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Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC).Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2–4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)–objective response rate according to volumetric response criteria.Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33–75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9–89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ≥80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5–8.1) and 10.5 months (95% CI, 7.8–13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%).Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. Clin Cancer Res; 21(8); 1851–8. ©2015 AACR.

Supplementary figure 1. Kaplan-Meier survival curves of patients who completed 6 cycles of BEEP regimen, categorized by whether received further bevacizumab-based maintenance treatment.

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Purpose Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. MethodsA total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical pathologic characteristics, survival and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. Results The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years-old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, pBRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. ConclusionOur study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.

Yi-Ping Weng,1,2 Rei-Mei Hong,2 Vincent Chin-Hung Chen,3,4 Chia-Jui Tsai,5,6 Dah-Cherng Yeh,7 Yu-Hung Fang8 1Department of Nursing, Chia-Yi Chang Gung Memorial Hospital, Chiayi branch, Puzi City, Chiayi County, Taiwan, R.O.C; 2Department of Nursing, Chia-Yi Chang Gung University of Science and Technology, Chiayi branch, Puzi City, Chiayi County, Taiwan, R.O.C; 3Department of Psychiatry, Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Chiayi branch, Puzi City, Chiayi County, Taiwan, R.O.C; 4School of Medicine, Chang Gung University, Taoyuan City, Taiwan, R.O.C; 5Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C; 6Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C; 7Breast Medical Center, Cheng Ching Hospital, Chung Kang Branch, Taichung City, Taiwan, R.O.C; 8Division of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch, Puzi City, Chiayi County, 61363, Taiwan, R.O.CCorrespondence: Yu-Hung FangDivision of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi branch, No.6, W. Sec., Jiapu Rd, Puzi City, Chiayi County, 61363, Taiwan, R.O.CTel +886-5-362-1000 ext. 2762Fax +886-5-362-3005Email 8902062@adm.cgmh.org.twBackground: Sleep disturbances are common and symptomatic burden in patients with breast cancer, but they are poorly documented and managed in routine clinical practice. This descriptive and cross-sectional study evaluated factors associated with post-treatment sleep disturbances in patients with breast cancer.Patients and Methods: Patients with breast cancer who underwent standard treatment were enrolled and surveyed for their basic demographic data and precancerous and cancer treatment-related factors; they were also administered self-report questionnaires including the Family Adaptation, Partnership, Growth, Affection, Resolve questionnaire; Impact of Event Scale; Center for Epidemiologic Studies Depression Scale; and Maudsley Personality Inventory. Their sleep disturbances were evaluated using the Pittsburgh sleep quality index (PSQI). Independent sample t test and chi-square tests were used to compare the variables between patients with or without sleep disturbance, and multivariate logistic regression analyses were conducted to detect the independent factors.Results: In total, 448 patients, including 145 with PSQI ≤ 5 and 303 with PSQI > 5, completed the investigation. Multiple logistic regression analysis revealed that significantly more patients with sleep disturbances demonstrated psychological distress, severe pain, depression, and impact of stress events than patients without sleep disturbances (adjusted odds ratios [95% confidence intervals]: 2.83 [1.135– 7.067], P = 0.026; 1.14 [1.023– 1.280], P = 0.018; 1.08 [1.036– 1.133], P < 0.001; and 1.03 [1.002– 1.051], P = 0.037, respectively).Conclusion: Patients with breast cancer showed 67.6% prevalence of sleep disturbances after treatment. The patients with sleep disturbances were more likely to have previously experienced psychological disturbances, severe pain, depression within 5 years after diagnosis. After diagnosis for more than 5 years, higher distress caused by traumatic events still associated with sleep disturbances.Keywords: sleep disturbance, breast cancer, depression, pain, post-traumatic stress disorder, symptoms cluster

