference with respect to response after 3 months (anastrozole 37.2 %, tamoxifen 36.1 %); an increased rate of breast conserving operations was achieved with anastrozole (45.2 %) compared with tamoxifen (22.2 %). Exemestane, at 88.6 %, has a greater response than tamoxifen (57.2 %) (Phase II) and letrozole shows a response of 55 - 92 % compared with 36 % for tamoxifen (Phase II and III). Extension of the neoadjuvant therapy phase with exemestane to 4 - 5 months improved the response, with further increases in the rates of complete remission based on clinical and pathological evidence and an increased rate of breast conservation of 45.2 %; figures for letrozole at 6 - 8 months were 67.0 %. Data on the long-term outcome are not yet available. Future studies are focusing on optimisation of the treatment period, the search for reliable predictive markers and improvement of the therapeutic index.

PURPOSE: To evaluate preoperative contrast enhanced MR imaging in clinically, mammographically and/or ultrasonographically established breast cancer. MATERIALS AND METHOD: From September 1998 to August 1999, preoperative contrast-enhanced MR imaging of the breast was performed in 91 patients with lesions highly suggestive of malignancy (BIRADS IV and V) by clinical, mammographic, and/or ultrasonographic criteria. MR imaging findings were postsurgically correlated with other imaging, intraoperative and histopathologic results. RESULTS: Histopathologic analysis revealed 61 (66 %) malignant and 31 (34 %) benign lesions. In 63 (69 %) of the 91 investigated patients, MR mammographies were classified as tumor suspect and in the remaining 28 (31 %) cases as benign. The sensitivity, specificity and accuracy were 90 %, 67 % and 81 % for contrast-enhanced MR imaging. Additional tumor manifestations (multifocal or multicentric disease, contralateral carcinoma) were found by MR imaging alone in 10 patients (11 %). CONCLUSION: Contrast-enhanced MR imaging may reveal unsuspected multifocal, multicentric or contralateral breast carcinoma that changes the surgical therapy if the intention is total tumor removal. The prognostic role of a potentially more radical surgical therapy on the basis of these findings is not clear.

