Vimentin-positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics.

Vimentin is a stable mesenchymal immunohistochemical marker and is widely recognized as a major marker of mesenchymal tumors. The purpose of the present study was to investigate if the vimentin expression status might serve as a significant predictor of outcomes in patients with invasive breast carcinoma of no special type (IBC-NST) and to investigate, by comprehensive RNA sequencing analyses, the mechanisms involved in the heightened malignant potential of vimentin-positive IBC-NSTs. This study, conducted using the data of 855 patients with IBC-NST, clearly identified vimentin expression status as a very important independent biological parameter for accurately predicting the outcomes in patients with IBC-NST. RNA sequence analyses clearly demonstrated significant upregulation of coding RNAs known to be closely associated with cell proliferation or cellular senescence, and significant downregulation of coding RNAs known to be closely associated with transmembrane transport in vimentin-positive IBC-NSTs. We conclude that vimentin-positive IBC-NSTs show heightened malignant biological characteristics, possibly attributable to the upregulation of RNAs closely associated with proliferative activity and cellular senescence, and downregulation of RNAs closely associated with transmembrane transport in IBC-NSTs.

Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review.

BACKGROUND: Primary hepatic adenosquamous carcinoma (ASC) is a type of tumor that has the features of both adenocarcinoma and squamous cell carcinoma (SCC). The prognosis for patients with ASC is poor, as the chemotherapy has been ineffective so far. CASE PRESENTATION: Here, we report a case of a 62-year-old male patient who presented with high fever. The tumor marker levels were high, and abdominal dynamic computed tomography showed a liver tumor and distant lymph node metastases. Upon further investigation, needle biopsy of the liver tumor showed a primary hepatic SCC. Because the SCC was unresectable, the patient was treated with tegafur/gimeracil/oteracil (S-1) and transcatheter hepatic arterial injection (TAI) of cisplatin. After chemotherapy, a surgical resection performed on the remaining liver tumor, made the patient cancer-free. After the operation, the liver tumor was confirmed as primary hepatic ASC. Subsequently, the patient was administered postoperative adjuvant chemotherapy, which prevented its recurrence. CONCLUSIONS: Due to the lack of an effective treatment for primary hepatic ASC, its prognosis is poor. Here, we suggest that a chemotherapy combination of 5-fluorouracil (S-1) and cisplatin along with conversion surgery might be an effective way for treating primary hepatic ASC. Our experience from this case shall be valuable to clinicians around the world involved in the treatment of primary hepatic ASC.

Changes in disease characteristics of primary biliary cholangitis: An observational retrospective study from 1982 to 2016.

AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

[Clinical Outcomes of Five Cases of Occult Breast Cancer in Which the Primary Site Was Not Detected in the Breast-by-Breast MRI].

Occult breast cancer is rare in practice. We studied the clinical outcomes of 5 occult breast cancers, including 2 with Luminal and 3 with non-Luminal subtypes, for which the primary site was not detected in the breast-by-breast MRI. The percentage of occult breast cancers that we encountered at our hospital was 0.11%. The mean age was 54 years. The Ki-67 labeling index value was 30% or higher for all the patients except one. Four patients were administered neoadjuvant chemotherapy and all but one patient received non-mastectomy and axillary dissection plus radiotherapy. We observed recurrent cases in one example each of the Luminal and HER2 subtypes, and both patients were less than 40 years old. The estimates of the probability of 5 year recurrence-free survival and 5 year overall survival were 40.0% and 66.7%, respectively. One recurrence case was a patient negative for ER and positive for HER2 wherein a breast cancer lesion appeared in the breast during post-treatment follow-up. Intrabreast relapse, which is itself rare in occult breast cancer, was observed 4 years postoperatively after standard treatment. Although there was no deviation according to subtype rate, the Ki-67 labeling index value was high and the prognosis was poor in our 5 cases.

[Patient with Recurrent Breast Cancer Who Developed Radiation Esophagitis with Severe Esophageal Stenosis after Combined Bevacizumab and Paclitaxel Therapy-A Case Report].

Severe stenosis rarely occurs with radiation esophagitis after irradiation. We report our recent experience of a case of recurrent breast cancer in which the patient developed severe esophageal stenosis after receiving combined bevacizumab (Bev)-paclitaxel(PTX)therapy following radiotherapy for a thoracic vertebral metastasis. A 59-year-old woman with Stage ⅢB left breast cancer had undergone total mastectomy with axillary lymph node dissection after receiving neoadjuvant therapy. Elevated carcinoembryonic antigen levels were observed 23 months postoperatively, and multiple bone metastases were detected on PET-CT. After 5 sessions of irradiation with 20 Gy at the Th8-L1 level, combined Bev and PTX plus zoledronic acid was administered. The patient developed dysphagia at the end of the 4 cycles of combined Bev and PTX therapy, and her condition exacerbated subsequently. Therefore, upper gastrointestinal endoscopy was performed, which revealed a circumferential stenosis 31-37 cm from the incisors. We decided to perform the endoscopic treatment. After 3 balloon dilatations, her condition improved, and oral ingestion was possible. The esophageal stenosis might have been caused by the exacerbation of esophagitis because of the delayed wound healing effect of Bev in addition to radiation.

