Problems experienced when swallowing solid oral dosage forms in older Japanese patients with dysphagia: A cross-sectional study.

AIMS: We aimed to assess the difficulty in taking solid oral dosage forms (SODFs) among older people with dysphagia and clarify the relationship between difficulty in swallowing SODFs and swallowing function. METHODS AND RESULTS: Outpatients from a dysphagia clinic aged ≥65 years were asked yes-or-no questions about the applicability of eight items regarding difficulty in taking SODFs. Additionally, a videofluorographic swallowing study (VFSS) was performed to assess their swallowing function. The Kruskal-Wallis test and Spearman's rank correlation coefficient were used to analyze the relationship between difficulty in taking SODFs and swallowing function. RESULTS: Among the 93 participants, the average number of SODFs consumed was 5.8 ± 3.1. In the questionnaire, the average number of "yes" answers was 2.2 ± 2.2, and 65 patients (71.0%) answered "yes" to at least one question. Additionally, no significant relationship was observed between the perceived difficulty in swallowing SODFs and VFSS findings. CONCLUSION: Approximately 70% of participants reported subjective difficulty in taking SODFs, showing that patients uniformly reported perceived difficulty in taking SODFs regardless of actual swallowing function. The results of this study suggest that patients must be questioned thoroughly about their SODFs use, regardless of the objective severity of their dysphagia.

Safety and immunogenicity of BK-SE36/CpG malaria vaccine in healthy Burkinabe adults and children: a phase 1b randomised, controlled, double-blinded, age de-escalation trial.

Background: BK-SE36/CpG is a recombinant blood-stage malaria vaccine candidate based on the N-terminal Plasmodium falciparum serine repeat antigen5 (SE36), adsorbed to aluminium hydroxide gel and reconstituted, prior to administration, with synthetic oligodeoxynucleotides bearing CpG motifs. In healthy Japanese adult males, BK-SE36/CpG was well tolerated. This study assessed its safety and immunogenicity in healthy malaria-exposed African adults and children. Methods: A double-blind, randomised, controlled, age de-escalating clinical trial was conducted in an urban area of Ouagadougou, Burkina Faso. Healthy participants (n=135) aged 21-45 years (Cohort 1), 5-10 years (Cohort 2) and 12-24 months (Cohort 3) were randomised to receive three vaccine doses (Day 0, 28 and 112) of BK-SE36/CpG or rabies vaccine by intramuscular injection. Results: One hundred thirty-four of 135 (99.2%) subjects received all three scheduled vaccine doses. Vaccinations were well tolerated with no related Grade 3 (severe) adverse events (AEs). Pain/limitation of limb movement, headache in adults and fever in younger children (all mild to moderate in intensity) were the most frequently observed local and systemic AEs. Eighty-three of BK-SE36/CpG (91%) recipients and 37 of control subjects (84%) had Grade 1/2 events within 28 days post vaccination. Events considered by the investigator to be vaccine related were experienced by 38% and 14% of subjects in BK-SE36/CpG and control arms, respectively. Throughout the trial, six Grade 3 events (in 4 subjects), not related to vaccination, were recorded in the BK-SE36/CpG arm: 5 events (in 3 subjects) within 28 days of vaccination. All serious adverse events (SAEs) (n=5) were due to severe malaria (52-226 days post vaccination) and not related to vaccination. In all cohorts, BK-SE36/CpG arm had higher antibody titres after Dose 3 than after Dose 2. Younger cohorts had stronger immune responses (12-24-month-old > 5-10 years-old > 21-45 years-old). Sera predominantly reacted to peptides that lie in intrinsically unstructured regions of SE36. In the control arm, there were no marked fold changes in antibody titres and participants' sera reacted poorly to all peptides spanning SE36. Conclusion: BK-SE36/CpG was well-tolerated and immunogenic. These results pave the way for further proof-of-concept studies to demonstrate vaccine efficacy. Clinical trial registration: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1921, PACTR201701001921166.

Pounding score of intracranial lipomas.

Most intracranial lipomas are asymptomatic, but headache is the most common symptom. The pounding score is sometimes high. Therefore, it is necessary to monitor imaging findings in parallel with the treatment of migraine.

