Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 504
© 2008 American Society of Clinical Oncology

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Abstract

Biomarkers as potential predictors of pathologic complete response (pCR) in the NOAH trial of neoadjuvant trastuzumab in patients (pts) with HER2-positive locally advanced breast cancer (LABC)

Istituto Nazionale Tumori Milano, Milan, Italy; Frauenklinik Vom Roten Kreuz, Munich, Germany; University of Texas M. D. Anderson Cancer Center, Houston, TX; NN Petrov Research Institute of Oncology, St. Petersburg, Russian Federation; Roche Diagnostics GmbH, Penzberg, Germany; City Oncology Hospital; Monogram Biosciences Inc, South San Francisco, CA; Fondazione Michelangelo, Milan, Italy; Vall d'Hebron University Hospital, Barcelona, Spain

504

Background: The NOAH trial evaluated the addition of trastuzumab (H) to chemotherapy (CT) for pts with HER2-positive LABC. A significant improvement in pCR has been reported (Gianni. ASCO 2007; abs 532). Methods: 228 pts were randomized to receive 3 cycles of doxorubicin (60 mg/m²) and paclitaxel (150 mg/m²) q3w, 4 cycles of paclitaxel (175 mg/m² q3w) and 3 cycles of CMF (C 600 mg/m², M 40 mg/m², F 600 mg/m² d 1+8 q4w) with or without concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. 171 (75%) core biopsies obtained before treatment were available for assays of c-Myc (by FISH), PTEN (by IHC) and IGF1R (by IHC) in addition to estrogen receptor (ER) and progesterone receptor (PgR). Results: The 171 pts with available biopsies were representative of the overall NOAH population, although with a lower incidence of ER+ tumors. Negative PgR status was strongly associated with pCR in the H group (51% vs 16% in PgR-positive tumors; p=0.008). Overall, 32 pts had c-Myc amplification (cut-off ratio >2). Of these, 11/21 (52%) H pts but only 1/11 (9%) CT pts had pCR. PTEN expression was not predictive of pCR after H but was associated with a higher pCR rate after CT alone (p=0.05). IGF1R membrane staining was significantly lower in H-treated pts with pCR than those with residual disease (24% vs 48%; p=0.05). In logistical regression analysis, PgR status and H treatment were significant predictors of pCR. In the H-treated group, PgR status (p=0.012) was the most significant predictor of pCR; ER and IGF1R membrane staining showed borderline significance (p=0.089 and p=0.075, respectively). Conclusions: PgR-negative status and c- Myc amplification are associated with higher pCR rates after addition of H compared to CT alone. Overexpression of membranous IGF1R is associated with a higher likelihood of residual disease after H-based CT. These results will be combined with those of ongoing studies of additional biomarkers (HER3, p95HER2 and HER2 homodimers) to define a multivariate residual disease predictor.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GenentechTM BioOncology, Roche MGRM GenentechTM BioOncology, Roche Roche

Abstract presentation from the 2008 ASCO Annual Meeting