The OlympiAD Phase III study (NCT02000622) established the clinical benefits of olaparib tablet monotherapy (300 mg twice daily) over chemotherapy treatment of physician’s choice (TPC) in patients with a germline BRCA1/2 mutation (gBRCAm) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who had received ≤2 chemotherapy lines in the metastatic setting. Here, we report pre-specified analyses of data from Asian (China, Japan, Korea and Taiwan) patients in the study. All patients were randomized 2:1 to olaparib tablets (300 mg twice daily) or single-agent chemotherapy TPC (21-day cycles of either capecitabine, eribulin or vinorelbine). The primary endpoint was progression-free survival assessed by blinded independent central review. The prevalence of gBRCAm in the OlympiAD Asian subgroup screened for study recruitment was 13.5%. Patient demographics and disease characteristics of the Asian subgroup (87/302 patients) were generally well balanced between treatment arms. Asian patients in the olaparib arm achieved longer median progression-free survival, assessed by blinded independent central review, versus the chemotherapy TPC arm (5.7 vs 4.2 months; HR = 0.53 [95% CI: 0.29–0.97]), which was consistent with findings in the global OlympiAD study population. Findings on secondary efficacy and safety/tolerability outcome measures in Asian patients were also similar to those observed in the global OlympiAD study population. The OlympiAD study was not powered to detect race-related differences between treatment groups; however, the consistency of our findings with the global OlympiAD study population suggests that previously reported findings are generalizable to Asian patients.

Background: Adjuvant whole breast radiotherapy is the standard of care for breast cancer patients after partial mastectomy. Intensity-modulated radiation therapy (IMRT) has been reported to reduce acute toxicities compared to conventional radiotherapy. IMRT with simultaneous integrated boost (SIB) technique can deliver higher doses to tumor bed and irradiate whole breast with a lower dose level to shorten overall treatment duration. This study presents the long-term results of adjuvant IMRT with SIB in elderly breast cancer patients who received partial mastectomy. Methods: From January 2007 to January 2018, 93 elder breast cancer patients (≥65-year-old) who received IMRT with SIB technique after partial mastectomy were reviewed retrospectively. The axillary areas were managed with either sentinel lymph node biopsies or axillary lymph node dissection. The dose to whole breast was 50.4 Gy in 28 fractions in all patients and the dose to tumor bed was 61.6 to 66.4 Gy in 28 fractions. The primary end point is locoregional control. Secondary end points include: overall survival, breast cancer-specific survival, distant-metastases-free survival, disease-free survival, and acute and chronic toxicities. Results: The median follow-up was 56.1 months. One patient had ipsilateral breast tumor recurrence, 3 patients had regional lymph node recurrence, and 9 patients had distant metastases. Death occurred in 5 patients, including 3 patients died of breast cancer progression. Five-year overall survival is 96.3% and 5-year locoregional recurrence-free survival is 96.4%. The 5-year breast cancer specific survival and 5-year distant metastases-free survival is 97.5% and 87.2%, respectively. Seven patients developed second primary cancer after RT. Eighty-one point seven percent patients had acute grade 1 dermatitis while 18.3% suffered from grade 2 dermatitis. The incidence of grade 1 pneumonitis and grade 1 stomatitis was 4.3% and 8.6%, respectively. Conclusions: Adjuvant IMRT with SIB technique is a safe and effective treatment strategy for elderly breast cancer patients after partial mastectomy.