[Incidence of Secondary Malignancy of Chronic Myeloid Leukemia during Treatment of Breast Cancer with Hormone Therapy].

It is expected that the number of long-term breast cancer survivors will increase owing to the improvements in chemotherapy and irradiation, while the risk of double cancers, including secondary malignancy, may become an issue. There are many unclear points in the treatment policy with regard to when a secondary malignancy occurs or the primary cancer relapses during the management of a secondary malignancy. A 54-year-old woman who was diagnosed with ER/PgR-positive HER2 negative breast cancer Stage ⅢB received neoadjuvant chemotherapy FEC and docetaxel followed by breast surgery, adjuvant hormone therapy, and radiation therapy. Chronic myeloid leukemia diagnosed by the abnormal findings of leukocytosis and bone marrow aspiration emerged after 3 years of the diagnosis of the first breast cancer. After 3 years of imatinib therapy that achieved a major molecular response(MMR)of CML, a recurrence of sacral metastasis of breast cancer was revealed by MRI. The combination of imatinib and hormone or S-1 chemotherapy could be maintained without serious adverse events after the relapse of the primary cancer.

Breast cancer screening using digital breast tomosynthesis compared to digital mammography alone for Japanese women.

BACKGROUND: The purpose of this study is to confirm the position of DBT in breast cancer screening in Japan, to assess cancer detection rates, recall rates, positive predictive value (PPV), and to evaluate the type of mammographic findings of cancer with the use of digital mammography alone (2DDM) and combined with digital breast tomosynthesis (DBT). METHODS: 11,894 examinations of the opportunistic breast cancer screening using only 2DDM and 2DDM plus DBT were performed from May 1, 2017 to March 31, 2019. The 11,894 women [3535 women who received DBT in addition to 2DDM (3D group) and 8359 who received 2DDM only (2D group)] participated in this study. The study was approved by the Institute's Ethics Committee and all participants provided written informed consent. RESULTS: The recall rate was 2.6% for the 3D group and 3.6% for the 2D group (p < 0.01). The cancer detection rate was 0.17% in both 3D and 2D groups (p = 0.978). The positive predictive value (PPV) was 6.5% for the 3D group and 4.7% for the 2D group (p = 0.484). The cause of the decrease in recall rate was due to a decrease in the finding of focal asymmetric density (FAD). CONCLUSION: The recall rate was improved by using DBT for breast cancer screening in Japanese women. Cancer detection rates were exactly the same in DBT and 2DDM groups, so only DBT non-inferiority could be verified. We have verified that breast cancer screening combined with DBT is useful even for Japanese women to reduce unnecessary further examination.

[A Case of Ipsilateral Breast Tumor Recurrence(IBTR)after Breast-Conserving Surgery Which Successfully Resected after Chemotherapy Using Carboplatin plus Gemcitabine].

A 39-year-old woman underwent partial mastectomy with sentinel lymph node biopsy for right triple negative breast cancer(T2N0M0, Stage ⅡA). Six months later, ipsilateral breast tumor recurrence(IBTR)was observed and paclitaxel plus bevacizumab therapy was started, but anaphylactoid symptoms appeared and the patient was discontinued. Subsequently, eribulin was started, but the IBTR was increased ineffectively. At that point, IBTR had progressed, apparently unresectable, with no distant metastases. We predicted from the patient's background that the patient may be associated with BRCA1 gene mutation and was sensitive to the platinum salts. Carboplatin plus gemcitabine was selected and 6 courses were performed. After the 6 courses, the IBTR were remarkably reduced and resectable, and mastectomy with axillary lymph node dissection were performed. One year after the operation, contralateral breast cancer develop and found to be hereditary breast and ovarian cancer syndrome (HBOC) by Genetic test. About 6 years have passed since local recurrence, but no distant metastases have been observed.

[A Case of Recurrent Premenopausal Hormone Receptor Positive Breast Cancer with Liver, Lung and Bone Metastasis Successfully Treated with Endocrine Therapy].

