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  • American Association for Cancer Research (AACR)  (4)
  • 1
    Online Resource
    Online Resource
    Abstract GS4-03: Neoadjuvant nab-paclitaxel weekly versus dose-dense paclitaxel followed by dose-dense EC in high risk HR+/HER2- early BC by: Results from the neoadjuvant part of ADAPT HR+/HER2- trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-03-GS4-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-03-GS4-03
    Abstract: 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 predictive for pCR. Still, no prospective data are available so far to predict chemotherapy efficacy in this key patient group. Use of dose-dense chemotherapy is associated with improved outcome in meta-analysis, but its use in the neoadjuvant setting is less studied. Furthermore, use of nab-paclitaxel instead of solvent-based paclitaxel has shown promising results in some studies. Here, we present for the first time data from a randomized prospective trial comparing these risk-selection strategies according to RS and Ki67 decrease in high-risk HR+/HER2- BC. Methods: High-risk BC patients [cN0-1 with RS & gt;25 or (RS 12-25 AND (centrally measured) post-endocrine Ki67 & gt;10%] OR [cN2-3 status] OR [G3 AND Ki67 & gt;40%] were randomized to (neo)adjuvant 4x paclitaxel175 q2w or 8xnab-paclitaxel 125 mg/m2q1w followed by 4x E90C600 q2w. pCR was defined as no invasive tumor in breast and lymph nodes. Results: 858 patients with available surgery data randomized to neoadjuvant Pac-EC (N=423) or nab-Pac-EC (N=435) were analyzed. Median age was 51 years; median RS was 30 (N=572); 34% had node-positive; 46% (locally) G3 tumors. Baseline characteristics were well balanced between study arms. Patients receiving nab-Pac-EC had higher pCR than those with Pac-EC (20.3% vs. 12.3%, p=.002); patients with RS & lt;25 (about 27%) had a lower pCR rate than those with RS & gt;25 (6.5% vs. 15.8%, p=.003). The association of RS with pCR appeared more pronounced in premenopausal women, but a test of interaction was not significant; RS was about 3 points higher (mean 32.9 vs. 29.8, p & lt;.001) in postmenopausal cases (p=.001). Clinical tumor stage cT2-4 was reported in 65%, with a lower pCR rate than in cT1 tumors (14% vs. 20%, p=.02). RS was moderately correlated (R=.45) with baseline Ki67. In multivariable analysis with tumor stage, RS, Ki67, menopausal status, and ER and PR positivity, higher RS and cT1 stage were favorable for pCR. Excluding RS, higher Ki67 and lower ER (as well as cT1) were favorable. In patients with RS & lt;25, there was no pCR with Pac-EC (0/72 pCR); pCR was almost 20% with RS & gt;25 and nab-Pac-EC. Further details and data including impacts of Ki67 dynamics and additional markers on pCR will be presented at the meeting. Conclusions: Use of neoadjuvant nab-paclitaxel instead of solvent-based paclitaxel appears promising within a short (16-weeks) dose-dense chemotherapy schedule in high-risk HR+/HER2- BC. For the first time, data from a large neoadjuvant randomized trial confirm RS could help to select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- breast cancer (BC). Citation Format: Sherko Kuemmel, Oleg Gluz, Ulrike Nitz, Michael Braun, Matthias Christgen, Kerstin Luedtke-Heckenkamp, Raquel von Schumann, Maren Darsow, Helmut Forstbauer, Jochem Potenberg, Eva-Maria Grischke, Bahriye Aktas, Claudia Schumacher, Ronald Kates, Monika Graeser, Rachel Wuerstlein, Christoph Uleer, Michael Hauptmann, Steve Shak, Rick Baehner, Hans Kreipe, Nadia Harbeck, West German Study Group. Neoadjuvant nab-paclitaxel weekly versus dose-dense paclitaxel followed by dose-dense EC in high risk HR+/HER2- early BC by: Results from the neoadjuvant part of ADAPT HR+/HER2- trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-GS4-03
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma
    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 6 ( 2019-03-15), p. 1113-1123
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 6 ( 2019-03-15), p. 1113-1123
    Abstract: Identifying controlling features of responsiveness to checkpoint blockade therapies is an urgent goal in oncology research. Our group and others have previously shown melanoma tumors resistant to checkpoint blockade display features of mesenchymal transition, including E-cadherin loss. Here, we present the first in vivo evidence that E-cadherin from tumor cells facilitate immune attack, using a B16F10 melanoma mouse model in which E-cadherin is exogenously expressed (B16.Ecad). We find, compared with vector control, B16.Ecad exhibits delayed tumor growth, reduced metastatic potential, and increased overall survival in vivo. Transplantation of B16.Ecad into Rag1−/− and CD103−/− mice abrogated the tumor growth delay. This indicates the anti-melanoma response against B16.Ecad is both immune and CD103+ mediated. Moreover, B16.Ecad showed increased responsiveness to combination immune checkpoint blockade (ICB) compared with vector control. This work establishes a rationale for ICB responses observed in high E-cadherin–expressing tumors and suggests therapeutic advancement through amplifying CD103+ immune cell subsets. Significance: These findings identify the mechanism behind checkpoint blockade resistance observed in melanoma that has undergone mesenchymal transition and suggest activation of CD103+ immune cells as a therapeutic strategy against other E-cadherin–expressing malignancies.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-18-1722
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    The Association between Polluted Neighborhoods and TP53 -Mutated Non–Small Cell Lung Cancer
