Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 106, Issue 11, Pages -Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/dju291
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Funding
- Breast Cancer Research Foundation (BCRF)
- Spanish Association Against Cancer (Asociacion Espanola Contra el Cancer, AECC)
- AVON Cosmetics
- Fundacion Sandra Ibarra
- Instituto de Salud Carlos III [Intrasalud Intrasalud PI12/02536, PI11/02496]
- Network of Cooperative Cancer Research [RTICC-RD12/0036/0003, RTICC-RD12/0036/0042, RTICC-RD12/0036/0057]
- National Cancer Institute Breast SPORE [P50-CA58223-09A1]
- BCRF
- AECC
- ICREA Funding Source: Custom
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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. p95HER2/611CTF-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 mm(3), 95% confidence interval = 1274 to 538 mm(3); trastuzumab+doxorubicin: 259 mm(3), 95% confidence interval = 387 to 131 mm(3); P < .001). This sensitization may be related to HER2 stabilization induced by chemotherapy in p95HER2/611CTF-positive cells.
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