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- Title
Effect of p95HER2/611CTF on the Response toTrastuzumab and Chemotherapy.
- Authors
Parra-Palau, Josep Lluís; Morancho, Beatriz; Peg, Vicente; Escorihuela, Marta; Scaltriti, Maurizio; Vicario, Rocio; Zacarias-Fluck, Mariano; Pedersen, Kim; Pandiella, Atanasio; Nuciforo, Paolo; Serra, Violeta; Cortes, Javier; Baselga, José; Perou, Charles M.; Prat, Aleix; Rubio, Isabel T.; Arribas, Joaquín
- Abstract
Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are currently treated with trastuzumab, an anti-HER2 antibody. About 30% of these tumors express a group of HER2 fragments collectively known as p95HER2. Our previous work indicated that p95HER2-positive tumors are resistant to trastuzumab monotherapy. However, recent results showed that tumors expressing the most active of these fragments, p95HER2/611CTF, respond to trastuzumab plus chemotherapy. To clarify this discrepancy, we analyzed the response to chemotherapy of cell lines transfected with p95HER2/611CTF and patient-derived xenografts (n = 7 mice per group) with different levels of the fragment. All statistical tests were two-sided. p95H ER2/611CTF-negative and positive tumors showed different responses to various chemotherapeutic agents, which are particularly effective on p95HER2/611CTF-positive cells. Furthermore, chemotherapy sensitizes p95HER2/611CTF-positive patient-derived xenograft tumors to trastuzumab (mean tumor volume, trastuzumab alone: 906 mm³, 95% confidence interval = 1274 to 538 mm³; trastuzumab+doxorubicin: 259 mm³, 95% confidence interval = 387 to 131 mm³; P < .001). This sensitization may be related to HER2 stabilization induced by chemotherapy in p95HER2/611CTF-positive cells.
- Subjects
TRASTUZUMAB; BREAST cancer chemotherapy; HER2 protein; CELL lines; CANCER chemotherapy; THERAPEUTICS
- Publication
JNCI: Journal of the National Cancer Institute, 2014, Vol 106, Issue 11, p1
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/dju291