Background: Pathological complete response (pCR) is associated with improved prognosis in TNBC, but optimal chemotherapy remains unclear. Use of weekly nab- paclitaxel (Nab-Pac) vs. conventional paclitaxel and also addition of carboplatinum(Carbo) to anthracycline-taxane(A/T) containing chemotherapy results in significantly higher pCR rates in TNBC with unclear impact on survival and increased toxicity. The ADAPT study seeks to compare Carbo vs. gemcitabine(Gem) added to nab- paclitaxel as a short 12-week A-free regimen. It also assesses efficacy in early responders vs. non-responders by 3-week proliferation and/or imaging response. Methods: ADAPT TN compares 12-week neoadjuvant regimens: Carbo vs. Gem combined with Nab-Pac and aims to identify early-response markers for pCR (yPN0 and ypT0/is). TNBC patients (centrally confirmed ER/PR Results: 336 patients were enrolled from 47 centers between 06/13-02/15 (n=182 ArmA: Nab-Pac/Gem and n=154 ArmB: Nab-Pac/Carbo). 90% and 95% completed therapy according to protocol respectively (n.s.). Median age was 50y. At baseline: A/B: 73% and 74%% had G3 tumors, median Ki-67 of 70% and 75%; 62.6% and 62.9%% had cT2-4c tumors, pN0 status prior to chemotherapy was confirmed in 50.5% and 50%, respectively. pCR (ypT0/is/ypN0) was A: 28.7% and B: 45.9% (p Nab/Gem arm was associated with significantly higher frequency of dose reductions (20.6% vs. 11.9% (p=0.03), treatment related SAE's (13% vs. 5%, p=0.02), grade 3-4 infections (6.1% vs. 1.3%, p=0.04) and ALAT elevations (11.7 vs. 3.3%, p=0.01) compared to the Nab-Carbo arm. Within the planned interim analysis (n=130: A/B: 69/61), baseline Ki-67 (Nab- Pac/Carbo arm), age>50 years, and low cellularity ( Validation of responder definitions for the whole study will be presented at the meeting. Conclusions: This is the first large randomized study comparing two short 12-week anthracycline- free regimens in unselected TNBC. Our results suggest superior efficacy and excellent toxicity of Nab-Pac/Carbo vs. Gem. Longer A/T-Carbo containing regimens render quite comparable pCR rates, thus overtreatment by 4xEC in unselected TNBC may be present in some patients. Early response criteria seem to differ according to regimen; their assessment may be impaired by substantial tumor necrosis already after the first therapy cycle. Citation Format: Gluz O, Nitz U, Liedtke C, Christgen M, Sotlar K, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, Aktas B, Schumacher C, Bangemann N, Lindner C, Kuemmel S, Clemens M, Potenberg J, Staib P, Kohls A, Pelz E, Kates RE, Wuerstlein R, Kreipe HH, Harbeck N. Comparison of 12 weeks neoadjuvant Nab-paclitaxel combined with carboplatinum vs. gemcitabine in triple- negative breast cancer: WSG-ADAPT TN randomized phase II trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr S6-07.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1–5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5–10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Background: WSG-ARA plus trial evaluated the effect of adjuvant darbepoetin alfa (DA) on outcome in node positive primary breast cancer (BC). Patients and methods: One thousand two hundred thirty-four patients were randomized to chemotherapy either with DA (DA+; n = 615) or without DA (DA-; n = 619). DA (500\textgreekmg q3w) was started at hemoglobin (Hb) levels \15g/dl were reported in 0.8\% of cycles. QoL parameters did not significantly differ between arms. At 39 months, DA had no significant impact on EFS (DA+: 89.3\%, DA-: 87.5\%; Plog-rank = 0.55) or OS (DA+: 95.5\%, DA-: 95.4\%; Plog-rank = 0.77). Conclusions: DA treatment did not impact EFS or OS in routine adjuvant BC treatment. \copyright The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Introduction Post-mastectomy seromas are a common problem in modern oncological surgery. Occurrence rates of up to 59% have been reported in the literature. High-risk patients, that is, those who have received previous surgeries, radiation or chemotherapy, present a particular challenge. Several surgical techniques, including progressive tension suture application, have shown promise. Noninvasive measures such as fibrin-based adhesives have thus far not been able to prevent seroma occurrence effectively. A recent study using a lysine-derived urethane adhesive named TissuGlu®, however, showed promising results in patients after abdominoplasty. Case presentation We used TissuGlu® to treat a high-risk 64-year-old female patient with a history of breast cancer and severe post-mastectomy seroma. The postsurgical period showed successful seroma suppression, without any adverse effects or complications. Conclusions This type of adhesive should be evaluated as an alternative, less-invasive option for preventing seroma in patients after a mastectomy.

597Background: Patients (pts) with HER2-negative (HER2-) advanced metastatic breast cancer (MBC) may present with elevated serum levels of the HER2 extracellular domain (sHER2) or HER2 overexpressing circulating tumor cells (CTCs), potentially qualifying for anti-HER2 therapy. This retrospective study sought to clarify the value of HER2-directed Tx in ´occult´ HER2-positive (HER2+) MBC pts in the clinical routine. Methods: 31 pts with HER2- MBC (ER+, n = 27) exhibiting sHER2 values > 15 ng/mL (n = 8), HER2+ CTCs (n = 7), or both (n = 16) were included. Pts had failed 2-16 prior systemic treatments (median: 7). Pts received trastuzumab (T: n = 19), lapatinib (L: n = 4), T+L (n = 2), or T+pertuzumab (TP: n = 6). Anti-HER2 Tx was given alone (n = 5), or in combination with endocrine agents (n = 6), cytotoxics (n = 17), or other targeted drugs (n = 3). Responses were scored according to RECIST 1.1, OS was calculated from the start of Tx until death from any reason or loss to follow-up. Results: Anti-HER2 Tx w...

