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

Eun Jung Jung, Libero Santarpia, Juyeon Kim, Francisco J. Esteva, Erica Moretti, Aman U. Buzdar, Angelo Di Leo, Xiao Feng Le, Robert C. Bast, Soon Tae Park, Lajos Pusztai, George A. Calin

Research output: Contribution to journalArticle

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2011;.

Original languageEnglish
Pages (from-to)2603-2614
Number of pages12
JournalCancer
Volume118
Issue number10
DOIs
Publication statusPublished - May 15 2012

Fingerprint

MicroRNAs
Breast Neoplasms
Neoplasms
Drug Therapy
Trastuzumab
Lymph Nodes
Reverse Transcriptase Polymerase Chain Reaction
Therapeutics
Clinical Trials
Neoplasm Metastasis

Keywords

  • breast cancer
  • microRNA
  • plasma
  • trastuzumab-resistance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jung, E. J., Santarpia, L., Kim, J., Esteva, F. J., Moretti, E., Buzdar, A. U., ... Calin, G. A. (2012). Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer, 118(10), 2603-2614. https://doi.org/10.1002/cncr.26565

Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. / Jung, Eun Jung; 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.

In: Cancer, Vol. 118, No. 10, 15.05.2012, p. 2603-2614.

Research output: Contribution to journalArticle

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 2012, 'Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients', Cancer, vol. 118, no. 10, pp. 2603-2614. https://doi.org/10.1002/cncr.26565
Jung, Eun Jung ; 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. / Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. In: Cancer. 2012 ; Vol. 118, No. 10. pp. 2603-2614.
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abstract = "BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2011;.",
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AU - Jung, Eun Jung

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AU - Kim, Juyeon

AU - Esteva, Francisco J.

AU - Moretti, Erica

AU - Buzdar, Aman U.

AU - Di Leo, Angelo

AU - Le, Xiao Feng

AU - Bast, Robert C.

AU - Park, Soon Tae

AU - Pusztai, Lajos

AU - Calin, George A.

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N2 - BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2011;.

AB - BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Cancer 2011;.

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