Details

Autor(en) / Beteiligte

• Harris, Lyndsay N
• You, Fanglei
• Schnitt, Stuart J
• Witkiewicz, Agnes
• Lu, Xin
• Sgroi, Dennis
• Ryan, Paula D
• Come, Steven E
• Burstein, Harold J
• Lesnikoski, Beth-Ann
• Kamma, Madhavi
• Friedman, Paula N
• Gelman, Rebecca
• Iglehart, J Dirk
• Winer, Eric P

Titel

Predictors of Resistance to Preoperative Trastuzumab and Vinorelbine for HER2-Positive Early Breast Cancer

Ist Teil von

• Clinical cancer research, 2007-02, Vol.13 (4), p.1198-1207

Ort / Verlag

United States: American Association for Cancer Research

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose: To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)–positive breast cancer. Experimental Design: Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. Results: Eight of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T 1 tumors more frequently exhibited clinical complete response ( P = 0.05) and showed a trend to exhibit pCR ( P = 0.07). Five (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR ( n = 3) versus nonresponse ( n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T 4 stage ( P = 0.02) and express basal markers ( P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% versus 97%; P = 0.001). Conclusions: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen.