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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.

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: Optimal treatment, particularly use of anthracyclines in aggressive triple-negative breast cancer (TNBC), is still a controversial issue in early BC management. However, TNBC exhibits substantial molecular heterogeneity: for example, the immune phenotype seems to be associated with better outcome. An important clinical issue in early TNBC is to quantify the impact of subtypes as well as individual genes on survival and especially on anthracycline benefit. Methods: In PlanB, patients with ER and PR Results: RNA expression results were available in n=394 (203 TC vs. 191 EC-Doc): PAM-50 subtype: basal-like 82%; HER2-enriched 7%; luminal (A or B) 3.5%; normal-like 7.4%. Median age was 54; 78% were node-negative. In patients with “discordant” tumors (HR positive by local or central assessment), 76% were still basal-like, compared to 86% in “concordant” TNBC. Of 27 patients with HER2-enriched subtype, HER2 status was positive by central assessment in only five cases (18%). Within this TN cohort, 5y DFS was similar in TC (83%) and EC-Doc (79%) arms; positive nodal status and tumor size >2 cm were (unfavorable) clinical-pathological prognostic markers. Prognostic or predictive impacts of molecular subtype, risk of recurrence subgroups, or proliferation indices were not seen. Twelve genes (incl. CD8, EGFR, GPR160, SPINT2) showed potential multivariate prognostic impact by entering the “forwards stepwise” multivariate Cox model for DFS. The upper half of patients according to the resulting “twelve-gene signature” had well over 90% 5y-DFS, whereas the lowest quartile had under 60% 5-y DFS. Several genes (incl. ERBB2, FOXC1) showed potential for a predictive impact regarding TC vs. EC-Doc by interaction analysis. Further details and perspectives for testing the robustness of these potential impacts will be presented at the meeting. Conclusions To our knowledge, these are the first results from a prospective, adjuvant taxane-based trial regarding molecular predictors of anthracycline efficacy and PAM-50-based prognostic factors in early TNBC. ERBB2 expression, but not HER2-enriched subtype, was predictive for A-benefit in HER2-negative BC. Molecular heterogeneity of TNBC beyond basal-like vs. non-basal-like subtype is clinically relevant and should be considered for patient stratification in ongoing trials with combination therapy. The identified prognostic gene signature should be validated in the WSG-ADAPT-TN and other TNBC trials. Citation Format: Gluz O, Liedtke C, Prat A, Christgen M, Gebauer D, Kates R, Pelz E, Clemens M, Warm M, Aktas B, Kuemmel S, Pare L, Krabisch P, Kreipe HH, Wuerstlein R, Nitz U, Harbeck N. Genomic markers but not molecular subtypes provide prognostic impact and predict anthracycline efficacy in early triple-negative breast cancer: Results from the prospective WSG PlanB trial [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 P2-10-03.

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.

