GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Pathological complete response rate and survival in patients with BRCA -associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: Translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242).
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 579-579
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 579-579
    Abstract: 579 Background: The phase II trial WSG-ADAPT TN randomized triple-negative breast cancer (TNBC) patients to receive 12 weeks of neoadjuvant nab-paclitaxel (nab-pac) combined with carboplatin (carbo) vs gemcitabine (gem) and showed a substantial improvement of pathological complete response (pCR: ypT0/is, ypN0) with carbo (45.9% vs 28.7%). pCR had a strong favorable impact on iDFS after 3-year follow-up. Distribution of tumor mutations in BC-associated genes and impact of BRCA mutation status on pCR and outcome are analyzed here. Methods: NGS-based mutational analysis of BRCA1/2 and 18 further (potentially) BC-associated genes was performed on DNA derived from pretreatment FFPE samples (gem: n = 158, carbo: n = 108) using a customized gene panel. Variants with a variant fraction of ≥5% were included and classified according to IARC and ENIGMA guidelines. Results: In 42 of the 266 analyzed samples, at least one deleterious BRCA1/2-variant was found (15.8%; BRCA1 n = 37, BRCA2 n = 3, BRCA1+ BRCA2 n = 2) one of which displayed an additional STK11-mutation. In the BRCA1/2-negative cohort, a mutation in one of 14 further analyzed (potential) BC-risk genes was found in 19 samples (7.1%; BARD1 n = 3, CHEK2 n = 2, CDH1 n = 2, FANCM n = 3, PALB2 n = 5, RAD50 n = 1, RAD51C n = 1, RAD51D n = 1, XRCC2 n = 1; no deleterious mutations were found in ATM, BRIP1, MRE11A, NBN). At least one deleterious variant in TP53, PIK3CA, PTEN or MAP3K1 was seen in 89.1% (n = 237; TP53 n = 233, PIK3CA n = 22 PTEN n = 15, MAP3K1 n = 1). In 22 samples (8.3%) no deleterious mutation was identified in the analyzed genes. Overall, patients with tumor BRCA mutation (carbo n = 14, gem n = 28) had 45.2% vs 34.4% pCR (OR = 1.58, 95%-CI: 0.81-3.07, p =.18) without a mutation. pCR in the small group with mutation receiving carbo (n = 14) was 64.3% vs. 34.5% in all others (OR = 3.41, 95%-CI: 1.11-10.50; p =.03); direct comparison to BRCA-positive patients receiving gem (n = 28, 35.7%, OR = 3.2, 95%-CI: 0.85-12.36, p = 0.079) did not reach statistical significance. The results suggest that the strong favorable impact of pCR on iDFS is preserved even among BRCA-positive patients (n = 42, p =.07), as well as in the BRCA-negative subgroup (p 〈 .001). No evidence for a predictive impact of BRCA mutation on efficacy of 4xEC additional chemotherapy was seen overall or within pCR subgroups. Conclusions: Twelve weeks of neoadjuvant nab-pac/carbo is a highly effective anthracycline-free regimen that leads to an excellent pCR-rate of 64% in tumor BRCA1/2-mutated cases. BRC A1/2 mutation status could support this de-escalation strategy in early TNBC, but further prospective validation of survival impacts in larger cohorts and with longer follow up is needed. More detailed survival analyses will be presented at the meeting. Clinical trial information: NCT01815242.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.579
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Concordance and clinical impact of ER, PR, HER2 expression by local and central immunohistochemistry versus RT-PCR in HR+/HER2- early breast cancer (EBC): Results from the ADAPT trial.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 536-536
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 536-536