Here we report a 48-year-old female with recurrent breast cancer. She had received chest muscle-conserving mastectomy and lymph node dissection at another hospital, diagnosed as pStage ⅡB, T2N1M0 premenopausal left endocrine positive/ HER2 negative breast cancer at the age of 45. Although postoperative adjuvant therapy was started with LH-RH agonist plus tamoxifen, and chest radiation, tamoxifen therapy was intolerantly discontinued due to severe adverse events of hot flash after 1 year later. Three years later, she presented with back pain and was referred to our hospital. As PET-CT revealed recurrence of multiple bone and lung metastases and solitary liver metastasis which did not seem to be life-threatening, palliative radiation therapy and endocrine therapy with leuprorelin and anastrozole(LA)were started. Eighteen months later, PET-CT showed complete disappearance of liver and lung metastases and remarkable regression of bone metastases except for the right sciatic bone. LA therapy could be maintained for a total of 30 months until metastatic recurrence on liver and bone emerged. LA endocrine therapy may be effective for patients with premenopausal hormone-positive breast cancer even if the difficult situation such as tamoxifen intolerance.

Randomized Multicenter Phase II Trial of Neoadjuvant Therapy Comparing Weekly Nab-paclitaxel Followed by FEC With Docetaxel Followed by FEC in HER2- Early-stage Breast Cancer.

BACKGROUND: Weekly nanoparticle albumin-bound paclitaxel (nab-paclitaxel) demonstrated greater efficacy with less toxicity than docetaxel in metastatic breast cancer. We conducted a randomized phase II to compare these regimens as neoadjuvant chemotherapy for HER2- early-stage breast cancer. PATIENTS AND METHODS: Stage I-III human epidermal growth factor receptor-negative (HER2-) breast cancer patients were included in the present trial and received either docetaxel every 3 weeks or nab-paclitaxel on days 1, 8, and 15 every 28 days for 4 cycles, followed by FEC (5-fluorouracil, epirubicin, cyclophosphamide) every 3 weeks for 4 cycles. The primary endpoint was the pathologic complete response (pCR) rate, defined as ypT0 and ypN0. The secondary endpoints were pCR (ypT0/ypTis and ypN0), the clinical response rate (using the Response Evaluation Criteria In Solid Tumors criteria), histologic effect of treatment (using the Japanese Breast Cancer Society classification), breast conservation rate, and adverse events. RESULTS: A total of 152 eligible patients were enrolled at 6 centers. The baseline characteristics were well balanced. In comparing the 2 regimens (docetaxel/nab-paclitaxel), the pCR rate was 12% and 17% (P = .323). In the Ki67 > 20% group, the pCR rate was greater (24%) for the nab-paclitaxel arm than for the docetaxel arm (16%; P = .432). The most common grade 3/4 adverse event was neutropenia, observed in 40% and 36% of cases in the nab-paclitaxel and docetaxel arms, respectively. The nonhematologic adverse events of any grade were myalgia (34% and 32%), arthralgia (42% and 35%), and peripheral sensory neuropathy (55% and 65%) for the 2 treatment arms. No grade 3/4 peripheral sensory neuropathy was observed in the nab-paclitaxel arm. CONCLUSION: Weekly nab-paclitaxel administered at a dose of 100 mg/m2 showed equivalent efficacy and was well tolerated compared with docetaxel as neoadjuvant therapy. Nab-paclitaxel might be more effective in patients with highly proliferative cancer.

Clinicopathological relevance of kinesin family member 18A expression in invasive breast cancer.

Recently, kinesin motor proteins have been focused on as targets for cancer therapy. Kinesins are microtubule-based motor proteins that mediate diverse functions within the cell, including the transport of vesicles, organelles, chromosomes and protein complexes, as well as the movement of microtubules. In the current study, the expression of kinesin family member 18A (KIF18A), a member of kinesin superfamily, was investigated in breast cancer using immunohistochemistry, and its effect on breast cancer prognosis was examined. KIF18A expression level was significantly associated with lymph node metastasis (P=0.047). In patients with high levels of KIF18A expression, survival was significantly poorer compared to patients with low levels of KIF18A expression (disease-free survival, P=0.030). Multivariate analysis revealed that venous invasion (hazard ratio, 9.22; 95% confidence interval, 3.90-23.66; P<0.001) and KIF18A expression (hazard ratio, 3.20; 95% confidence interval, 1.34-6.09; P=0.010) were independent predictive factors for lymph node metastasis. KIF18A may be a useful predictive marker for lymph node metastasis in breast cancer, which could facilitate curative adjuvant treatment.

