Low expression of stathmin in tumor predicts high response to neoadjuvant chemotherapy with docetaxel-containing regimens in locally advanced breast cancer.

AIMS: We performed this retrospective study to evaluate the value of clinicopathological factors and a novel molecular marker stathmin in predicting treatment response to neoadjuvant chemotherapy (NCT) with docetaxel-containing regimens in patients with locally advanced breast cancer. METHODS: Fifty-four consecutive locally advanced patients receiving docetaxel-containing NCT between January 2006 and July 2010 in Zhejiang Cancer Hospital were included. The expression levels of estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor-2 (HER-2), and p53 were detected by immunohistochemistry, while expression of stathmin mRNA was measured by Quanti-Gene assay. RESULTS: The overall clinical objective response (cOR) rate was 75.9% (41/54) in breast. A total of 34 patients (63.0%) experienced pathological OR (pOR), with pathological complete remission (pCR) rate of 20.4% (11/54) in breast and 16.7% (9/54) in both breast and axilla. In univariate analysis, there were associations of pOR in both breast and axilla with age (p=0.054), ER status (p=0.059), subtypes (p=0.062), p53 (p=0.030), and stathmin expression (three terciles) (p=0.039). Mean expression of stathmin in pOR group was 0.410, compared with that in no response group of 0.556 (p=0.051 by Student's t-test). Similarly, a lower expression of stathmin might represent a higher pCR rate (p=0.061). Moreover, the LOWESS smoothing plot showed the same trend, that is, that tumor with a lower level of stathmin expression had a higher probability of response to docetaxel-containing NCT. After multivariate adjustment, both ER and stathmin remained significant with hazard ratio of 4.58 (95% CI: 1.11-18.94, p=0.036) and 2.94 (95% CI: 1.26-6.86, p=0.012), respectively. CONCLUSIONS: In conclusion, ER and stathmin were independent predictive factors for NCT with docetaxel-containing regimens.

Primary study of lymph node metastasis-related serum biomarkers in breast cancer.

The aim of this study was to detect the pretreatment serum protein profiles of breast cancer patients by mass spectrometry (MS) to screen candidate tumor biomarkers, which will supply a simple, accurate, and minimally invasive method to predict the axillary lymph node metastasis of breast cancer. We used magnetic bead-based weak cation-exchange chromatography followed by matrix-assisted laser desorption and ionization time-of-flight MS to detect proteins in the sera of 54 cases of axillary node-negative breast cancer, 47 cases of axillary node-positive breast cancer, and 101 healthy controls. The protein profiles were analyzed to screen tumor biomarkers and lymph node metastasis-associated proteins to establish and verify a diagnostic model. Comparison of the protein profiles between the two cancer groups resulted in a total of 111 discriminate m/z peaks that were associated with breast cancer. Furthermore, 40 discriminate m/z peaks were detected between breast cancer patients with and without axillary node metastases. Four protein m/z peaks at 5,643, 4,651, 2,377, and 2,240 were used to construct a diagnosis model, and cross-validation indicated that breast cancer with and without axillary node metastasis was identified with 87.04% sensitivity (47/54), 87.23% specificity (41/47), and 87.13% accuracy (88/101). These proteins could potentially be used as predictive biomarkers to distinguish between breast cancer patients with or without lymph node metastasis.

Unilateral hemilaminectomy for patients with intradural extramedullary tumors.

A modified hemilaminectomy was introduced in an attempt to explore the operative techniques and the values of the limited approach to spinal cord tumors. Forty-five consecutive patients with intradural extramedullary lesions, who underwent modified hemilaminectomy, were studied retrospectively. The intraspinal tumors were removed via the limited bone window with a 3.3-cm mean length (range: 2.0-6.5 cm) and a 1.2-cm mean width (range: 0.6-1.5 cm), in which the inner parts of the medial and lateral laminae were mostly undercut for wider view. Spinal lesions were cervical in 21 cases, thoracic in 12 cases, lumbar in 10 cases, and multiple in 2 cases. Forty-three cases were completely excised via hemilaminectomy alone. Two subjects with dumbbell neurinoma underwent two-stage tumor removal via anterolateral cervical approach following hemilaminectomy. With respect to neurological status, the percentage of good Frankel scale (D+E grade) was markedly improved from 22.2% on admission to 93.3% at follow-up. At the median 26-month follow-up evaluation by magnetic resonance imaging (MRI), none of the subjects showed spinal deformity or instability. By preserving musculoligamentous attachments and posterior bony elements as much as possible, the modified approach is minimally invasive and may be routinely used to remove intradural and extramedullary tumors, especially in patients with meningiomas and neurinomas.

Recursive partitioning analysis classification and graded prognostic assessment for non-small cell lung cancer patients with brain metastasis: a retrospective cohort study.

OBJECTIVE: To assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). METHODS: From Jan 2008 to Dec 2009, the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation, systemic chemotherapy and tyrosine kinase inhibitors (TKIs) in two institutes were analyzed. Survival was estimated by Kaplan-Meier method. The differences of survival rates in subgroups were assayed using log-rank test. Multivariate Cox's regression method was used to analyze the impact of prognostic factors on survival. Two prognostic indexes models (RPA and GPA) were validated respectively. RESULTS: All patients were followed up for 1-44 months, the median survival time after brain irradiation and its corresponding 95% confidence interval (95% CI) was 14 (12.3-15.8) months. 1-, 2- and 3-year survival rates in the whole group were 56.0%, 28.3%, and 12.0%, respectively. The survival curves of subgroups, stratified by both RPA and GPA, were significantly different (P<0.001). In the multivariate analysis as RPA and GPA entered Cox's regression model, Karnofsky performance status (KPS) ≥ 70, adenocarcinoma subtype, longer administration of TKIs remained their prognostic significance, RPA classes and GPA also appeared in the prognostic model. CONCLUSION: KPS ≥70, adenocarcinoma subtype, longer treatment of molecular targeted drug, and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.