A randomized phase III trial was conducted in patients with advanced ovarian cancer FIGO IIB–IV in order to determine whether epirubicin (E) in addition to paclitaxel (T) and carboplatin (C) will increase survival in comparison to TC alone. The rationale of this study was based not only on the evidence of activity of free and liposomal anthracylins in patients who have been pretreated with the platinum–paclitaxel regimen but also on the evidence of meta-analyses performed before the taxane era of a 7% improvement in survival when doxorubicin was added as the third agent in first-line treatment (Ovarian Cancer Meta-analysis Project. J Clin Oncol 1991;9:1668–74). In addition, there were some reports suggesting a synergistic activity between paclitaxel and anthracylins (Ray-Coquard I et al. Gynecol Oncol 2003;88:351–7) in patients with ovarian cancer in relapse. Between November 1997 and February 2000, 1282 patients were randomized to receive six cycles of either T 175 mg/m2 3 h iv + C area under curve 5 (according to the Calvert formula) + E 60 mg/m2 iv (TEC) or TC at same doses, both in 3-week intervals. Patients were stratified per centre and into one of two strata according to FIGO stage and residual tumor size: stratum I includes patients with FIGO IIB–IIIC and residual tumor ≤1 cm and stratum II patients with FIGO IIB–IIIC and residual tumor >1 cm or FIGO IV. The primary end point was overall survival (OS). Secondary end points included toxicity, response to treatment, quality of life, and progression-free survival (PFS). Median follow-up at the time of analysis was 51.9 months. The whole population is available for PFS and OS analysis. A total of 1264 patients received at least one cycle of treatment and are evaluable for toxicity. Patient characteristics are well balanced between the two arms with respect to median age, performance status, FIGO stage, histology, and stratification, with less than one third of the patients suboptimally debulked. The three-drug combination induced a markedly higher myelotoxicity resulting in increased demand on supportive care. Grade 3/4 febrile neutropenia occurred in 5.5% patients in TEC and in 1.3% patients in TC (P

Background: Clinical evidence for the anticancer activity of adjuvant zoledronic acid (ZOL) in patients with early stage breast cancer (BC) has been reported in several randomized clinical trials including ZO-FAST, AZURE (>5 yr postmenopausal subset), and ABCSG-12. In addition, combining ZOL with standard neoadjuvant therapy improved pathologic complete response (pCR) and reduced the need for mastectomy in the AZURE trial. The open-label, multicenter, phase 2, FEMZONE trial examined the effect of neoadjuvant letrozole (LET) ± ZOL on tumor response in postmenopausal patients with hormone receptor-positive (HR+) primary BC. Here, we report the efficacy and safety after 6 mo of treatment. Methods: Postmenopausal women with HR+ BC and ECOG performance status of 0–2 were randomized to LET (2.5 mg/d) ± ZOL (4 mg q4w). The primary efficacy endpoint was objective response rate (ORR; complete + partial response per RECIST criteria) at 6 mo by central review. Secondary endpoints included ORR in the per-protocol and safety populations, best response, breast-conserving surgery, pCR, change in tumor size, overall survival, and safety. Between-group differences in ORR were evaluated using Fisher's exact test. Results: Among enrolled patients (N = 168; mean age 70.9 yr; mean treatment duration 6.5 mo), patients receiving LET + ZOL experienced numerically better ORR at 6 mo versus LET alone (69.2% vs 54.5%, respectively), with a between-group difference of 14.7% (P = .106). Although the primary endpoint did not reach statistical significance because of insufficient patient recruitment, the prespecified between-group difference of ≥10% was met. A similar trend in ORR at 6 mo favoring ZOL was also seen by local assessment (Δ11%, P = .192). At 4 mo, higher ORR was observed for LET + ZOL versus LET alone both for the local (33.3% vs 24%, respectively) and central assessments (41.5% vs 30.3%, respectively). Numerically more patients receiving LET + ZOL experienced a partial response at 6 mo versus LET alone (66.2% vs 54.5%, respectively). At 6 mo, the mean tumor size had decreased from 3.34 ± 1.98 cm to 2.1 ± 1.76 cm in the overall patient population, and the decrease was slightly larger with LET + ZOL compared with LET alone (–1.37 ± 0.96 cm vs −1.12 ± 0.92 cm, respectively). Overall, there was no difference in the number of patients requiring mastectomy between LET + ZOL and LET alone (15.6% vs 15.2%, respectively). Incidence of adverse events (AEs) was slightly higher among patients receiving LET + ZOL versus LET alone (92.1% vs 81%, respectively), and the types of AEs were consistent with the known safety profiles of these agents. No deaths or osteonecrosis of the jaw was reported during the course of the study. Conclusions: This study provides additional confirmation of the efficacy of LET as neoadjuvant therapy for early HR+ BC, and supports previous reports of ZOL's anticancer activity in this setting (as evidenced by the trend toward improved ORR with ZOL + LET versus LET alone). These data, together with other published ZOL studies, suggest that adding ZOL to neoadjuvant therapy may be considered for postmenopausal patients scheduled to receive neoadjuvant endocrine therapy for BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-02.