Background: The GeparSepto (NCT01583426) study showed that nab-paclitaxel (nP) increases the pathological complete response (ypT0 ypN0) rate when it replaces paclitaxel (P) as part of a sequential taxane followed by epirubicin/cyclophosphamide (EC) neoadjuvant chemotherapy for pts with early breast cancer (BC) (Untch Lancet Oncol 2016). After a safety analysis showed a higher rate of dose reductions, treatment discontinuations as well as peripheral sensory neuropathy (PSN) with nP 150 mg/m2 w (nP150) compared to P 80mg/m2 w, dose of nP was reduced to 125 mg/m2 w (nP125). The risk-benefit ratio of nP125 was improved over nP150 (von Minckwitz SABCS 2015). We reported follow-up (FU) data on PSN occurrence and resolution. Methods: Pts with untreated BC received P 80mg/m2 w or nP 150/125mg/m2 w followed by four cycles of E 90 mg/m2 plus C 600 mg/m2 q3w, with trastuzumab 6 mg/kg (loading (LD) dose 8 mg/kg) and pertuzumab 420 mg (LD 840 mg) q3w if HER2+. After the end of the study the protocol was amended in order to collect long-term data on PSN outcome as well as on treatment modalities. PSN will be reported according treatment and dose received on day 1. Results: Overall 601 pts received P80; 220 pts nP150 and 385 pts nP125 on day 1. PSN grade 2-4 was observed in 18.8% (n=113/601) of pts treated with P80 and in 41.8% (n=92/220) vs 39.2% (n=151/385) with nP150 and nP125 respectively (p=0.547). Grade 3-4 PSN was reported for 2.7% (n=16/601) of pts in the P80 group and 14.5% (n=32/220) vs 8.1% (n=31/385) in the nP150 vs nP125 group respectively (p=0.018). In 31.8% (36/113), 35.9% (33/92) and 27.2% (41/151), PSN was not resolved at the end of the treatment (EOT); PSN grade 3-4 was not resolved in 37.5% (6/16), 56.3% (18/32) and 58.1% (18/31). After a median FU of 110 weeks after EOT, data on PSN status for pts with unresolved PSN grade 2-4 were available from 30, 22 and 32 pts; 26 pts did not provide update information (n=7 died, n=5 data not yet available, n=14 status unknown). For 63.3% (n=19), 40.9% (n=9) and 56.2% (n=18) of pts, PSN grade 2-4 was resolved to grade 1. Time to resolve (TTR) of PSN grade 2-4 was significantly different between nP150 and nP125 (p Conclusions: nP125 is associated with a lower occurrence of PSN compared to nP150 but higher PSN than P80. If PSN occurred nP125 is associated with a more rapid resolution compared to nP150. Nearly 10.7% had no resolution of PSN so far. Further FU and markers for selecting pts at risk are needed. The trial is supported by Celgene. Table 1. Median time to resolution (mTTR) of PSN to grade 1comparison groupsmTTR n (weeks); [95% CI]P vs nPPnP150nP125grade 2-47 [6-9]8 [6-10]grade 3-49 [4-15]17 [5-123]nP150 vs nP125 grade 2-4 13 [9-15]6 [4-9]grade 3-4 56 [11-170]17 [10-nr]abbreviations: nP, nab-paclitaxel; P, paclitaxel; nr, not reached Citation Format: Furlanetto J, von Minckwitz G, Jackisch C, Schneeweiss A, Aktas B, Denkert C, Wiebringhaus H, Kuemmel S, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer J-U, Clemens M, Costa SD, Gerber B, Nekljudova V, Untch M, Loibl S. Peripheral sensory neuropathy occurrence and resolution: Results from the neoadjuvant randomized GeparSepto study (GBG 69) [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 P5-16-03.

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.

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 P1-13-01.

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.

Einleitung: Die EvaluateTM-Studie (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor positive breast cancer patients receiving letrozole treatment) ist eine prospektive, nicht interventionelle Studie, die das Therapiemanagement und die Compliance im Rahmen der Routineversorgung unter einer Therapie mit Letrozol bei postmenopausalen Patientinnen mit einem invasiven, hormonrezeptorpositiven Mammakarzinom als Studienziel hatte. In dieser Publikation werden die Parameter bei Studieneinschluss berichtet. Material und Methoden: Von Januar 2008 bis Dezember 2009 wurden insges. 5045 Patientinnen in 310 Prufzentren in die EvaluateTM-Studie eingeschlossen. Zugelassen waren Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom in der adjuvanten und metastasierten Therapiesituation. 373 Patientinnen mussten aus unterschiedlichen Grunden aus den Analysen ausgeschlossen werden. Ergebnisse: Insgesamt wurden 4420 Patientinnen in der adjuvanten und 252 Patientinnen in der palliativen (metastasierten) Situation in die Studie eingeschlossen. Bei 4181 Patientinnen in der adjuvanten Situation wurde direkt nach operativer Therapie mit einer Aromataseinhibitortherapie mit Letrozol begonnen (upfront). Bei 200 Patientinnen wurde zunachst Tamoxifen gegeben und in den Jahren 2 – 5 nach Diagnosestellung mit der Aromatasehemmertherapie mit Letrozol begonnen (switch), und bei 39 Patientinnen erst 6 – 10 Jahren nach Diagnosestellung (extended endocrine therapy). Die Patientinnen- und Tumorcharakteristika lagen ebenso wie die Begleiterkrankungen und die Begleitmedikation im Bereich des Erwarteten. Schlussfolgerung: Die Daten der EvaluateTM-Studie werden einen guten Einblick in das Therapiemanagement von postmenopausalen Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom im Rahmen der Routineversorgung geben. Geplante Analysen beinhalten die Therapiepersistenz und die Zufriedenheit mit den Informationsstrukturen und dem Aufklarungsinhalt.

