BACKGROUND
Trastuzumab is part of the standard treatment for HER-2 positive breast cancer patients, but not all patients respond to trastuzumab. Altered expression levels for microRNAs in cancer cells have been correlated with prognosis and response to chemotherapy. We hypothesized that altered expression levels for miRNAs in plasma are associated with sensitivity to trastuzumab in patients with HER-2 positive breast cancer.
METHODS
We performed quantitative RT-PCR in plasma samples including breast cancer patients enrolled in a clinical trial of neoadjuvant trastuzumab-based chemotherapy. We analyzed expression levels for miR-210, -21, -29a, and -126 according to the type of response (pCR (n = 18) vs. residual disease (n = 11)). We also compared expression levels of miRNAs in trastuzumab-sensitive and –resistant breast cancer cells derived from BT474 cells and in an independent set of preoperative (n=39) and postoperative plasma (n=30) from 43 breast cancer patients not given any treatment.
RESULTS
At baseline before neoadjuvant chemotherapy combined with trastuzumab, circulating miR-210 levels were significantly higher in patients who had residual disease than in those who had pathologic CR (P = 0.0359). 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 = 0.0297) and in patients whose cancer metastasized to the lymph nodes (P = 0.0030).
CONCLUSIONS
Circulating miR-210 levels were associated with trastuzumab sensitivity, tumor presence, and lymph node metastases. This suggests that plasma miR-210 may be used to predict and perhaps monitor response to therapies containing trastuzumab.
Patients with a high preoperative TSH level and small thyroid volume are at high risk of developing hypothyroidism following hemithyroidectomy. Potential risk of postoperative hypothyroidism should be discussed with these patients when thyroid surgery is being considered for a diagnostic purpose.
The use of ultrasonography (USG) has become an essential part of endocrine surgical practice. We evaluated the value of USG in predicting malignancy of thyroid nodules. The accuracy of USG in 857 patients who underwent fine-needle aspiration (FNA) with or without surgery was analyzed in a prospective setting. The diagnostic accuracy of USG was compared to that of FNA and of combined models in 153 operated patients. The malignancy-predicting value of USG in follicular neoplasms and its relation to nodule size were also investigated. Sensitivity, specificity, and overall accuracy (OA) of USG were 84.9%, 95.5%, and 93.7%, respectively. In operated patients, USG had accuracy comparable to that of FNA and combined models (sensitivity 93.3%, specificity 90.6%, OA 92.0%) regardless of nodule size but showed a significant rate of indeterminate results (29.4%). For follicular neoplasms, the sensitivity, specificity, and OA of USG were 100%, 95.4%, and 96.1%, respectively, with indeterminate results for three malignant nodules (42.8%). This acceptable malignancy-predicting value of USG in thyroid nodules supports the potential role of USG for predicting malignancy in selected patients with thyroid nodules. However, the high rate of indeterminate results precludes it from being a standard independent diagnostic method for the present time.
Endoscopic thyroidectomy using a gasless axillary approach is a safe procedure that offers a good cosmetic result and has the merits of minimal invasiveness even in patients with a large thyroid mass. It is a safe and feasible alternative to traditional thyroid surgery, especially in young female patients with a large thyroid mass.
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