    Abstract: 536 Background: We evaluated concordance of ER, PR and HER2 status between local, central, and RT-PCR/mRNA assessments and its clinical impact in the ADAPT trial collective in HR+ HER2- EBC (NCT01779206). Particularly, validity of borderline ER-positivity (expression level 1-10%) has great clinical relevance as treatment concepts between luminal-like and triple negative (TNBC) EBC differ substantially. Methods: Patients (pts) with clinically high-risk HR+/HER2- EBC (ER and/or PR 〉 1%) were initially treated by 3 (+/-1) weeks of endocrine therapy (ET) before surgery or sequential core biopsy (CB) and then allocated to an ET-alone or chemotherapy (ET) trial, depending on risk and endocrine response. OncotypeDX (incl. RT-PCR for ER, PR, HER2) and central IHC for ER, PR, HER2 were performed on the initial 1.CB. ER-low cohort was defined as 1-10% expression by local OR central lab (ASCO-CAP). Cox models were used to estimate hazard ratios. Results: In ADAPT, 5149 pts from 81 centers in Germany with locally ER and/or PR positive (known quantitative levels) EBC were screened 2012-2018. Median follow-up was 59 months. For ER (positive vs. negative), overall concordance measured as agreement (κ) was high between all three assessments: Local vs. central IHC: 99.3% (κ = 0.45), RT-PCR vs. central IHC: 99% (κ = 0.48). Concordance was lower for PR: RT-PCR vs. central IHC: 90.5% (κ = 0.58), local vs. central IHC: 93.1% (κ = 0.56). 3% were centrally found as HER2+ in 1.CB (73% of them were negative by RT-PCR) and/or 2. Sample. Regarding HER2-low status (1+ or 2+ but ISH negative), concordance between local and central IHC was only 53.8% (κ = 0.09). Of all pts, only 2% (n=109; n=85 with both measurements available) had low ER expression (1-10%) by either local or central pathology. Only 9 of them were concordantly identified as ER-low (11%); 8/58 (14%) ER-low by local lab had TNBC by central lab. 17/47 ER-low cases (36.2%) with known post-endocrine Ki67post had Ki67post 〈 10% vs. 59.7% in ER 〉 10%. 41.8% of ER-low cases had RS 〈 25 vs. 76.7% in ER 〉 10%. All cases with ER 〈 10% by both assessments and those with Ki-67≥40% had RS 〉 25. We observed worse iDFS (HR 1.91, p=0.034) in the ER-low group vs. ER 〉 10%. Conclusions: Although we have confirmed high agreement between local and central IHC and RT-PCR for ER, PR, HER2 assessment in locally HR+/HER2- EBC, there are still a few clinically relevant discordances. Regarding HER2-low status, standardization and quality assurance are needed if this becomes clinically relevant. Treatment of the heterogeneous ER-low group as TNBC appears reasonable only if “ER-low” is confirmed by a second assessment and in cases with Ki-67 〉 40%. Preoperative ET response assessment may be helpful if an endocrine-based therapy concept is intended. Clinical trial information: NCT01779206.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.536
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    ADAPTlate: A randomized, controlled, open-label, phase III trial on adjuvant dynamic marker—Adjusted personalized therapy comparing abemaciclib combined with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy in (clinical or genomic) high-risk, HR+/HER2- early breast cancer.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS598-TPS598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS598-TPS598
    Abstract: TPS598 Background: The WSG ADAPT trial program addresses the individualization of (neo)adj. decision-making in EBC. The ADAPT umbrella trial established early predictive molecular surrogate markers for response after a 3-wk endocrine treatment (ET) to omit chemotherapy (CT) in a cohort of early high-risk HR+/HER2- pts. ADAPTlate seeks to improve adj. therapy for pts. at high risk for late disease recurrence, who completed definite locoregional therapy (with / without (neo-)adj. CT) and are under adj. ET. This high-risk population does not derive optimal benefit from standard ET, develops secondary ET resistance, and late recurrences. Methods: Prospective, multi-center, interventional, two-arm, open, randomized, controlled adj. phase III trial (NCT04565054) to investigate additional benefit from 2 years of the CDK4/6-inhibitor abemaciclib combined with ET compared to ET alone in pts. with high-risk HR+/HER2- EBC. Abemaciclib demonstrated to improve outcome in metastatic BC and even in EBC when