[A case of liver abscess caused by hypermucoviscous Klebsiella pneumoniae with septic pulmonary embolism].

A 69-year-old man consulted a local doctor because of a chief complaint of fever and anorexia. CT showed a giant liver mass of the right hepatic lobe and multiple pulmonary nodules. The patient was admitted to our hospital. We punctured the liver mass, obtaining pus, and as gram-negative bacilli were detected from both blood and pus cultures, a liver abscess with septic pulmonary embolism was diagnosed. Following a positive string test, we identified the pathogenic bacteria as hypermucoviscous Klebsiella pneumoniae, which is highly invasive to the tissues. The patient showed improvement following the administration of an antimicrobial agent (Meropenem) and multiple abscess drainage procedures.

A dose-finding randomized Phase II study of oral netupitant in combination with palonosetron .75 mg intravenous for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving highly emetogenic chemotherapy.

OBJECTIVE: Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose-response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy. METHODS: Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2-4). RESULTS: Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0-120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose-response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg. CONCLUSIONS: No dose-response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed. CLINICAL TRIAL REGISTRATION: JapicCTI-142 483.

Correction to: Intracellular hypoxia measured by F-18 fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen-receptor positive breast (BRCR-D17-00693).

After the publication of this article [1], we noticed that in Fig. 2, the survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2 is presented below. The correction does not affect in any our results and conclusions.

Intracellular hypoxia measured by 18F-fluoromisonidazole positron emission tomography has prognostic impact in patients with estrogen receptor-positive breast cancer.

BACKGROUND: Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of 18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. METHODS: Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with 18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. RESULTS: Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8. CONCLUSIONS: FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000006802 . Registered on 1 December 2011.

Fibrotic focus: An important parameter for accurate prediction of a high level of tumor-associated macrophage infiltration in invasive ductal carcinoma of the breast.

Our group and others have previously reported that a fibrotic focus is a very useful histological factor for the accurate prediction of the outcome of patients with invasive ductal carcinoma of the breast. We classified 258 cases of invasive ductal carcinoma into those with and those without a fibrotic focus to investigate whether the presence of a fibrotic focus was significantly associated with the degree of tumor-associated macrophage (CD68, CD163 or CD204-positive) infiltration or whether the presence of tumor-associated macrophage infiltration heightened the malignant potential of invasive ductal carcinoma with a fibrotic focus. Multiple regression analyses demonstrated that a fibrotic focus was the only factor that was significantly associated with a high level of CD68-, CD163- or CD204-positive tumor-associated macrophage infiltration. The combined assessment of the presence or absence of a fibrotic focus and a high or a low level of CD204-positive tumor-associated macrophage infiltration clearly demonstrated that CD204-positive tumor-associated macrophage infiltration had a significant prognostic power only for patients with invasive ductal carcinoma with a fibrotic focus in multivariate analyses; CD204-positive tumor-associated macrophages might only exert a significant effect on tumor progression when a fibrotic focus is present within the invasive ductal carcinoma of the breast.

Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety.

BACKGROUND: This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer. METHODS: Patients with HER2-positive, stage I-III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m2, day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks. The primary endpoint was pathological complete response (pCR) of both breast and axillary lymph node disease. RESULTS: Fifty patients were enrolled in this study. Median age was 58 (range 32-75) years. All patients underwent definitive surgery. Thirty-three (66%) patients completed the chemotherapy course, while the treatment was delayed or discontinued in the other 17 (34%) patients because of adverse events (AEs). The pCR rate was 52%; the overall response rate was 66%. Grade 3/4 AEs due to nonhematological toxicity were anorexia (4%), diarrhea (2%), and rash (2%), and those due to hematological toxicity were neutropenia (36%), anemia (12%), and thrombocytopenia (2%). CONCLUSION: Although the triweekly six-course regimen of TCbH achieved a high pCR rate, hematological AEs frequently occurred during the latter part of the chemotherapy course. One-third of patients experienced delayed or discontinued chemotherapy. Clinical registration number: http://www.umin.org.au UMIN000013513.

TRIM44 Is a Poor Prognostic Factor for Breast Cancer Patients as a Modulator of NF-κB Signaling.

Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade (p = 0.033), distant disease-free survival (p = 0.031) and overall survival (p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival (p = 0.005) and overall survival (p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT-PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling.

In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: a comparison to bevacizumab.

BACKGROUND: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents. METHODS: Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO2) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies. RESULTS: Baseline DOSI measurement of all 29 patients (eribulin, n=14 and bevacizumab, n=15) revealed significantly higher tumour concentrations of O2Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O2Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF-ß1. CONCLUSIONS: Eribulin, but not bevacizumab, treatment increased tumour SO2. Suppression of TGF-ß1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.

