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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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. / Graeser, Monika; Gluz, Oleg; Biehl, Claudia; Ulbrich-Gebauer, Daniel; Christgen, Matthias; Palatty, Jenci; Kuemmel, Sherko; Grischke, Eva-Maria; Augustin, Doris; Braun, Michael; Potenberg, Jochem; Wuerstlein, Rachel; Krauss, Katja; Schumacher, Claudia; Forstbauer, Helmut; Reimer, Toralf; Stefek, Andrea; Fischer, Hans Holger; Pelz, Enrico; Zu Eulenburg, Christine; Kates, Ronald; Ni, Hua; Kolberg-Liedtke, Cornelia; Feuerhake, Friedrich; Kreipe, Hans Heinrich; Nitz, Ulrike; Harbeck, Nadia; WSG-ADAPT investigators.
In: CLIN CANCER RES, Vol. 29, No. 4, 16.02.2023, p. 805-814.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 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
AU - Graeser, Monika
AU - Gluz, Oleg
AU - Biehl, Claudia
AU - Ulbrich-Gebauer, Daniel
AU - Christgen, Matthias
AU - Palatty, Jenci
AU - Kuemmel, Sherko
AU - Grischke, Eva-Maria
AU - Augustin, Doris
AU - Braun, Michael
AU - Potenberg, Jochem
AU - Wuerstlein, Rachel
AU - Krauss, Katja
AU - Schumacher, Claudia
AU - Forstbauer, Helmut
AU - Reimer, Toralf
AU - Stefek, Andrea
AU - Fischer, Hans Holger
AU - Pelz, Enrico
AU - Zu Eulenburg, Christine
AU - Kates, Ronald
AU - Ni, Hua
AU - Kolberg-Liedtke, Cornelia
AU - Feuerhake, Friedrich
AU - Kreipe, Hans Heinrich
AU - Nitz, Ulrike
AU - Harbeck, Nadia
AU - WSG-ADAPT investigators
PY - 2023/2/16
Y1 - 2023/2/16
N2 - 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.
AB - 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.
U2 - 10.1158/1078-0432.CCR-22-1587
DO - 10.1158/1078-0432.CCR-22-1587
M3 - SCORING: Journal article
C2 - 36441798
VL - 29
SP - 805
EP - 814
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 4
ER -