Background: Darbepoetin alpha (ARA) is currently used to reduce chemotherapy-associated anemia (CAA) rates in various solid tumors. A possible negative impact of ARA on patient survival has been suggested in some clinical trials. The objective of the prospective randomized phase III ARA Plus trial is to compare the survival effect of darbepoetin alpha use (ARA+/ARA-) in combination with modern standard adjuvant chemotherapy targeting guideline-recommended Hb-levels in high-risk breast cancer (BC). Methods: ARA Plus compared 6 cycles T75A50C500 q3w or 6 cycles F500E100C500 q3w (at discretion of each center) in patients with node positive BC (aged 18–65 years). Patients were randomized to darbepoetin (ARA+) 500 μg q3w until completion of radiotherapy or to standard supportive care (ARA-). ARA was started at Hb-levels ≤13 g/dL (amendment 01/2008: Hb ≤12 g/dL) and stopped at >14 g/dL (>12 g/dL). Primary endpoint is event-free survival (EFS: relapses, death without disease evidence, second malignancy). Overall survival (OS), toxicity, Hb-levels and quality of life are secondary endpoints. Survival analysis was planned after 7 years of study duration. EFS was tested using χ2-test (α=0.05) with a statistical power of β=80% and log-rank test. Quality of life was measured using FACT questionnaires at beginning of therapy, mid, end of therapy, and at 1 year afterwards. Results: 1234 pts (616 ARA+/618 ARA-) from 70 centres in Germany were randomized between 01/04 and 06/08. 1198 intent to treat patients (ITT) were analysed (1096 TAC; 102 CEF). Baseline characteristics were well balanced in ARA+ and ARA- arms: median age 53/53 years; tumor size 2.4/2.4cm; number of + LN 3/3; HR+ 80%/ 83.5%, G3 40.7%/36.7%. Toxicity data have been reported earlier (SABCS 2008). At median follow up of 40 months, 168 events (81 ARA+, 83 ARA-) and 134 relapses (65 ARA+, 69 ARA-) were reported. There was no significant difference in 3-year EFS between ARA+ and ARA- arms (89.2% vs. 87.6%, p=0.97, χ2-test). 37 deaths were reported in the ARA- and 36 in the ARA+ arm. 3-year OS was 95.4% and 95.1% for ARA+ and ARA-, respectively (p=0.85). Only nodal involvement (≥4 vs. 1–3), negative HR, tumor size >2 cm and G3 were significant survival predictors by multivariate analysis. Unplanned retrospective analysis revealed better EFS for ARA+ vs. ARA- in HR- (p=0.05), and no difference in HR+ group (p=0.6). In ARA+ patients, Hb-levels were stable over the whole treatment period with rare overstimulation. In ARA- patients, Hb-levels decreased during therapy (median of all cycles ARA+/ARA-: 12.5/11.6 g/dL). There was no correlation between mean Hb-levels and survival in either study arm. There were no significant differences in mean FACT scores changes (general, anemia, cognitive) from begin to end of therapy in either study arm. More detailed analyses are ongoing. Conclusions: To date, the WSG ARA plus trial is the only prospectively randomized trial in early high-risk BC exclusively focusing on the impact of adjuvant ARA on patient outcome. Supportive administration of ARA appears to be safe and to have no significant survival effect when used in combination with TAC or CEF according to current guidelines. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-06.