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 30, No. 8 ( 2021-08-01), p. 1498-1505
    Details
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 30, No. 8 ( 2021-08-01), p. 1498-1505
    Abstract: Poor patients often reside in neighborhoods of lower socioeconomic status (SES) with high levels of airborne pollutants. They also have higher mortality from non–small cell lung cancer (NSCLC) than those living in wealthier communities. We investigated whether living in polluted neighborhoods is associated with somatic mutations linked with lower survival rates, i.e., TP53 mutations. Methods: In a retrospective cohort of 478 patients with NSCLC treated at a comprehensive cancer center between 2015 and 2018, we used logistic regression to assess associations between individual demographic and clinical characteristics, including somatic TP53 mutation status and environmental risk factors of annual average particulate matter (PM2.5) levels, and neighborhood SES. Results: 277 patients (58%) had somatic TP53 mutations. Of those, 45% lived in neighborhoods with “moderate” Environmental Protection Agency–defined PM2.5 exposure, compared with 39% of patients without TP53 mutations. We found significant associations between living in neighborhoods with “moderate” versus “good” PM2.5 concentrations and minority population percentage [OR, 1.06; 95% confidence interval (CI), 1.04–1.08]. There was a significant association between presence of TP53 mutations and PM2.5 exposure (moderate versus good: OR, 1.66; 95% CI, 1.02–2.72) after adjusting for patient characteristics, other environmental factors, and neighborhood-level SES. Conclusions: When controlling for individual- and neighborhood-level confounders, we find that the odds of having a TP53-mutated NSCLC are increased in areas with higher PM2.5 exposure. Impact: The link between pollution and aggressive biology may contribute to the increased burden of adverse NSCLC outcomes in individuals living in lower SES neighborhoods.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    URL: Article
    DOI: 10.1158/1055-9965.EPI-20-1555
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 4
    Online Resource
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    Abstract GS4-04: Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score 〈26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-04-GS4-04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-04-GS4-04
    Abstract: Background: In HR+/HER2- N0 early breast cancer (EBC), patients (pts) with Recurrence Score™ (RS) & lt;26 (postmenopausal) and & lt;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 context of genomic signatures remainunclear. For the first time, we present survival results from the large prospective phase III WSG-ADAPTHR+/HER- trial combining both static (RS in baseline core biopsy) and dynamic (Ki67 response)biomarkers to optimize adjuvant therapy in luminal EBC. Methods: 5625 pts were registered and 4691 finally treated by ET (n=2356) or CT (n=2335) within ADAPTHR+/HER2-. ET-trial ITT population comprised 2290 pts: n=868 RS0-11, n=1422 RS12-25/ET-response(30% premenopausal, 26% N1). 5y-iDFS was 93.9% (95%-CI: [91.8% to 95.4%]) in RS0-11 and 92.6%(95%-CI: [90.8% to 94.0%] ) in RS12-25/ET-responders. Since the one-sided upper 95% confidence limitof the 5y-iDFS difference was 3.3%, the pre-specified criterion to accept the primary NI-hypothesis wasmet (p=.05).5y-dDFS was 96.3% [94.6% to 97.5%] vs. 95.6% [94.2% to 96.7%] ) in RS0-11 vs. RS12-25/ET-responders,respectively (95%-CI for 5y-dDFS difference: [-1.2% to 2.6%]). 5y-OS was also excellent and similar(98.0% [96.7% to 98.9%] vs. 97.3% [96.1 to 98.1%]) in RS0-11 vs. RS12-25/ET-responders, respectively(95% CI for the 5y-OS difference: [-0.7% to 2.2%] ). Results: 5625 pts were registered and 4691 finally treated by ET (n=2356) or CT (n=2335) within ADAPTHR+/HER2-. ET-trial ITT population comprised 2290 pts: n=868 RS0-11, n=1422 RS12-25/ET-response(30% premenopausal, 26% N1). 5y-iDFS was 93.9% (95%-CI: [91.8% to 95.4%]) in RS0-11 and 92.6%(95%-CI: [90.8% to 94.0%] ) in RS12-25/ET-responders. Since the one-sided upper 95% confidence limit of the 5y-iDFS difference was 3.3%, the pre-specified criterion to accept the primary NI-hypothesis was met (p=.05) 5y-dDFS was 96.3% [94.6% to 97.5%] vs. 95.6% [94.2% to 96.7%] ) in RS0-11 vs. RS12-25/ET-responders, respectively (95%-CI for 5y-dDFS difference: [-1.2% to 2.6%]). 5y-OS was also excellent and similar (98.0% [96.7% to 98.9%] vs. 97.3% [96.1 to 98.1%]) in RS0-11 vs. RS12-25/ET-responders, respectively (95% CI for the 5y-OS difference: [-0.7% to 2.2%] ). Conclusions: In pN0-1 luminal EBC pts receiving ET alone, pts with RS12-25/ET-response had 5y-iDFSwell above 90% and very close to RS0-11 pts. Both groups had excellent similar dDFS and OS. DynamicET response thus complements RS as a key selection criterion for omission of chemotherapy in pN0-1HR+/HER2- EBC. Citation Format: Nadia Harbeck, Oleg Gluz, Sherko Kuemmel, Matthias Christgen, Michael Braun, Bahriye Aktas, Kerstin Luedtke-Heckenkamp, Helmut Forstbauer, Eva-Maria Grischke, Claudia Schumacher, Maren Darsow, Katja Krauss, Benno Nuding, Marc Thill, Jochem Potenberg, Christoph Uleer, Mathias Warm, Hans H. Fischer, Wolfram Malter, Michael Hauptmann, Ronald Kates, Monika Graeser, Rachel Wuerstlein, Steve Shak, Rick Baehner, Hans Kreipe, Ulrike Nitz, West German Study Group. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score & lt;26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-GS4-04
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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