Mit einer Inzidenz von bis zu 81 % stehen Serome an der Spitze postoperativer Nebenwirkungen. Jedoch werden nur ca. 15 % durch Folgekomplikationen wie Infektionen und sekundare Wundheilungsstorungen zum klinisch relevanten Problem. Die Entstehung von Seromen ist multifaktoriell, basiert auf der Reaktion auf mechanische und thermische Gewebezerstorung, verstarkt durch exsudativ-(pro)inflammatorische Prozesse, und ist eng mit dem entstandenen „Totraum“ im Wundgebiet verknupft. Der Umfang des operativen Eingriffs im Bereich der Brust und Axilla ist nur bedingt fur die Serombildung verantwortlich. Die Untersuchungen einer Vielzahl von hypothetischen Risikofaktoren zeigten keine konklusiven Resultate. Eine Vielzahl von Serom-minimierenden Verfahren wurde untersucht. Fibrin-basierte Gewebeklebstoffe fuhrten nicht zu relevanten Verbesserungen. Die Art und Weise der Gewebedissektion wurde in einigen Untersuchungen als beeinflussender Faktor identifiziert. Einzig die Verminderung des Totraums der Wundhohle durch innere Nahte fuhrt bisher zu signifikanter Seromminderung mit den Nachteilen der Operationszeitverlangerung und der Ausbildung innerer Narben. Die Drainierung von Wunden ist Behandlungsstandard, der jedoch nicht unumstritten ist. Erste positive Erfahrungen wurden mit einem Urethan-basierten Gewebeklebstoff gemacht, der zur chemisch-mechanischen Verkleinerung des Wundtotraums mit oder ohne Verwendung von Drainagen fuhrt. Prospektive Studien, die zur Identifizierung der effektivsten Strategie fuhren sollen, sind in der Planung.

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.

Background Oncotype DX® has become part of clinical routine in the diagnosis and decision-making progress in early breast cancer (EBC). Prospective data on its clinical use and impact on treatment decisions in ER-positive (ER+) node negative (N0) disease from various controlled clinical trials in different countries have been published recently. The Recurrence Score® (RS) has also been validated as a prognostic and predictive marker for patients with ER+ node positive (N+) disease. As of today no prospective data have been reported on its impact on decision making in these patients. We performed a large prospective study to evaluate RS-guided adjuvant therapy in N0 and N+ ER+ EBC. Material and Methods: Patients (pts) with ER+, HER2−negative N0 and N+ (1-3 positive lymph nodes) EBC and no contraindication for adjuvant chemotherapy were included in the study. Physicians’ adjuvant treatment recommendations and their confidence in these as well as patients’ decisional conflicts were assessed before and after knowledge of the results of the test using standardized questionnaires. Actual treatment data were collected to perform pharmacoeconomic analyses. Analyses were performed on the per-protocol population for whom a Recurrence Score result and treatment recommendations pre and post-test were available. Results: Overall 379 pts were recruited. In 11 pts Oncotype DX could not be performed and 2 pts dropped out leaving 366 pts in the per protocol population. Of these, 244 (66.7%) were N0 and 122 (33.3%) N+. Median age was 56 years (Range 25–85). Overall, 54.1% had low, 38.0% intermediate and 7.9% high RS values. For N0 disease, the distribution of RSs was 53.7%, 38.9%, 7.4% and for N+ disease 54.9%, 36.9% and 9.0%, respectively. Initial treatment recommendation changed in 33.1% of all cases; 30.3% in N0 and 38.5% in N+ disease, and in 36.4% for pts with low, 30.9% with intermediate and 20.7% with high RSs. In 21.6% of all pts a recommendation for adjuvant chemoendocrine therapy (CHT) was changed to endocrine therapy (HT), 10.7% of recommendations changed from HT to CHT. For N0 disease change rates were 18.4% from CHT to HT and 11.5% from HT to CHT. For N+ disease 27.9% of recommendations changed from CHT to HT and 9.0% of recommendations changed from HT to CHT. In 25% of all, 22% of N0 and 39% of N+ pts initially recommended HT the post-RS recommendation changed to CHT; in 38% of all, 39% of N0 and 37% of N+ pts initially recommended CHT the recommendation changed to HT. Overall, physicians’ confidence increased in 45.1% of all (p=0.047) and 44.7 of N0 and 45.9% of N+ cases, respectively. There was a moderate decrease of the decisional conflict score in all pts and subgroups that reached statistical significance for all pts (p=0.029) and the low RS subgroup (p=0.003). Conclusions: Results of this large prospective study show an impact of the RS on adjuvant treatment decision making in German clinical practice for patients with ER+ EBC. Recommendations were predominantly changed from chemoendocrine to endocrine adjuvant therapy resulting in a net reduction of chemotherapy usage. This effect was more pronounced for patients with 1–3 positive nodes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-26.

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 ...

The patient-reported assessment of physician empathy can be indicated for outcome research, at interventions and in medical practice. The aim of this investigation is the evaluation of the psychometric properties of the German version of the "Consultation and Relational Empathy" (CARE) measure on the example of inpatient cancer patients (N = 326). The one-dimensional structure of the instrument can be replicated by a confirmatorical factor analysis. Hypothesis-consistent relationships to different patient and physician factors as well as to socio-demographic and illness-particular features of the patients can be shown. In medical practice the CARE-scale can be used by the physician e. g. as a time-economic feedback instrument for the evaluation of strengths and weaknesses of their empathic behaviour, as a personal behaviour checklist within a consultation and/or as a checklist to determine patient preferences before/during a consultation.