Background: The implementation of breast centers aims at improving the quality of care for breast cancer patients. Hereby the quality of psychosocial interaction from doctors and nursing staff is an essential aspect for patient satisfaction. This presentation based on empirical data shows the quality of psychosocial interaction from the point of view of patients in 51 german breast centers and if it has changed in annual comparison. Moreover, it analyses how the individual breast centers differ from each other and gives benchmarking data as well as data concerning the increasing significance attributed by patients to the assessment of quality of care and patient satisfaction.Material and Methods: Basis for the data is a retrospective survey of 10837 newly diagnosed breast cancer patients after primary surgery between 2006 and 2008 in 51 breast centers in Germany. After being inpatients, they were sent the specially developed Cologne Patient Questionnaire for Breast Cancer (CPQ-BC) which comprises key data to relevant aspects of psychosocial interaction such as support from physicians or nursing staff, doctor facilitation scale, patient information scale, patient participation in decision making, empathic provision of information, provision of information by physicians (basic and additional information), physical functioning, psychological well-being and tendency to excuse.Results: 88% of the contacted patients returned a completed questionnaire. The results of the descriptive analyses show that the quality of psychosocial interaction in the breast centers was overall evaluated very positively and that it is relatively stable in three years time. However, there are clear differences between the individual centers.Discussion: We noted that the quality of psychosocial interaction in the german breast centers already has a high standard from the patients point of view. This standard needs to be maintained and developed further. Moreover, the declared aim should be to dismantle the existing differences in quality between the centers. A specific evaluation of various structure and process features can give information on the reasons for these differences. Benchmarking data and specially developed benchmarking workshops help breast centers and their teams to improve quality of care and provide a good psychosocially supportive provider-patient interaction. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1071.

OBJECTIVE: BRCA1/2 mutations carriers face a lifetime risk for breast cancer of 60 to 80%. Typically, tumor incidence is high at young age and tumor growth rates are significantly elevated. On ultrasound investigation the malignancies often mimic fibroadenomas with round shape, circumscribed margins and a homogeneous internal structure leading to a BIRADS 3 classification. On this background we evaluated the efficacy of ultrasound for the early detection of breast cancer in this high risk group.METHODS: Between 01/1997-07/2008 223 BRCA1/2 mutation carriers participated in a breast cancer screening program which included semi-annual ultrasound (US) and annual mammography (MG) and MR imaging (MRI).Screening procedures started from age 25, MG at age 30. As patients consecutively joint the study women underwent 5 (median) screening rounds with a range of 1 to 22 appointments, totaling 1855 rounds of screening. All three imaging modalities were coded according to the American College of Radiology (BI-RADS classification).RESULTS: We detected 15 primary and 14 secondary contralateral BRCA-associated tumors in 27 patients. Age at diagnosis ranged from 29 to 66 years (median 41 years). BI-RADS classification IV and V enabled the detection of 9 (32%) cancers by mammography, 21 (87,5%) by US and 27 (96%) by MRI scan. Specificity added up to 100%. Three (11%) tumors were detected by the semi-annual ultrasound screen and two patients presented with interval carcinomas (16 and 8 mm in diameter) between two screening appointments. Thus, the proportion of interval cancers was 7%.CONCLUSION: Semi-annual sonography as a supplementary examination enabled us to reveal 3 additional invasive cancers (two stage pT1b, one stage pT1c). Due to the specific tumor morphology and the considerably elevated tumor doubling time mutation carriers may benefit from the addition of semi-annual ultrasound as a highly sensitive and cost-effective method. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4004.

