Validation of the Eighth American Joint Committee on Cancer Anatomic and Prognostic Staging System for Breast Cancer.

BACKGROUND: The eighth edition of new staging systems for breast cancer incorporated four biological factors and the anatomic staging system. Validating analysis on Chinese patients has been limited. Our study performed analysis comparing the prognostic value of the staging system based on Chinese data. METHODS AND MATERIALS: All patients were classified according to the eighth edition and compared between anatomic and prognostic staging systems. The Kaplan-Meier test was used to calculate the overall survival (OS) and disease-free survival (DFS). We performed Harrell concordance index (C-index) analyses to quantify a models' predictive performance. Akaike information criterion (AIC) via Cox regression analysis was used to conduct bootstrap-based goodness-of-fit comparisons of the competing staging systems. RESULTS: A total of 1556 patients were enrolled in the cohort. The median follow-up time was 76 mo (range, 4-146 mo), the median age was 48 y old (range, 21-87 y). The ratio of movement between anatomic stage (AS) and prognostic stage (PS) was 50.9%. Of these, 691 (44.5%) AS patients were down staged and 100 (6.4%) patients were upstaged when reclassified based on PS. Significant differences between two stages were achieved for stage IIIC in 5-y OS rates and for IIIB in 5-y DFS rates (63.5% versus 50.0% and 58.0% versus44.0%). The value of the C-index for PS and AS were 0.711 and 0.687 (P = 0.04). The AIC reaches a value of 3452.9 for the PS and a value of 3476.4 for the AS. CONCLUSIONS: The PS might provide better accuracy than the AS in predicting the prognosis of Chinese female breast cancer patients. It also provides a strong basis for the utility of clinical biomarkers to evaluate the prognosis of patients.

Survival and time to initiation of adjuvant chemotherapy among breast cancer patients: a systematic review and meta-analysis.

The relationship between survival and time to the start of adjuvant chemotherapy (AC) among breast cancer patients is unclear. In order to illustrate the effect of delaying the initiation of AC on survival we have undertaken a systematic review and meta-analysis. We identified 12 available studies in the meta-analysis including 15 independent analytical groups. This meta-analysis showed that a 4-week delay before AC was associated with a significantly worse overall survival (OS)(HR=1.13; 95% confidence interval [CI], 1.08-1.19) and disease free survival (DFS)(HR=1.14; 95%CI, 1.05-1.24). Two studies categorized patients into hormone receptor-positive, ERBB2-positive, and triple-negative breast cancer (TNBC) patients according to the clinicopathological features of breast cancer. The HRs for OS between waiting time (WT) ≤30 days and 31-60 days in the subgroups were extracted and analyzed. The analysis demonstrated that a WT of 31-60 days was related to worse OS among patients with TNBC (HR, 1.26; 95% CI, 1.08-1.48), but had no significant effect on OS among those with hormone receptor-positive (HR, 1.02; 95% CI, 0.89-1.15) or ERBB2-postive (HR, 0.95; 95%CI, 0.79-1.14) tumors. In this meta-analysis of the eligible literatures reviewing the time to AC, a longer waiting time to adjuvant chemotherapy may lead to worse survival in breast cancer patients, especially in TNBC patients.

[Correlation of miR-195 with invasiveness and prognosis of breast cancer].

OBJECTIVE: To explore the potential role of miR-195 on invasiveness and prognosis of breast cancer. METHODS: The RNA in formalin-fixed paraffin embedded (FFPE) of 88 breast cancer patients with primary tumors was extracted, and miR-195 levels were quantified by quantitative real-time polymerase chain reaction (real-time PCR). The relationship of miR-195 levels and clinicopathological variables were assessed by Mann Whitney-U test. Recurrence-free survival and overall survival curves were derived from Kaplan-Meier estimates and the curves were compared by Log-rank tests. Cox regression analysis was used for multivariate analysis. All statistical tests were two-sided. RESULTS: The levels of miR-195 in the breast cancer with histological high grade, tumor size of T3-4, lymph nodal involvement or vessel invasion were significantly down-regulated, compared with those of patients with histological low grade (Z = -2.271, P = 0.023), tumor size of T1-2 (Z = -2.687, P = 0.007), no lymph node metastasis (Z = -1.967, P = 0.049) and vessel invasion (Z = -2.432, P = 0.015). In addition, no statistically significant difference (P > 0.05) was identified between miR-195 levels and hormone receptors status, HER-2 expression, TNM stage, tumor types, recurrence and menstrual status. When considering 2(-ΔCt) = 0.270 (median level) as cut-off value, Kaplan-Meier survival analysis indicated that patients with high miR-195 level showed a positive association towards a longer survival, either recurrence-free survival (χ(2) = 5.985, P = 0.014) or overall survival (χ(2) = 30.05, P = 0.000). In a multivariate analysis, miR-195 expression on FFPE correlated significantly with outcomes of breast cancer (HR = 0.040, 95%CI: 0.009 - 0.179, P = 0.000) and was independent of other prognostic factors. CONCLUSIONS: It suggests that miR-195 expression on FFPE is inversely correlated with histological high grade, bigger tumor size, lymph node involvement, vessel invasion. Furthermore, as independent prognostic factor, low miR-195 significantly contributes to poor outcomes of breast cancer.

