Ronald Kates

REK Consulting

Background: In high-risk HR+/HER2- early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy vs solvent-based (sb)-paclitaxel in neoadjuvant trials, however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX Recurrence Score (RS) and e...

Micro-mobility modes such as e scooters are gaining increasing popularity, but e-scooter riders have high crash/injury risks. Virtual assessment of traffic safety measures, such as automated driving functions, requires valid models of all road users, including their interactions and responses to threats. This paper focuses on process models of thre...

Background The association of early changes in the immune infiltrate during neoadjuvant chemotherapy (NACT) with pathological complete response (pCR) in triple-negative breast cancer (TNBC) remains unexplored. Methods Multiplexed immunohistochemistry was performed in matched tumor biopsies obtained at baseline and after 3 weeks of NACT from 66 pat...

Background: Pathological complete response (pCR) is associated with improved outcome in patients with high-risk HR+/HER2- breast cancer (BC) but the use of (neo)adjuvant chemotherapy in early HR+/HER2- BC remains controversial. Oncotype DX / Recurrence Score (RS) and dynamic Ki67 response after short preoperative endocrine therapy are potentially p...

Background: In HR+/HER2- N0 early breast cancer (EBC), patients (pts) with Recurrence Score™ (RS)<26 (postmenopausal) and <16 (premenopausal) have excellent prognosis and do not benefit fromadditional chemotherapy. However, prognostic impact of RS in N+ disease and importance of Ki67response after short preoperative endocrine therapy (ET) in the co...

Goals: The WSG ADAPT trial program is one of the first new generation trials addressing the issue of individualization of (neo)-adjuvant decision-making in early breast cancer (EBC) in a subtype-specific manner. The first WSG ADAPT umbrella trial (NCT01779206) aimed to establish early predictive molecular surrogate markers for response after a shor...

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 plann...

Many patients with ER+ HER2− primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical endocrine therapy in order to provide guidance on the identification of patients who may have insufficiently endocrine-sensi...

Background Endocrine sensitivity, as determined by response of the proliferation marker Ki-67 to short-term preoperative endocrine therapy (ET), is currently not included in adjuvant treatment decisions in hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). Methods The prospective WSG-ADAPT HR+/HER2− trial i...

The introduction of micro-mobility, such as e-scooters, brings new challenges. Nevertheless, these trend devices are spreading rapidly without a comprehensive study of their interactions with other road users. For example, many countries currently require drivers of e-scooters to signal turns by hand. In this work, we investigate whether e-scoot...

Background Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had...

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the...

515 Background: HR+/HER2+ breast cancer (BC) is a distinct entity associated with better prognosis compared to HR-/HER2+ BC. However, combination of chemotherapy (CT) with (dual) anti-HER2 blockade is standard in HER2+ early BC (EBC), irrespective of HR-status. Despite of some promising data on combination of endocrine therapy (ET) with dual anti-H...

2083 Background: PreCycle (NCT03220178), a multicenter, randomized phase IV Intergroup trial evaluates the impact of ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer patients (pts) treated by palbociclib (P) and an aromatase inhibitor or P+fulvestrant. Pts willing to use the web/APP-eHealth solution...

TPS601 Background: The WSG ADAPT trial program represents the concept of individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. The first WSG ADAPT umbrella trial aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment. The goals of the WSG ADAPT trial p...

Background: The presence of tumor-infiltrating lymphocytes has been associated with prognosis and chemotherapy response, particularly in high-risk breast cancer subtypes. There is limited data so far as to (i) how tumor-infiltrating lymphocyte (TIL) measurements correlate with genomic measurements such as the Oncotype DX Recurrence Score® and (ii)...

Background: Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). Patients and methods: Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients fo...

Background: Efficacy and quality of life (QoL) are key factors when selecting therapies for metastatic breast cancer (MBC) patients. The addition of targeted oral agents such as CDK4/6 inhibitors to endocrine therapy is the new standard for hormone receptor (HR)+ HER2- MBC and substantially prolongs progression-free survival. However more complex o...

