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Keywords:

  • microRNA;
  • plasma;
  • breast cancer;
  • trastuzumab-resistance

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;. © 2011 American Cancer Society.