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PMID: 22370716 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients.

Cancer ·Vol. 118 ·No. 10 ·2012-05-15 ·Pages 2603-14

Jung EJ, Santarpia L, Kim J, Esteva FJ, Moretti E, Buzdar AU, Di Leo A, Le XF, Bast RC, Park ST, Pusztai L, Calin GA

Abstract

Trastuzumab is part of the standard treatment for patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer, but not all patients respond to trastuzumab. Altered microRNA (miR) expression levels in cancer cells have been correlated with prognosis and response to chemotherapy. The authors of this report hypothesized that altered miR expression levels in plasma are associated with sensitivity to trastuzumab in patients with HER-2 positive breast cancer. Quantitative reverse transcriptase-polymerase chain reaction was used to analyze plasma samples, including samples from patients with breast cancer who were enrolled in a clinical trial of neoadjuvant trastuzumab-based chemotherapy. Expression levels of miR-210, miR-21, miR-29a, and miR-126 were analyzed according to the type of response (pathologic complete response [n = 18] vs residual disease [n = 11]). MicroRNA expression levels also were compared in trastuzumab-sensitive and trastuzumab-resistant breast cancer cells derived from BT474 cells and in an independent set of preoperative plasma samples (n = 39) and postoperative plasma samples (n = 30) from 43 breast cancer patients who did not receive any treatment. At baseline before patients received neoadjuvant chemotherapy combined with trastuzumab, circulating miR-210 levels were significantly higher in those who had residual disease than in those who achieved a pathologic complete response (P = .0359). The mean expression ratio for miR-210 was significantly higher in trastuzumab-resistant BT474 cells, and miR-210 expression was significantly higher before surgery than after surgery (P = .0297) and in patients whose cancer metastasized to the lymph nodes (P = .0030). Circulating miR-210 levels were associated with trastuzumab sensitivity, tumor presence, and lymph node metastases. These results suggest that plasma miR-210 may be used to predict and perhaps monitor response to therapies that contain trastuzumab.

MeSH Terms
Adult Aged Antibodies, Monoclonal, Humanized/therapeutic use Antineoplastic Agents/therapeutic use Breast Neoplasms/drug therapy,genetics,pathology Drug Resistance, Neoplasm Female Humans Lymphatic Metastasis MicroRNAs/blood Middle Aged Trastuzumab
Chemicals
Antibodies, Monoclonal, Humanized Antineoplastic Agents MIRN210 microRNA, human MicroRNAs Trastuzumab
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Jung Eun-Jung
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Santarpia Libero
Kim Juyeon
Esteva Francisco J
Moretti Erica
Buzdar Aman U
Di Leo Angelo
Le Xiao-Feng
Bast Robert C
Park Soon-Tae
Pusztai Lajos
Calin George A
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Article Info
Journal
Cancer
Abbr.
Cancer
ISSN
1097-0142
DOI
10.1002/cncr.26565
Published
2012-05-15
Epub
2011-00-05
Pages
2603-14
Language
English
Region
United States
NLM ID
0374236
PMCID
PMC3864019
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA016672 · United States
External Links
PubMed source DOI: 10.1002/cncr.26565 PMC Full Text View journal details
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