Objective The aim of the present cross-sectional study was to explore patient- and physician-specific determinants of physician empathy (PE) and to analyse the influence of PE on patient-reported long-term outcomes in German cancer patients. Methods A postal survey was administered to 710 cancer patients, who had been inpatients at the University Hospital Cologne (response rate 49.5%). PE was measured with the German translation of the consultation and relational empathy (CARE) measure, and patient-reported long-term outcomes were assessed using the major (ICD-10) depression inventory (MDI) and the EORTC quality of life (Qol) questionnaire QLQ-C30. Hypotheses were tested by structural equation modelling. Results PE had (a) a moderate indirect effect on “depression” and a smaller indirect effect on “socio-emotional-cognitive Qol” by affecting “desire for more information from the physician regarding findings and treatment options” and (b) a moderate indirect effect on “socio-emotional-cognitive Qol” and a smaller effect on “depression” via “desire for more information about health promotion”. The determinant with the greatest importance was “patient-perceived general busyness of hospital staff”: it had a strong negative influence on PE, indirectly influencing “desire for more information from the physician regarding findings and treatment options” and also patients’ “depression”. Conclusion PE seems to be an important pre-requisite for information giving by physicians and through this pathway having a preventive effect on depression and improving Qol. Conversely, physicians’ stress negatively influences these relationships. Practice implications The research findings suggest that reducing physicians’ stress at the organizational and individual may be required to enhance patient–physician communication. Empathy, as an outcome-relevant professional competence needs to be assessed and developed more intensively in medical students and physicians.

PURPOSE: Retrospective analysis of the success and complication rates of chest port implantation via the lateral subclavian vein. MATERIALS AND METHODS: Between January 2003 and June 2004, the lateral subclavian vein in 271 patients (186 women, 85 men, mean age 53.2 years) was punctured guided by ultrasound. This access was used to insert a port system, and the catheter tip was placed at the cavoatrial junction. The port reservoir was implanted in a subcutaneous infraclavicular pocket and fixed to the fascia of the pectoralis muscle. Indications for port implantation were chemotherapy (n = 239), total parenteral nutrition (n = 2) and intravenous medication (n = 30). The patient follow-up was mainly performed either by the oncology division of the department of gynecology or by the department of internal medicine. RESULTS: A chest port catheter system was successfully implanted in all patients. The catheter remained in place for a mean duration of 269.4 days (SD 192.3 days). No complications occurred during implantation. In the post-interventional period, 6 catheter dysfunctions were found (thrombotic 0.09 per 1000 catheter days; mechanic 0.05 per 1000 catheter days). While one local infection occurred in the early post-interventional period, 3 local and 15 systemic infections were independent of the port catheter placement (0.39 per 1000 catheter days). The rate of port catheter ex-plantation due to dysfunction or infection was 0.07 per 1000 catheter days. CONCLUSION: Ultrasound-guided puncture of the lateral subclavian vein is a safe procedure for the insertion of central venous port catheter systems and had a very low complication rate in our study. For further evaluation of our port placement technique, prospective studies compared to placement through the internal jugular vein are necessary.

PURPOSE To compare the image quality of digital X-ray mammographies obtained with wet imagers with that of standard dry imaging technology. MATERIAL AND METHODS Beginning 03/08/2003, 200 X-ray mammographies with a digital fullfield mammography system (Lorad Selenia, Lorad/Hologic) were prospectively and consecutively documented with a wet laser imager (Scopix LR 5200, Agfa), a dry infrared laser imager (DryView 8610, Kodak) and a dry imager using the principle of direct thermography (Drystar 4500M, Agfa, N = 166). One X-ray exposure was systematically chosen from each examination and was presented in an anonymous and randomized form to three radiologists who evaluated the films using a structured questionnaire. RESULTS The visualization of normal anatomic structures was considered being good to excellent for all imagers with the mean assessments 1.0 - 2.4 for the Drystar 4500M, 1.0 - 2.1 for the DryView 8610 and 1.1 - 2.0 for the Scopix LR 5200. The mean assessments were 0.1 - 0.6 points lower in dense than in normal parenchyma, thus, the parenchymal density is the predominant factor for image quality. CONCLUSION In view of the comparable image quality obtained with the different imagers used in the study, individual decisions to purchase a specific imager will be based on economics rather than on diagnostic points of view.

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.