In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.
There was little evidence of weekly cisplatin regimen either for the locally advanced breast cancer or the metastatic setting. We aimed to evaluate that whether the combination of weekly paclitaxel and cisplatin could improve the efficacy of the neoadjuvant treatment for patients with locally advanced breast cancer. Patients with histologically confirmed large operable breast cancer received paclitaxel 80mg/m2 by weekly for 16 weeks and weekly cisplatin 25mg/m2 on day 1, 8 and 15, out of every 28 days for 4-week cycles. Trastuzumab was allowed for HER2-positive disease as weekly continuous regimen. The primary endpoint was locoregional total pathological complete response (tpCR) in breast and axilla lymph nodes after neoadjuvant treatment. One hundred and thirty-one patients were included in the study, among which 34.4% (45/131) patients achieved tpCR. Rate of pathological complete response (pCR) in the breast was 44.3% and the rate of near-pCR in breast was 48.1%. A significantly higher proportion of tpCR was seen in patients with triple negative breast cancer (64.7%, p = 0.003) and HER2 positive (non-luminal) cancer (52.4%, p = 0.018) compared with those who had luminal type tumors (24.7%). At multivariate analysis, negative estrogen receptor and high ki67 level independently predicted a better response. The most frequent toxicities were anemia, leukopenia and peripheral sensory neuropathy. Neoadjuvant chemotherapy by weekly paclitaxel and cisplatin combination was highly effective and tolerated in this study, especially in the triple negative and HER2 positive tumors.
Topoisomerase IIα is not only a proliferation marker of tumor cells, but is also a target for anthracycline-based chemotherapy. Both in vitro and in vivo studies have shown that there is a relationship between topo IIα and chemosensitivity to anthracyclines, but the predictive role of topo IIα in breast cancer patients is still controversial. A meta-analysis based on published studies was performed to obtain an accurate assessment of the association between topo IIα and sensitivity to anthracycline-based chemotherapy. A total of 13 eligible studies, including 2,633 cases and 2,118 controls were identified. Topo IIα was associated with sensitivity to anthracyclines in locally advanced breast cancer patients who received neoadjuvant chemotherapy [five studies, including three using fluorescence in situ hybridization (FISH) and two using immunohistochemistry (IHC): relative risk (RR) = 1.93, 95% confidence interval (95% CI): 1.27-2.94, P = 0.002; two using FISH and three using IHC: RR = 1.98, 95% CI: 1.37-2.86, P < 0.001]. This association existed among three studies using FISH (RR = 2.03, 95% CI: 1.14-3.61, P = 0.017), but did not exist among three studies using IHC (P > 0.05). In early-stage breast cancer patients who received anthracycline-based adjuvant chemotherapy compared with non-taxane-based polychemotherapy, amplification [hazard ratio (HR) = 0.64, 95% CI: 0.49-0.83, P = 0.001; HR = 0.59, 95% CI: 0.35-1.01, P = 0.056] or deletion (HR = 0.82, 95% CI: 0.67-1.00, P = 0.051; HR = 0.58, 95% CI: 0.35-0.97, P = 0.036) of topo IIα was significantly associated with better recurrence-free survival and overall survival. In summary, the present meta-analysis suggests that topo IIα is a predictive factor for breast cancer patients who receive anthracycline-based chemotherapy. Larger and well-designed prospective studies are required to further evaluate the predictive role of topo IIα in clinical practice.
Bladder cancer (BC) is the most popular malignant urinary cancer, with the highest incidence and mortality of all genitourinary system tumors worldwide. To date, the molecular regulation of the metastasis of BC remains ill defined. Here, we examined the levels of matrix metallopeptidase 9 (MMP9) and nuclear β-catenin in the BC specimen. We used lithium chloride (LiCl) to inhibit cytosol β-catenin phosphorylation and degradation to increase nuclear β-catenin levels in BC cells. We used IWP-2 to enhance cytosol β-catenin phosphorylation and degradation to decrease nuclear β-catenin levels in BC cells. We examined MMP9 levels in these experimental settings by quantitative reverse transcription-PCR (RT-qPCR), Western blot, and ELISA. The cell invasiveness was evaluated by Transwell cell assay. We found significantly higher levels of MMP9 and nuclear β-catenin in human BC specimen with metastasis, compared to those without metastasis. Moreover, a strong correlation was detected between MMP9 and nuclear β-catenin. LiCl significantly increased nuclear β-catenin, resulting in MMP9 activation in BC cells. IWP-2 significantly decreased nuclear β-catenin, resulting in MMP9 inhibition in BC cells. MMP9 regulated cell invasiveness. Together, these data suggest that the WNT signaling pathway regulates metastasis of BC through activation of MMP9. Therapies targeting the WNT signaling pathway may be a promising treatment for BC.
In hormone receptor positive breast cancer patients, strong β2 AR expression is correlated with better DFS than weak β2 AR expression and an interaction may exist between β2 AR and hormone receptor pathways. Some limitations of this study were the relatively small sample size and the intrinsic nature of retrospective study per se. Findings of the study are for hypothesis only and need to be confirmed in large prospective studies.
Success in curing breast cancer largely depends on the stage at diagnosis. Circulating microRNAs are becoming a promising noninvasive biomarker. We postulate that a postoperative decline in circulating microRNAs might have diagnostic and prognostic value. Applying high-throughput microarrays, we screened the dysregulated microRNAs in paired serum samples before and after surgery. The relative concentrations of putative markers between the early breast cancer and cancer-free groups were evaluated in the training set and verified in the validation set. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to assess diagnostic value. Survival analysis was performed using Kaplan–Meier estimates and a Cox proportional hazards model. Five microRNAs significantly reduced after surgery were selected for the training set. We found that miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p were significantly higher in the breast cancer group. Each of the four microRNAs had potential diagnostic value. The combined four microRNAs (training set: area under the curve (AUC) 0.8457; validation set: AUC 0.9309) had better diagnostic value than each single microRNA. MiR-222-3p was an independent prognostic factor for disease-free survival (HR = 13.19; 95% CI, 1.06–163.59; P = 0.045). Patients with no fewer than three highly expressed miRNAs had shorter DFS than patients with 0–2 highly expressed miRNAs (HR = 2.293; 95% CI, 1.128–0.662; P = 0.022). Our findings indicate that postoperatively downregulated circulating miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p may be potential biomarkers for breast cancer diagnosis and prognosis.
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