e11512 Background: Docetaxel is the most effective mono-substance in metastatic BC and highly effective in adjuvant chemotherapy. Early docetaxel-monotherapy data in primary systemic therapy (PST) showed a pCR of 18% (Amat et al; 2003), comparable with pCR-rates of standard PST combination chemotherapy. HEDON was conducted to evaluate efficacy of docetaxel ± T with regard to pCR (defined as absence of invasive and non-invasive BC in breast and lymph nodes) as primary endpoint; secondary endpoints were safety, breast conservation rate and 5-yr DFS. Additionally Trans-HEDON includes a translational research program to identify molecular RNA and methylation (DNA) based markers of response to docetaxel-monotherapy. Methods: From 2006 until 2008, the multicenter phase II HEDON trial fully recruited 93 pts, with therapy still ongoing; tumor stages: T2 (23), T3 (11), T4 (5); nodal status: N0 (16), N1–2 (23). Arm A: Docetaxel (100 mg/m2x6) in HER2-negative (n=60) and Arm B: Docetaxel (100 mg/m2x6) in combination with T (18x2mg/kg KG) preoperatively in HER2-overexpressed BC (n=33), followed by surgery and then by adjuvant epirubicin/cyclophosphamide (E90Cx4), radiotherapy if indicated, T for altogether one year, and endocrine therapy in ER+ and/or PgR+ BC. Pre-planned interim analysis (safety and efficacy) was performed after recruitment of 39 pts (Arm A 26, Arm B 13). Results: In Arm A, 7 pts. (26.9%) achieved pCR and 9 pts. (34.6%) pPR. In Arm B, 7 pts. (53.8%) achieved pCR and all 6 others (46.2%) pPR. Neutropenia occurred in 11 pts. (8 with grade 3). Moderate (25%) dose reduction was necessary in 13 pts., and 50% dose reduction in one patient. Conclusion: According to interim analysis of the HEDON trial, docetaxel-monotherapy of 6 cycles at 100mg/m2 q21 (plus T in HER2-positive BC) is an effective and safely administrable PST. There were no unexpected toxicities, and preliminary pCR rates in HER2-neg (26.9%) and HER2-pos (53.8%) pts. were comparable to those of combination chemotherapy. These interim results will be completed by final analysis on the full collective, with molecular predictors from TransHEDON hopefully identifying patients who derive extensive benefit. [Table: see text]

Abstract #4100 Background: Modern adjuvant chemotherapy regimens may cause considerable anemia. Epoetins are currently used to reduce chemotherapy-associated anemia (CAA) rates in a variety of solid tumors. The discussion of potential effects on survival rates is highly controversial. The ARA Plus trial is a prospective randomized trial comparing adjuvant chemotherapy +- darbepoetin (ARA+ / ARA-) in node-positive breast cancer patients. Methods: Inclusions criteria were: age of 18 to 65 years, positive lymph nodes (LN) after resection of >10 LN, free margins , M0 status confirmed by conventional staging. At the discretion of the investigating centre patients could receive 6 cycles T75A50C500 or 6 cycles F500E100C500) q3w. They were randomized to darbepoetin (ARA+) 500μg q3w until completion of radiotherapy or to standard supportive care. Darbepoetin was started at Hb level Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4100.

17526 Background: Breast cancer (bc) remains the most common cancer to affect women, with an incidence of 55,100 per year in Germany. Germany still does not have a register of cancer pts. This has ...

1092 Background: Fulvestrant is used in the treatment of postmenopausal women with estrogen receptor-positive, locally advanced or metastatic breast cancer. The questions of the study are whether fulvestrant is safe, effective and tolerable. Methods: 848 patients were enrolled in this fulvestrant in practice evaluation programme (IPEP). Under clinical routine conditions in the participating centers regarding selection of subjects, diagnostic procedures or therapeutic decisions, all relevant data was documented over 9 months of fulvestrant therapy in postmenopausal women with advanced ER+ breast cancer who had relapsed during or after adjuvant anti- estrogen treatment, or with disease progression under palliative anti-estrogen therapy. Results: Data of 597 (70%) of patients was evaluable according to protocol. Median age was 64 years, 52% of patients had a co-morbidity, 78% one or more prior palliative therapies. Safety: 15.6% had one or more adverse events, mainly hot flushes, gastrointestinal, or musculo...

564 Background: TAC is one of the most effective regimens. It‘s associated with higher frequency of anemia and chemotherapy-induced neutropenia (CIN). The erythropoiesis stimulating factor (ESF) support of chemotherapy, its complications and survival effect remain unclear. Erythropoetins do prevent chemotherapy-associated anemia (CAA) and subsequent fatigue syndrome but their potential influence on survival is still unclear. One aim of this analysis is to investigate the correlation between CT, growth factor support and toxicity (SAE‘s). Methods: This ARA Plus phase III trial compare chemotherapy ±ARA in breast cancer patients >18 years old, with positive lymph nodes and with M0 disease. Pts get six cycles of of 5-fluoro-uracile 500mg/m2, epirubicine 100mg/m2 and cyclophosphamide 500mg/m2, (FEC, Bonneterre), 3-weekly or six cycles of docetaxcel 75mg/m2, adriamycin 50mg/m2 and cyclophosphamide 500mg/m2, (TAC, BCIRG) and are randomized to ARA 500μg q3w if Hb No significant financial relationships to disclose.