Background: Among patients with highly heterogeneous HER2+ breast cancer (BC), pathological complete response (pCR) (ypT0/is/ypN0) is associated with improved prognosis. The prospective, phase-II neoadjuvant 3-arm WSG (ADAPT-TP) showed pCR rates of about 41.0% after 4xT-DM1+/-ET and 15% after trastuzumab+ET. Pre-planned translational analysis of AD...

Introduction: More than 1/3 of early breast cancers (EBC) are diagnosed in women ≥ 70 years. Although polychemotherapy has been shown to be more effective than monochemotherapy also in these patients, only limited prospective data on efficacy of neoadjuvant therapy are available so far. Here, we present results of the prospective ADAPT Elderly sub-...

Purpose: Only limited data are available on predictive markers for use of chemotherapy-free, anti-HER2 combinations in HER2-positive early breast cancer (eBC), in particular within the molecularly distinct HER2+/HR- subgroup. Background: In the ADAPT HER2+/HR- trial, a promising pCR of about 43-45% was found in patients treated by 4 cycles of pertu...

Background Efficacy and quality of life (QoL) are key factors when selecting therapies for metastatic breast cancer (MBC) patients. The addition of targeted oral agents such as CDK4/6 inhibitors to endocrine therapy is the new standard for HR+ HER2- MBC and substantially prolongs progression-free survival. However more complex oral medication in on...

This paper focusses on the role of driver individuality in the field of cognitive driver behavior modeling for the prospective safety impact assessment of advanced driver assistance systems (ADAS) and automated driving functions. Virtual traffic simulation requires valid models for the environment, the vehicle and the driver. Especially modeling hu...

In the neoadjuvant WSG‐ADAPT‐TN trial, 12‐week nab‐paclitaxel + carboplatin (nab‐pac/carbo) was highly effective and superior to nab‐paclitaxel + gemcitabine (nab‐pac/gem) in triple‐negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients recei...

Purpose The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer. Methods 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therap...

TPS596 Background: WSG (West German Study Group)-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, controlled (neo)adjuvant, non-blinded, randomized phase III trial (EudraCT 2018-003749-40). It investigates whether HR+/HER2- intermediate-risk patients (pts) (about 20 % of HR+/HER2- early breast cancer, EBC) identified...

The article Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial, written by Ulrike Nitz, Oleg Gluz, Matthias Christgen, Ronald E. Kates, Michael Clemens, Wolfram Malter, Benno Nuding, Bahriy...

Purpose: The West German Study Group PlanB trial evaluated an anthracycline-free chemotherapy standard (six cycles of docetaxel and cyclophosphamide [TC]) in the routine treatment of human epidermal growth factor receptor 2-negative early breast cancer (EBC). Patients and methods: Patients with pT1 to pT4c, all pN+, and pN0/high-risk EBC were el...

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 TN...

Background: Elderly breast cancer (BC) patients (pts) have been reported to have worse BC-related outcome than younger pts, even within clinical trials such as TEAM. Shak et al. recently showed in a large SEER data analysis that in the high 21-gene recurrence score (RS) group, older pts (>70y) receive less chemotherapy (CT) and have a worse BC-spec...

This abstract was withdrawn by the authors.

Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). The optimal chemotherapy regimen is unclear. Weekly nab-paclitaxel vs conventional paclitaxel or addition of carboplatin to anthracycline-taxane results in higher pCR rates with uncertain survival impact. We evaluated car...

Background: The prospective phase 3 PlanB trial used the Oncotype DX(®) Recurrence Score(®) (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other tr...

Transcription factor AP-2β (TFAP2B) regulates embryonic organ development and is overexpressed in alveolar rhabdomyosarcoma, a rare childhood malignancy. Gene expression profiling has implicated AP-2β in breast cancer (BC). This study characterizes AP-2β expression in the mammary gland and in BC. AP-2β protein expression was assessed in the normal...