Comparison of visual assessment and image analysis in the evaluation of Ki-67 expression and their prognostic significance in immunohistochemically defined luminal breast carcinoma.

OBJECTIVES: To compare the Ki-67 labeling index value obtained through immunohistochemistry analysis by human examiners to that obtained from computer-assisted image analysis, and to establish a cut-off value for Ki-67 labeling index for each method in luminal B breast carcinoma. METHODS: Immunohistochemistry analysis for Ki-67 was performed on the formalin-fixed, paraffin-embedded tissue samples from 403 patients with primary luminal breast cancers. Whole slide images were obtained using the NanoZoomer (Hamamatsu Photonics, Hamamatsu, Japan) and thoroughly analyzed using the Definiens Tissue Studio version 1.1 (Definiens AG, Munich, Germany) to detect the percentage of positively-stained nuclei of carcinoma cells. RESULTS: Although a significant correlation was found between the Ki-67 labeling index obtained by manual assessment and computer-assisted image analysis (Spearman rank correlation coefficient, P < 0.01), the Ki-67 labeling index value obtained by manual assessment was significantly higher than that obtained by computer-assisted image analysis (Wilcoxon signed rank test, P < 0.0001). Disease-free survival was significantly lower in 403 patients with tumors having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.00001) and visual counting (cut-off value: 28.5%; P < 0.00001). Disease-free survival was also significantly lower in 288 patients who received adjuvant endocrine therapy alone having high Ki-67 labeling index values determined by automated analysis (cut-off value: 11.5%; P < 0.0001) and visual counting (cut-off value: 19.7%, P < 0. 0001). CONCLUSIONS: The Ki-67 labeling index values determined by automated analysis and visual counting could equally predict disease-free survival in patients with luminal B breast carcinoma, including those who received endocrine therapy.

Jejunal varices after choledochojejunostomy treated with laparotomic transcatheter variceal embolization.

Portal hypertension induces collateral shunt formation between the portal and systemic circulation, decompressing the elevated portal pressure. Ectopic varices outside of the gastroesophageal region, such as jejunal varices, are rare conditions. This report describes the successful embolization of ruptured jejunal varices resulting from an extrahepatic portal obstruction. A 62-year-old man was admitted to our hospital with recurrent massive gastrointestinal bleeding. Fourteen months earlier, he had undergone a choledochojejunostomy and pancreatic cystojejunostomy for bile duct stenosis with an enlarged pancreatic pseudocyst due to severe chronic pancreatitis. Contrast-enhanced computed tomography showed jejunal intramural dilated vessels close to the choledochojejunal anastomosis, but extravasation was not observed. Due to the lack of a rapid definitive diagnosis, the patient required massive blood transfusions. Hemorrhagic scintigraphy using 99mTc-HSAD finally identified the site of the hemorrhage. Angiography and double-balloon endoscopy revealed the anastomotic jejunal varices to be the result of an extrahepatic portal obstruction. Laparotomic transcatheter variceal embolization with microcoils was successful in halting the refractory gastrointestinal bleeding. This surgery preserved hepatopetal portal venous flow by another route, and no complications were observed. At present, 4 years post-surgery, there has been no recurrence of gastrointestinal hemorrhage. The development of jejunal varices is often associated with postoperative adhesions. Some patients with a history of hepatico- or choledochojejunostomy may experience portal hypertension resulting from extrahepatic portal obstruction, leading to the formation of jejunal varices as hepatopetal portal collaterals. The choice of therapy in each patient should be based on the individual hemodynamics of the ectopic varices.

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety.

OBJECTIVE: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. METHODS: Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. RESULTS: Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. CONCLUSION: Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management.

[Progress in second-line therapies for metastatic breast cancer].

It may be difficult to achieve complete cure for most metastatic breast cancer patients;thus, prolongation of overall survival and maintenance of the quality of life are often the main focus of treatment. In the treatment of metastatic breast cancer patients, it is important to choose the most appropriate therapeutic strategy based on substantial evidence that considers the biology of the tumor, including estrogen receptor(ER), progesterone receptor(PgR), and human epidermal growth factor receptor 2(HER2)status;the site and extent of the metastatic focus;the time to recurrence;prior treatment regimens;age; menopausal status;performance status;and the preference of the patient. A clinical subtype classification that is based on the tumor biology is typically utilized for devising a treatment strategy specific to each subtype. Expressly, first-line treatment options may include hormone therapy for hormone-positive breast cancers, antiHER2 therapy for HER2-positive breast cancers, and chemotherapy for hormone-negative and HER2-negative(triple negative)breast cancers. In recent years, with the development of regimens that are effective for every subtype, the treatments for breast cancer have undergone significant changes. In this section, we introduce the progress in the treatment for metastatic breast cancer, focusing specifically on second-line therapies according to each subtype.

Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy.

Near-infrared diffuse optical spectroscopy (DOS) imaging can non-invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time-resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2 ) of the tumors was compared with clinicopathological variables and 10-year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis . Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10-year relapse-free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.