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Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial

Overview of attention for article published in Clinical Cancer Research, December 2022
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (85th percentile)
  • Good Attention Score compared to outputs of the same age and source (65th percentile)

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Title
Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial
Published in
Clinical Cancer Research, December 2022
DOI 10.1158/1078-0432.ccr-22-1587
Pubmed ID
Authors

Monika Graeser, Oleg Gluz, Claudia Biehl, Daniel Ulbrich-Gebauer, Matthias Christgen, Jenci Palatty, Sherko Kuemmel, Eva-Maria Grischke, Doris Augustin, Michael Braun, Jochem Potenberg, Rachel Wuerstlein, Katja Krauss, Claudia Schumacher, Helmut Forstbauer, Toralf Reimer, Andrea Stefek, Hans Holger Fischer, Enrico Pelz, Christine zu Eulenburg, Ronald Kates, Hua Ni, Cornelia Kolberg-Liedtke, Friedrich Feuerhake, Hans Heinrich Kreipe, Ulrike Nitz, Nadia Harbeck

Abstract

TTo identify associations of biological signatures and stromal tumor infiltrating lymphocytes (sTILs) with pathological complete response (pCR, ypT0 ypN0) and survival in the phase II WSG-ADAPT HER2+/HR- trial (NCT01817452). Patients with cT1-cT4c, cN0-3 HER2+/HR- early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n=92) or P+T+paclitaxel (n=42). Gene expression signatures were analyzed in baseline (BL) biopsies using NanoString Breast Cancer 360 panel (n=117); BL and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression. In all patients, ERBB2 (OR 1.70; 95%CI 1.08-2.67) and estrogen receptor (ER) pathway signaling signatures (OR 1.72; 95%CI 1.13-2.61) were favorable, while PTENsignature (OR 0.57; 95%CI 0.38-0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n=11, P+T+paclitaxel: n=2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43-0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR 2.00; 95%CI 1.04-3.84). IR signatures were strongly intercorrelated. sTILs (BL/week 3/change) were not associated with pCR or iDFS, though BL-sTILs correlated positively with IR signatures. Distinct gene signatures were associated with pCR vs iDFS in HER2+/HR- EBC. The potential role of IR in preventing recurrence suggests that patients with up-regulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.

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Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 November 2022.
All research outputs
#3,622,125
of 22,780,967 outputs
Outputs from Clinical Cancer Research
#3,400
of 12,586 outputs
Outputs of similar age
#33,329
of 233,900 outputs
Outputs of similar age from Clinical Cancer Research
#29
of 83 outputs
Altmetric has tracked 22,780,967 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,586 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.8. This one has gotten more attention than average, scoring higher than 72% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 233,900 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 85% of its contemporaries.
We're also able to compare this research output to 83 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.