Vertigo by Breast Cancer Metastasis 33 Years after Treatment.

A 76-year-old woman complained of vertigo for two years. She manifested left deafness, loss of caloric response, and right-beaten nystagmus. An imaging study revealed a tumorous lesion located from the clivus to the left temporal bone with inner ear destruction. A tumor biopsy was performed endonasally and the patient was diagnosed with adenocarcinoma mimicking breast cancer. She had undergone surgery for breast cancer 33 years previously, and the current biopsy specimen showed identical pathology. Breast cancer may metastasize to the skull base; however, metastasis 33 years after surgery is very rare.

Nipple malposition after nipple-sparing mastectomy and expander-implant reconstruction.

BACKGROUND: Nipple malposition after nipple-sparing mastectomy and expander-implant reconstruction performed in our institute between 2002 and 2010 was studied retrospectively, targeting breast ptosis and volume. METHODS: The preoperative nipple position relative to the inframammary fold was used as the breast ptosis index. The intraoperative resected breast tissue was measured and used as the volume index. For pre- and postoperative photograph evaluation, the vertical distance of the nipple was defined as the distance from the nipple to the midpoint of the bottoms of the sternocleidomastoid muscle. The vertical distance ratio was defined as the postoperative affected-side/unaffected-side vertical distance to the preoperative one. A correlation analysis was carried out comparing the vertical distance ratios with the preoperative nipple position relative to the inframammary fold and resection tissue weight. RESULTS: A total of 42 cases using the expander-implant method were analyzed. The mean vertical distance ratio was 0.88. There was a comparatively high correlation between the vertical distance ratio and the resection tissue weight (correlation coefficient -0.53, P = 0.0003) and between the vertical distance ratio and the preoperative nipple position relative to the inframammary fold (correlation coefficient 0.37, P = 0.0152). CONCLUSION: In expander-implant reconstruction of a large or ptotic breast, nipple-sparing mastectomy should be performed with the expectation that ancillary procedures will be needed.

[MASTECTOMY AND BREAST-CONSERVING SURGERY].

Mastectomy and breast-conserving surgery (BCS) are common procedures for treating breast cancer at present. The discovery rate of tumors 2 cm or less in size has risen with the increase in the number of women who receive breast physical examinations, and because of the wider usage of preoperative chemotherapy, BCS has become possible. As a result, the number of women undergoing BCS has increased, whereas the number of those undergoing mastectomy has decreased. However, if radical cure or good cosmetic results cannot be achieved, mastectomy is often offered to patients. Recently, patients have come to expect good cosmetic results after BCS, and because breast reconstruction with implants is now covered by health insurance, it is possible to perform it with mastectomy with the help of plastic surgery if patients desire. Oncoplastic surgery is now the focus of public attention, because it differs from conventional BCS in that it results in no deformity, since the defect created by wide resections is filled with a local tissue flap. It is psychologically important for patients to have satisfactory cosmetic results after BSC.

Clinicopathologic relevance of claudin 5 expression in breast cancer.

OBJECTIVES: Claudins are major adhesion molecules in tight junctions and are strongly expressed in various cancers. We thus investigated the expression of claudin 5, a member of the claudin family, in breast cancer. METHODS: A total of 193 patients with breast cancer were identified based on their pathologic diagnosis. The expression of each claudin 5 was analyzed in the tumor by immunohistochemical staining. Parametric correlations were done between claudin 5 expression and the clinicopathologic findings. RESULTS: Claudin 5 expression in patients with recurrent breast cancer was statistically significantly higher (P = .004). In addition, analysis of the correlation with other clinicopathologic factors showed statistically significant differences with respect to lymphatic invasion (P = .014), venous invasion (P = .048), estrogen receptor status (P = .002), and human epidermal growth factor 2 status (P = .007). Multivariate analysis revealed that claudin 5 expression was an independent predictive factor in the recurrence for relapse-free survival (RFS) (P = .020). Kaplan-Meier analysis showed that the RFS rate was significantly lower in the high claudin 5 expression group (P = .001). CONCLUSIONS: Patients with breast cancer with high claudin 5 expression had a significantly lower RFS rate. Our findings suggest that claudin 5 may be useful as a new biomarker of a risk factor.