Background Data on the value of digital breast tomosynthesis (DBT) for further assessment of screen-detected lesions are still limited. Purpose To compare screening mammography, single-view DBT and ultrasound-information (TS) vs. screening mammography, additional views and ultrasound-information (AV) for assessment of screen-detected abnormalities...

Purpose Human epidermal growth factor receptor 2 (HER2)–positive/hormone receptor (HR)–positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or wi...

Background: Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (...

Advanced driver assistance and automated driving can influence traffic safety in a variety of ways. The development and implementation of safety-relevant functions require prospective, quantitative assessment of their traffic safety impacts. Both benefits and risks can be quantified using simulation-based virtual experimental techniques. To this en...

504 Background: Optimal chemotherapy in HER2-negative, particularly HR-positive, early breast cancer (EBC), especially the survival impact of anthracyclines, is still a matter of debate. Retrospective analyses saw most benefit of 6xCEF vs. 6xCMF in HER2+ EBC. Prospective trials have shown conflicting results; no predictive molecular factors have be...

573 Background: In the ADAPT-TN neoadjuvant trial, 12-week nab-paclitaxel (nab- pac)+carboplatin (carbo) was highly effective and superior to nab-pac+gemcitabine (gem). However, within TNBC, reliable predictive markers for carbo use have yet to be identified. Methods: Patients with early TNBC (centrally confirmed) were treated by nab-pac 125 mg/m2...

582 Background: Trastuzumab (T) and Lapatinib (L) containing neoadjuvant chemotherapy (NACT) increases pathological complete response (pCR) (vs. T or nihil) in HER2+ early breast cancer (EBC). Early clinical response markers (e.g. Ki67) in a 3-week biopsy or in residual tumor correlate with therapy efficacy and risk of relapse. This WSG Neo-Predict...

Background: In luminal early breast cancer (EBC) with limited nodal involvement, current guidelines recommend to use multigene assays in addition to conventional clinicopathological factors for decision making regarding adjuvant chemotherapy (CT). The WSG PRIME Study prospectively evaluated the impact of the 70-gene signature (MammaPrint®) and the...

Background: Immune and apoptosis biomarkers are potential prognostic/predictive markers in HER2+ EBC. High PD-L1 expression was shown to be predictive for lower pCR after chemotherapy+trastuzumab+/-pertuzumab, particularly in HER2+, ER- disease. Yet, HER2+ EBC co-expressing hormone receptors is a distinct entity. The ADAPT HER2+/HR+ phase II trial...

Zielsetzung: AR und FOXA1 sind mit einer besseren Prognose assoziiert und konnten Angriffspunkte fur zielgerichtete Therapeutika darstellen. Diese Studie untersucht den Einfluss beider Biomarker auf das 5-Jahres-erkrankungsfreie-Uberleben (EFS) am homogenen Patientenkollektiv der WSG-PlanB-Studie. Zwischen 2009 – 2011 wurden 3198 Brustkrebspatienti...

This study investigated the cost effectiveness of guideline-recommended (American Society of Clinical Oncology, European Society of Medical Oncology) urokinase plasminogen activator (uPA)/plasminogen activator inhibitor-1 (PAI-1) biomarkers to guide adjuvant chemotherapy decisions for hormone receptor-positive, node-negative early breast cancer pat...

Fragestellung: Der 21-Gen Recurrence-Score (RS), Lymphknotenstatus, Grading, und immunhistochemische Marker werden fur die Chemotherapie (CT)-Entscheidungsfindung beim HR+/HER2-negativen Brustkrebs im Fruhstadium empfohlen. Die PlanB-Studie verwendete prospektiv den RS, um eine Niedrigrisikogruppe bei erhohtem klinischem Risiko anhand der klassisch...

