Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial.

BACKGROUND: Recently, the use of taxane-based regimens before anthracycline-based regimens has been shown to achieve high pathological complete response (pCR) rates in patients with breast cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) has been reported as highly effective and less toxic compared with Cremophor-based Taxol. This phase II clinical trial evaluated the safety and efficacy of preoperative neoadjuvant chemotherapy (NAC) with nab-PTX followed by an epirubicin plus cyclophosphamide (EC)-based regimen for operable breast cancer. PATIENTS AND METHODS: From June 2012 to January 2014, four cycles of every-3-week (q3w) nab-PTX [plus q3w trastuzumab in cases of human epidermal growth factor 2 (HER2) positivity] followed by four cycles of q3w EC were administered to patients with operable breast cancer (stage IC-IIIA). The primary endpoint was the pCR rate (ypT0/TisypN0). RESULTS: A total of 55 patients were enrolled, 54 of whom received at least one nab-PTX dose. All patients underwent radical surgery after chemotherapy. The overall pCR rate was 22.2% (p = 0.006). The pCR rates for patients with the luminal B, luminal/HER2, HER2-rich, and triple-negative breast cancer subtypes were 10.5, 29.4, 60, and 15.4%, respectively. Stepwise logistic regression analysis revealed only HER2 as a significant factor for pCR (odds ratio 5.603; p = 0.024). The expression of secreted protein acidic and rich in cysteine showed no association with pCR. The clinical response rate was 70.4% (38/54), and the safety profile was tolerable. CONCLUSION: Preoperative NAC with nab-PTX followed by EC is effective and safe for operable breast cancer.

Prediction of macrometastasis in axillary lymph nodes of patients with invasive breast cancer and the utility of the SUV lymph node/tumor ratio using FDG-PET/CT.

BACKGROUND: Axillary lymph node dissection (ALND) is important for improving the prognosis of patients with node-positive breast cancer. However, ALND can be avoided in select micrometastatic cases, preventing complications such as lymphedema or paresthesia of the upper limb. To appropriately omit ALND from treatment, evaluation of the axillary tumor burden is critical. The present study evaluated a method for preoperative quantification of axillary lymph node metastasis using positron emission tomography/computed tomography (PET/CT). METHODS: The records of breast cancer patients who received radical surgery at the Gifu University Hospital (Gifu, Japan) between 2009 and 2014 were reviewed. The axillary lymph nodes were preoperatively evaluated by PET/CT. Lymph nodes were dissected by sentinel lymph node biopsy (SLNB) or ALND and were histologically diagnosed by experienced pathologists. The maximum standardized uptake value (SUVmax) was measured in both the axillary lymph node (SUV-LN) and primary tumor (SUV-T). The SUV-LN/T ratio (NT ratio) was calculated by dividing the SUV-LN by the SUV-T, and the efficacies of the NT ratio and SUV-LN were compared using receiver operating characteristic (ROC) curve analysis. The diagnostic performance was also compared between the techniques with the McNemar test. RESULTS: A total of 171 operable invasive breast cancer patients were enrolled, comprising 69 node-positive patients (macrometastasis (Mac): n = 55; micrometastasis (Mic): n = 14) and 102 node-negative patients (Neg). The NT ratio for node-positive patients was significantly higher than in node-negative patients (0.5 vs. 0.316, respectively, P = 0.041). The NT ratio for Mac patients (0.571) was significantly higher than in Mic (0.227) and Neg (0.316) patients (P <0.01 and P = 0.021, respectively). The areas under the curves (AUCs) by ROC analysis for the NT ratio and SUV-LN were 0.647 and 0.811, respectively (P <0.01). In patients with an SUV-T ≥2.5, the modified AUCs for the NT ratio and SUV-LV were 0.757 and 0.797 (not significant). CONCLUSION: The NT ratio and SUV-LN are significantly higher in patients with axillary macrometastasis than in those with micrometastasis or no metastasis. The NT ratio and SUV-LN can help quantify axillary lymph node metastasis and may assist in macrometastasis identification, particularly in patients with an SUV-T ≥2.5.

Novel navigation surgery using image fusion of PET/CT and sonography for axillary neoplasm: First experience.