Efficiency of fluorodeoxyglucose positron emission tomography/computed tomography to predict prognosis in breast cancer patients received neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) has become a standard therapy for patients with advanced breast cancer. Pathological complete response (pCR) after NAC is an important prognostic indicator, but some patients with pCR continue to experience recurrence. So new predictive and prognostic markers in addition to pCR are needed following NAC for breast cancer. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can evaluate metastases in the entire body simultaneously, and has several potential advantages over conventional imaging modalities. The purpose of this study was to evaluate whether FDG-PET/CT can determine NAC response and whether FDG-PET/CT can be a new prognostic marker. We imaged 83 breast cancer tumors with FDG-PET/CT, ultrasound (US), and magnetic resonance imaging (MRI) to evaluate NAC efficacy. As we previously analyzed 110 breast cancers with FDG PET/CT, we defined a threshold of >1.7 maximum standardized uptake value (SUVmax) as abnormal fluorodeoxyglucose (FDG) uptake. After NAC, 16 (19.3 %) tumors had a complete response, 54 (65.1 %) had a partial response, 11 (13.3 %) showed stable disease, and 2 (2.4 %) showed progressive disease. One of the two patients with progressive disease had bone metastasis detected by FDG-PET/CT and was not operated on. Remote metastases were evident in 2.4 % of patients after NAC as determined by FDG-PET/CT. Overall, 17 patients had pathological complete response (pCR). The sensitivity of abnormal FDG uptake after NAC for non-pCR was 20.3 % and the specificity was 94.7 %. Patients with abnormal FDG uptake after NAC experienced significantly more recurrences (P = 0.004) and more of them died (P = 0.010). Moreover, the difference in disease-free survival was more significant in the estrogen receptor (ER)-negative group. FDG-PET after NAC may be more effective for predicting prognosis than for evaluating treatment response. This tendency was particularly remarkable in ER-negative breast cancer tumors. FDG-PET/CT is useful for reevaluating surgical applicability after NAC.

Periostin suppression induces decorin secretion leading to reduced breast cancer cell motility and invasion.

The ability of cancer cells to metastasize is dependent on the interactions between their cell-surface molecules and the microenvironment. However, the tumor microenvironment, especially the cancer-associated stroma, is poorly understood. To identify proteins present in the stroma, we focused on phyllodes tumors, rare breast tumors that contain breast stromal cells. We compared the expression of proteins between phyllodes tumor and normal tissues using an iTRAQ-based quantitative proteomic approach. Decorin was expressed at reduced levels in phyllodes tumor tissues, whereas periostin was upregulated; this result was validated by immunohistochemical analysis of phyllodes tumors from 35 patients. Additionally, by immunoprecipitation and mass spectrometry, we confirmed that decorin forms a complex with periostin in both phyllodes tumors and BT-20 breast cancer cells. Following siRNA-mediated knockdown of periostin in T-47D cells, secreted decorin in the culture medium could be detected by multiple reaction monitoring (MRM). Furthermore, periostin knockdown in BT-20 cells and overexpression of decorin in MDA-MB-231 cells inhibited cell motility and invasion. Our results reveal the molecular details of the periostin-decorin complex in both phyllodes tumor tissues and breast cancer cells; this interaction may represent a novel target for anti-cancer therapy.

Analysis of nitrification in agricultural soil and improvement of nitrogen circulation with autotrophic ammonia-oxidizing bacteria.

Accumulations of inorganic nitrogen (NH4⁺, NO2⁻, and NO3⁻) were analyzed to evaluate the nitrogen circulation activity in 76 agricultural soils. Accumulation of NH4⁺ was observed, and the reaction of NH4⁺→ NO2⁻ appeared to be slower than that of NO2⁻ → NO3⁻ in agricultural soil. Two autotrophic and five heterotrophic ammonia-oxidizing bacteria (AOB) were isolated and identified from the soils, and the ammonia-oxidizing activities of the autotrophic AOB were 1.0 × 10³-1.0 × 106 times higher than those of heterotrophic AOB. The relationship between AOB number, soil bacterial number, and ammonia-oxidizing activity was investigated with 30 agricultural soils. The ratio of autotrophic AOB number was 0.00032-0.26% of the total soil bacterial number. The soil samples rich in autotrophic AOB (>1.0 × 104 cells/g soil) had a high nitrogen circulation activity, and additionally, the nitrogen circulation in the agricultural soil was improved by controlling the autotrophic AOBs.

Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable.

Phospholipase D (PLD), which produces the lipid messenger phosphatidic acid (PA), has been implicated in superoxide generation and degranulation in neutrophils. The basis for this conclusion is the observation that primary alcohols, which interfere with PLD-catalyzed PA production, inhibit these neutrophil functions. However, off-target effects of primary alcohols cannot be totally excluded. Here, we generated PLD(-/-) mice in order to reevaluate the involvement of PLD in and investigate the molecular mechanisms of these neutrophil functions. Surprisingly, N-formyl-methionyl-leucyl-phenylalanine (fMLP) induced these functions in PLD(-/-) neutrophils, and these functions were suppressed by ethanol. These results indicate that PLD is dispensable for these neutrophil functions and that ethanol nonspecifically inhibits them, warning against the use of primary alcohols as specific inhibitors of PLD-mediated PA formation. The calcium ionophore ionomycin and the membrane-permeative compound 1-oleoyl-2-acetyl-sn-glycerol (OADG) synergistically induced superoxide generation. On the other hand, ionomycin alone induced degranulation, which was further augmented by OADG. These results demonstrate that conventional protein kinase C (cPKC) is crucial for superoxide generation, and a Ca(2+)-dependent signaling pathway(s) and cPKC are involved in degranulation in mouse neutrophils.

Molecular mechanisms of fMLP-induced superoxide generation and degranulation in mouse neutrophils.

In this manuscript, involvement of PLD in fMLP-induced superoxide generation and degranulation were re-investigated using PLD(-/-) neutrophils, and the molecular mechanisms of these neutrophil functions were examined. Neither PLD1 nor PLD2 is involved in these fMLP-induced neutrophil functions. The results obtained in this study provide evidence that cPKC plays an important role in fMLP-induced superoxide generation. On the other hand, Ca(2+)-dependent signaling pathway and cPKC seem to be involved in degranulation.

[A case of T4bN3c breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after systemic chemotherapy].

A 40 year-old woman had right T4bN3c breast cancer without distant metastasis. A partial response was achieved in the primary lesion and right supraclavicular and axillary lymph node involvement was no longer noted after systemic chemotherapy (weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide [FEC]). The patient wished to undergo immediate reconstruction of the right breast, and therefore, modified radical mastectomy with tissue expander reconstruction was performed. Adverse effects due to chemotherapy were of Grade 2. Six months after post-mastectomy radiation therapy, the tissue expander was removed and the right breast was reconstructed using an implant. No complications were noted. Six years have passed since the operation, and no local recurrence or distant metastasis has been noted. In addition, the cosmetic appearance of the right breast is satisfactory.

[A case of recurrent breast cancer with carcinomatous pleurisy responding to bevacizumab and paclitaxel therapy].

A 57-year-old woman who had undergone muscle-preserving radical mastectomy at the age of 38 presented with a 5 cm mass in front of the breastbone. She was diagnosed as having recurrent breast cancer( estrogen receptor[ ER] positive, progesterone receptor[ PgR] positive, human epidermal growth factor receptor[ HER] -2 negative) by core needle biopsy. She received an aromatase inhibitor (AI) and showed partial response. At the age of 54, PgR status became negative. At the age of 55, the recurrent tumor increased in size, and the patient received 50 Gy of radiation therapy for its treatment and AI administration was continued. At the age of 57, tumor marker levels increased and detailed examination revealed that the recurrent tumor had increased in size and carcinomatous pleurisy was noted. Bevacizumab and paclitaxel therapy was initiated. Tumor marker levels decreased and the pleural fluid disappeared in 2 weeks. After 3 courses, positron emission tomography( PET) -computed tomography( CT) showed a reduction in the tumor size and a decrease in fluorodeoxyglucose (FDG) uptake. Bevacizumab and paclitaxel therapy could be effective for the treatment of patients with recurrent breast cancer with a life-threatening status, after hormone therapy failure. Bevacizumab and paclitaxel could be effective as first- line chemotherapy because of its good treatment efficiency.