Hintergrund: Die Verwendung von wochentlichem nab-Paclitaxel und auch die Zugabe von Carboplatin in der neoadjuvanten Chemotherapie fuhren zu einer Erhohung der pCR Raten bei TNBC. Die ADAPT-Studie vergleicht die Hinzugabe von Carboplatin vs. Gemcitabin zum Nab-Paclitaxel als ein kurzes 12-Wochen-Anthrazyklin-freies Regime. Ferner wird die Wirksamk...

Einleitung: Das HER2+ hormonrezeptor (HR)-positive primare Mammakarzinom (EBC) ist ein separater Subtyp. Die pCR Raten nach neoadjuvanter Chemo- + anti-HER2 Therapie unterscheiden sich von der HER2+ HR- Erkrankung. Vergleichende Daten zur Wirksamkeit der einzelnen Systemtherapien gibt es bisher noch nicht. Methodik: ADAPT HER2+/HR+ wurde im Januar...

Purpose: The WSG BCIST study was designed to assess the influence of Prosigna results, on physicians' adjuvant treatment recommendations by determining the extent of change in pre-test treatment recommendations following assay results. Secondary objectives were to assess the influence of Prosigna results on physicians' confidence in their therapeu...

BRCA1 is an important protein in the repair of DNA double strand breaks, which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose (HD) and tandem HD double strand break inducing chemotherap...

Purpose: The 21-gene Recurrence Score (RS) assay is a validated prognostic/predictive tool in early hormone receptor-positive breast cancer (BC); however, only a few prospective outcome results have been available so far. In the phase III PlanB trial, RS was prospectively used to define a subset of patients who received only endocrine therapy. We...

Introduction Potential prognostic and predictive markers in early, intermediate-risk breast cancer (BC) include histological grade, Ki-67, genomic signatures, e.g. genomic grade index (GGI), and intrinsic subtypes. Their prognostic/predictive impact in hormone receptor (HR: ER and/or PR) positive/HER2− BC is controversial. WSG-AGO EC-Doc demonstrat...

Background: Prosigna is a standardized test measuring expression levels of 50 classifier genes (PAM50) in breast tumor tissue using nCounter® Technology (Nanostring Technologies, Inc.). It provides intrinsic subtype and risk of recurrence (ROR) score predicting 10-year recurrence probability. WSG prospectively evaluated Prosigna's impact on therapy...

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...

Introduction: Tumor-infiltrating lymphocytes (TILs) have been associated with prognosis and with chemotherapy response among patients with BC, particularly in presence of high-risk features. The WSG planB trial randomized 2448 patients with HER2- N0/1 BC for comparison of anthracycline-free (6xTC) vs. standard anthracycline-taxane chemotherapy (4xE...

Background: In HER2+ early breast cancer (eBC) pCR rates after standard neoadjuvant chemo- + anti-HER2 therapy differ according to hormone-receptor (HR) status. Molecular analysis reveals HER2+/HR+ BC as a distinct entity within HER2+ BC. The ADAPT HER2+/HR+ phase II trial aims to identify early responders to endocrine + anti-HER2 therapy. Methods:...

The purpose of this study was to evaluate the influence of guideline-based prospective use of uPA/PAI-1 on clinical outcome in an intermediate-risk cohort of breast cancer patients. We analyzed 381 consecutive primary breast cancer patients (2003-2011) at the breast center Ostbayern meeting the following criteria: M0/N0/estrogen receptor (ER)+/G2....

Advanced driver assistance and automated driving can influence traffic safety in a variety of ways. Development and implementation of safety-relevant functions require prospective, quantitative assessment of their traffic safety impacts. Both benefits and risks can be quantified using simulation-based virtual experimental techniques. To this end, t...

Background: Prosigna is a standardized test measuring expression levels of 50 classifier genes (PAM50) in formalin-fixed, paraffin-embedded (FFPE) breast tumor tissue using nCounter Technology (NanoString Technologies, Inc., Seattle, WA). It provides intrinsic subtype and risk of recurrence (ROR) score predicting 10y recurrence probability. It was...