INTRODUCTION: Ultrasound sonography (US)-guided navigation systems are widely used in various organs, including the breast and liver, to locate precisely lesions that are difficult to palpate or isolate after being identified by other imaging techniques. A recent new method, "volume navigation" (Vnav), delivers real-time image fusion of US with other modalities such as MRI, CT, and PET/CT to facilitate identification and excision of suspected pathology. PRESENTATION OF CASE: The present report describes a novel navigation technique using Vnav-PET/CT, which delivers image fusion of US with PET/CT. To identify the axillary targets using Vnav-PET/CT, we set at least two landmarks then injected 0.2ml viscous blue dye in and around the capsule, which resulted in precise resection. Case 1: A 53-year-old woman with 2 PET/CT-positive lymph nodes in the right axilla underwent easy identification of the targets using the navigation technique followed by lymph node dissection. Among 32 lymph nodes dissected, only the two lymph nodes stained by blue dye were shown histologically to be malignant. Case 2: A 68-year-old woman had a PET/CT-positive lymph node in the left axilla. Vnav-PET/CT easily identified the target, which was successfully dissected under local anaesthesia. DISCUSSION: This navigation and marking using Vnav-PET/CT helped us easily approach the target, resulted in less surgical time, and avoided unsatisfactory axillary complications. These advances of the navigation system enable us to perform precise minimally invasive surgery. CONCLUSION: This is the first report of navigation surgery using Vnav-PET/CT, which may assist minimally invasive procedures, especially in the axilla.

Development of fast dissolving oral film containing dexamethasone as an antiemetic medication: clinical usefulness.

We developed a fast dissolving oral film containing 4 mg dexamethasone and examined the clinical effect of the film as the antiemetic by a randomized controlled crossover study in breast cancer patients receiving a combination chemotherapy with anthracycline and cyclophosphamide, a highly emetogenic chemotherapy. The film was prepared as reported previously using microcrystalline cellulose, polyethylene glycol, hypromellose, polysorbate 80 and 5% low substituted hydroxypropylcellulose as base materials. The uniformity of the film was shown by the relative standard deviation of 2.7% and acceptance value of 5.9% by the Japanese Pharmacopoeia. Patients were administered with 8 mg dexamethasone as oral film or tablet on days 2-4 after chemotherapy in addition to the standard antiemetic medication. The rates of complete protection from vomiting during acute and delayed phases were not different between film-treated group and tablet-treated group. The time course of the complete protection from nausea or vomiting during 0-120 h was also similar between the two groups. Patient's impressions on the oral acceptability in respect of the taste and ease in taking were significantly better for film than for tablet. Therefore, the present fast dissolving oral film containing dexamethasone seems to be potentially useful as an antiemetic agent in patients receiving highly emetogenic chemotherapy.

Growth effect of neutrophil elastase on breast cancer: favorable action of sivelestat and application to anti-HER2 therapy.

AIM: To investigate the relation between neutrophil elastase (NE) and proliferation of breast cancer cells and whether the NE inhibitor sivelestat could both contribute and be applied to therapy for anti-epithelial growth factor receptor 2 (HER2)-positive breast cancers. MATERIALS AND METHODS: The proliferation or inhibition of breast cancer cell line SKBR-3 by each agent was evaluated by methylthiazole tetrazolium (MTT) assay. Signal transduction and expression of signaling molecules were evaluated by Western blot analysis. RESULTS: The auto tumor progression mechanism initiated by NE through tumor growth factor-α (TGF-α) was present in breast cancer cells, and this mechanism was intensively suppressed by sivelestat. The effect of trastuzumab was suppressed, and trastuzumab-induced HER2 down-regulation was impaired by TGF-α. TGF-α not only promoted cell proliferation as a ligand but also enhanced resistance to trastuzumab by impairing HER2 down-regulation. Furthermore, combined use of trastuzumab and sivelestat suppressed cell proliferation more intensively than either drug alone and did not provoke impairment by TGF-α of HER2-induced down-regulation. CONCLUSION: Combinatorial use of sivelestat and trastuzumab might be a novel therapeutic strategy for HER2-positive breast cancer.

Combination therapy of 5-fluorouracil with rapamycin for hormone receptor-negative human breast cancer.

AIM: To determine a novel chemotherapeutic concept for hormone receptor-negative and HER2-positive breast cancer, a high progression form of the disease for which treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with rapamycin (Rap) was examined. MATERIALS AND METHODS: The growth inhibitory effect of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways were investigated by Western blotting and Hoechst 33342 staining. RESULTS: Rap was shown to induce an inhibitory effect on the phosphorylation of mTOR and p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay showed that apoptosis was increased by the combination of 5-FU and Rap in comparison to 5FU alone. CONCLUSION: 5-FU is more effective in combination with the TS-reducing action of Rap, even for highly HER2-expressing breast cancer cells.