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.
In: Clinical cancer research : an official journal of the American Association for Cancer Research, Jg. 29 (2023-02-16), Heft 4, S. 805-814
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Zugriff:
Purpose: To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR- trial (NCT01817452).
Experimental Design: 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 biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline 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.
Results: In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08-2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13-2.61) were favorable, whereas PTEN (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 (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures.
Conclusions: Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR- EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.
(©2022 The Authors; Published by the American Association for Cancer Research.)
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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.
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Autor/in / Beteiligte Person: | Graeser, M ; Gluz, O ; Biehl, C ; Ulbrich-Gebauer, D ; Christgen, M ; Palatty, J ; Kuemmel, S ; Grischke, EM ; Augustin, D ; Braun, M ; Potenberg, J ; Wuerstlein, R ; Krauss, K ; Schumacher, C ; Forstbauer, H ; Reimer, T ; Stefek, A ; Fischer, HH ; Pelz, E ; Zu Eulenburg, C ; Kates, R ; Ni, H ; Kolberg-Liedtke, C ; Feuerhake, F ; Kreipe, HH ; Nitz, U ; Harbeck, N |
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Zeitschrift: | Clinical cancer research : an official journal of the American Association for Cancer Research, Jg. 29 (2023-02-16), Heft 4, S. 805-814 |
Veröffentlichung: | Denville, NJ : The Association, c1995-, 2023 |
Medientyp: | academicJournal |
ISSN: | 1557-3265 (electronic) |
DOI: | 10.1158/1078-0432.CCR-22-1587 |
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