[Correlation of polymorphism rs1563828 in MDM4 gene with breast cancer risk and onset age].

OBJECTIVE: To explore effect of polymorphism rs1563828 (C > T) in human murine double minute 4 gene (MDM4) on genetic susceptibility for early-onset breast cancer and potential association with age of onset of breast cancer. METHODS: One hundred and twenty-four early-onset breast cancer patients (age ≤ 35 years at time of diagnosis) from independent families admitted from January 2006 to June 2010 and 101 age-matched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction and then MALDI-TOF-MS assay. Association of genotype distribution and breast cancer risk was evaluated by χ(2) test. The odd-ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional Logistic regression model. The t test was used to compare the age and demographic differences among groups. RESULTS: The frequency of rs1563828 polymorphism genotypes in control group were CC 43.6% (44/101), CT 42.6% (43/101), TT 13.9% (14/101), and in case group were 42.7% (53/124), 46.0% (57/124), 11.3% (14/124), respectively. No significant difference (χ(2) = 0.449, P = 0.799) was reached by χ(2) test. rs1563828CT or TT genotype does not confer a significantly increased risk for breast cancer compared with CC genotype after adjusting for age, menarche in Logistic regression analysis (OR = 1.024, 95%CI: 0.581 - 1.806, P = 0.934). TT carriers were observed to develop breast cancer earlier than CC/CT carriers [(30 ± 4) years vs. (32 ± 3) years, P = 0.028]. CONCLUSIONS: The rs1563828(C > T) polymorphism in MDM4 gene may not confer risk to breast cancer, especially for early-onset breast cancer patients. Homozygous TT of rs1563828 is associated with younger age to develop breast cancer.

[Correlation of miR-155 on formalin-fixed paraffin embedded tissues with invasiveness and prognosis of breast cancer].

OBJECTIVE: To investigate the potential use of miR-155 as novel breast cancer biomarker. METHODS: There were 88 breast cancer patients underwent modified mastectomy and had detailed clinical follow-up information. Extracting RNA from the formalin-fixed paraffin embedded (FFPE) samples, miR-155 levels were quantified by real-time-PCR. miR-155 levels among clinico-pathological variables were accessed by Mann Whitney-U test. Overall survival curve was derived from Kaplan-Meier estimates and the curve was compared by Log-rank test. Cox regression analysis was used for multivariate analysis. All statistical tests were two-sided. RESULTS: Significantly higher miR-155 level was found in tumor tissue compared to paired normal tissue (t = 6.75, P = 0.000). A potential relationship between miR-155 levels and existing clinico-pathological parameters of breast cancer, such as menstrual status, tumor size, nodal involvement, stage of disease, hormone receptor status, HER-2 status, histological grade or tumor subtype was investigated. Up-regulated miR-155 level was observed in breast cancer with lymph node metastasis, pT3+4, advanced TNM stage, HER-2 positive and with vascular invasion (Z = -6.320 to -2.041, P = 0.000 to 0.041). When considering 2(-ΔCt) = 4.87 (median level) as cut-off value, patients with miR-155 up-regulation showed a positive association towards a shorter overall survival (χ(2) = 6.396, P = 0.011). In Cox multivariate analysis, miR-155 expression on FFPE was shown an inverse trend for outcomes of breast cancer (HR = 1.58, 95%CI: 0.87 - 3.16, P = 0.082). CONCLUSIONS: miR-155, as an oncomir, promotes lymph node involvement and vascular invasion and accompanies over-expressed HER-2 on breast cancer FFPE tissue. It suggests that miR-155 could predict the invasiveness.