given as part of primary therapy. Primary objective is to demonstrate superiority of iDFS of abemaciclib + ET vs. standard ET. Secondary objectives include OS, dDFS, occurrence of CNS metastases, QoL, and translational research. Recruitment started in 9/2020 to screen 1250 pts. and to randomize 903 pts. in a ratio 3:2. Until date of submission, 33 pts. were screened and 22 randomized. Pre-/postmenopausal pts. with histologically confirmed invasive HR+/HER2- EBC, 2-6 y after primary diagnosis, with either known high clinical risk (c/pN 2-3 OR high CTS score in pN 0-1 OR non-pCR after neoadj. CT in cN 1 or G3 tumors OR G3 and Ki-67 ≥ 40% in pN 0-1) or known high genomic risk (RS 〉 25 in c/pN 0, RS 〉 18 in c/pN 1 OR high risk Prosigna, EPclin or Mammaprint in pN 0-1) or intermediate clinical, but unknown genomic risk (luminal B-like (G3 or Ki-67 ≥20%) in c/pN 0-1 AND either RS 〉 25 in c/pN 0 or RS 〉 18 in c/p N1 in screening) will be eligible. Treatment duration is 2 years for the abemaciclib + ET (premenopausal: AI + GnRH) arm, followed by at least 3-6 years ET alone. Pts. in control arm will receive 5-8-years ET at investigator´s choice. ePROs are collected using CANKADO. Translational analyses: Exploratory tissue biomarker research to assess alterations in molecular markers. Liquid biopsies (CTC/ctDNA/ctRNA) will be assessed for mutations and gene expression relevant for HR+/HER2- EBC using an appropriate technology at time of testing. Conclusions: ADAPTlate seeks to evaluate whether Abemaciclib + ET is superior to ET alone in pts. with clinical or genomic high-risk EBC even 2-6 years after initial diagnosis. Translational research aims at assessing potential mechanisms of resistance to endocrine and/or CDK4/6 targeted therapy. Clinical trial information: NCT04565054.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Gene expression signatures, stromal tumor infiltrating lymphocytes (sTILs), and change in tumor cellularity to predict pathological complete response (pCR) after 12 week de-escalated neoadjuvant endocrine therapy (ET) vs paclitaxel + dual HER2 blockade in the WSG-TP-II trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 519-519
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 519-519
    Abstract: 519 Background: There are limited data on predictive biomarkers for de-escalated ET or chemotherapy with dual anti-HER2 blockade in HR+/HER2+ early breast cancer (BC). In this translational pre-planned project of the WSG-TP-II phase II-trial (NCT03272477), we aimed to identify associations of gene expression signatures and sTILs with pCR. Methods: Patients with cT1c-cT4c, cN0-3 centrally confirmed HR+/HER2+ BC were randomized to 12 weeks of standard ET (n = 100) or paclitaxel (Pac; n = 107). All patients received trastuzumab + pertuzumab (T+P) q3w as neoadjuvant and adjuvant treatment. Gene expression signatures were analyzed using NanoString BC360 panel in baseline biopsies (T+P+ET: n = 72; T+P+Pac: n = 78). sTILs were analyzed in 93 (T+P+ET) and 97 patients (T+P+Pac) at baseline and in 65 (T+P+ET) and 57 patients (T+P+Pac) at week 3. Impacts of standardized BC360 gene expression signatures and sTILs on pCR (ypT0/is ypN0; primary endpoint) expressed in odds ratios (OR) were estimated by logistic regression analysis. Results: pCR rate in patients with BC360 analysis was 39.3% (T+P+ET: 23.6%; T+P+Pac: 53.9%). Overall, ERBB2 (OR 2.37; 95%CI 1.55, 3.62) and cytotoxic cells signature (OR 1.42; 95%CI 1.02, 1.99) were favorable for pCR, while apoptosis (OR 0.64; 95%CI 0.44, 0.92), estrogen receptor 1 (OR 0.60; 95%CI 0.42, 0.85), estrogen receptor signaling (OR 0.64; 95%CI 0.45, 0.91), and progesterone receptor (OR 0.67; 95%CI 0.47, 0.94) signatures were unfavorable. Analyzing by treatment arm, a similar pattern was observed in the T+P+Pac arm (ERBB2: OR 2.01; apoptosis: OR 0.59; estrogen- and progesterone-related signatures: OR 0.41-0.58), but not in the T+P+ET arm where only ERBB2 was prognostic for pCR (OR 7.24; 95%CI 2.12, 24.05). Baseline ≥30% sTIL levels (vs 〈 30% sTILs; n = 16 vs n = 174) were associated with pCR (OR 5.16; 95%CI 1.60, 16.66); significance was not achieved in either trial arm. Compared to 〈 30% sTILs (n = 90), low tumor cellularity at week 3 precluding sTILs analysis ( 〈 500 invasive tumor cells, n = 22), but not ≥30% sTILs (n = 10), was prognostic for pCR in all patients (OR 9.47; 95%CI 2.94, 30.50) and in individual trial arms (OR 6.00-11.79). Conclusions: This hypothesis-generating translational results suggest that gene expression signatures (particularly ERBB2), baseline sTILs, and low tumor cellularity at week 3 predict pCR after ET + double HER2 blockade. Future neoadjuvant trials are needed to prospectively test the use of baseline gene expression and sTILs analysis, and early on-treatment cellularity measurement to select patients with HR+/HER2+ tumors for de-escalated endocrine-therapy-based approaches. Clinical trial information: NCT03272477 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.519
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Platelet-Derived Growth Factor Receptor Beta Serum Concentrations during First-Line Therapy in Ovarian Cancer
    S. Karger AG ; 2013
    In:  Oncology Vol. 85, No. 2 ( 2013), p. 69-77
    Details
    In: Oncology, S. Karger AG, Vol. 85, No. 2 ( 2013), p. 69-77
    Abstract: 〈 b 〉 〈 i 〉 Objectives: 〈 /i 〉 〈 /b 〉 Angiogenesis plays an important role in ovarian cancer. The interaction of platelet-derived growth factor receptor-beta (PDGFR-β) with vascular endothelial growth factor (VEGF) in the process of angiogenesis may represent an essential feature in the progression of the disease. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Patients with epithelial ovarian cancer, who underwent primary surgery and platinum-based first-line chemotherapy, were included. A total of 133 serum samples from 39 patients were analyzed. Samples were prospectively collected at 4 time points: (1) before surgery, (2) after surgery and before chemotherapy, (3) during chemotherapy and (4) after chemotherapy. Serum PDGFR-β was quantified by ELISA. We analyzed the correlation of serum levels to chemotherapy response, progression-free and overall survival (PFS and OS) and the serum markers CA-125 and VEGF-165. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Serum concentration of PDGFR-β ranged between 4 and 72 ng/ml and increased significantly during first-line chemotherapy (p = 0.019). PDGFR-β serum concentrations showed an inverse correlation with CA-125 and VEGF-165 after chemotherapy (r = -0.495, p = 0.003 and r = -0.345, p = 0.04, respectively). Increased PDGFR-β serum levels after chemotherapy were significantly correlated with better PFS (p = 0.026) and OS (p = 0.013) in a univariate analysis. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 PDGFR-β might be a useful biomarker in terms of prognosis and could be important as antiangiogenic agents become a component of standard treatment in ovarian cancer.
    Type of Medium: Online Resource
    ISSN: 0030-2414 , 1423-0232
    URL: Article
    DOI: 10.1159/000351032
    RVK:
    XH 3305
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1483096-6
    detail.hit.zdb_id: 250101-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients
    S. Karger AG ; 2021
    In:  Breast Care Vol. 16, No. 1 ( 2021), p. 50-58
    Details
    In: Breast Care, S. Karger AG, Vol. 16, No. 1 ( 2021), p. 50-58
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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). 〈 b 〉 〈 i 〉 Patients and Methods: 〈 /i 〉 〈 /b 〉 Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis ( 〈 i 〉 n 〈 /i 〉 = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for & #x3e;3 days occurred in & #x3c;15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.
    Type of Medium: Online Resource
    ISSN: 1661-3791 , 1661-3805
    URL: Article
    DOI: 10.1159/000506622
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2205941-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...