Purpose: This study aimed to examine the relationships among trait resilience, coping styles, and perceived positive psychological changes in women's lives after breast cancer diagnosis and treatment.Design: The study adopted a cross-sectional design.Sample/Method: A total of 201 participants diagnosed with stage I-IV breast cancer were recruited. The average time since diagnosis was 39.14 months. Four rating scales were used to assess the participants' trait resilience, coping styles, perceived growth, and health-related quality of life. These are the Connor-Davidson Resilience Scale (CD-RISC), the Mini-Mental Adaptation to Cancer Scale (Mini-MAC), the Chinese Posttraumatic Growth Inventory (PTGI), and the Functional Assessment of Cancer Therapy Scale-Breast (FACT-B).Findings: Hierarchical analysis showed that trait resilience significantly predicted high levels of perceived growth and health-related quality of life. This effect was moderated by Positive-Acceptance coping. The study also found that Negative-Affect coping had a direct effect on lowering health-related quality of life but had no influence on perceived growth.Conclusions: These findings highlight the facilitating effect of trait resilience and Positive-Acceptance coping on the psychological well-being and perceived growth among breast cancer outpatients.Implications: Trait resilience may be a protective, even facilitating factor of cancer adaptation. The knowledge that trait resilience offers a way to enhance wellness after cancer diagnosis and treatments may be useful in a clinical setting.

Purpose Breast cancer (BC) is the most common cancer in women worldwide. There exist various advanced chemotherapy drugs for BC; however, chemotherapy drugs may result in brain damage during treatment. When a patient's brain is changed in response to chemo drugs, it is termed chemo-brain. In this study, we aimed to construct machine-learning models to detect the subtle alternations of the brain in postchemotherapy BC patients. Methods Nineteen BC patients undergoing chemotherapy and 20 healthy controls (HCs) were recruited for this study. Both groups underwent resting-state functional MRI and generalized q-sampling imaging (GQI). Results Logistic regression (LR) with GQI indices in standardized voxel-wise analysis, LR with mean regional homogeneity in regional summation analysis, decision tree classifier (CART) with generalized fractional anisotropy in voxel-wise analysis, and XGBoost (XGB) with normalized quantitative anisotropy had formidable performances in classifying subjects into a chemo-brain group or an HC group. Classifying the brain MRIs of HC and postchemotherapy patients by conducting leave-one-out cross-validation resulted in the highest accuracy of 84%, which was attained by LR, CART, and XGB with multiple feature sets. Conclusions In our study, we constructed the machine-learning models that were able to identify chemo-brains from normal brains. We are hopeful that these results will be helpful in clinically tracking chemo-brains in the future.

The prognosis of triple-negative breast cancer (TNBC) is worse and a major proportion of TNBC expresses epidermal growth factor receptor (EGFR). Afatinib can inhibit EGFR signal pathway; however, its treatment effect for TNBC is unknown. Thus, we aimed to assess the efficacy and biomarkers of afatinib in combination with paclitaxel in a neoadjuvant setting.Patients with stage II to III TNBC were enrolled. They received 40 mg of afatinib daily for 14 days, followed by daily afatinib and weekly paclitaxel (80 mg/mTwenty-one patients were enrolled and one patient achieved a complete clinical response; however, a 2 mm residual tumor was noted in the surgical specimen. Overall, 33.0% patients were responders. Fifteen patients received molecular testing. No activated mutation of EGFR or Her2 were found. Activated PI3K or JAK2 pathway were trended to associate with non-responder (p = 0.057). Mutation of homologous recombination (HR) genes were correlated with non-responsiveness (p = 0.005). Seven patients did not have altered PI3K, JAK2 or HR pathway; six (85.7%) of them were responder. Patients with the amplified DAXX gene was associated with a favorable trend of response (p = 0.109).Adding afatinib to neoadjuvant paclitaxel generated a modest effect in TNBC. Exploratory molecular analysis suggested that activated PI3K, JAK2 pathways and mutation of HR genes were associated with therapeutic non-responsiveness, and amplification of DAXX genes was associated with responsiveness to afatinib in combination with paclitaxel.

To apply deep learning algorithms using a conventional convolutional neural network (CNN) and a recurrent CNN to differentiate three breast cancer molecular subtypes on MRI. A total of 244 patients were analyzed, 99 in training dataset scanned at 1.5 T and 83 in testing-1 and 62 in testing-2 scanned at 3 T. Patients were classified into 3 subtypes based on hormonal receptor (HR) and HER2 receptor: (HR+/HER2−), HER2+, and triple negative (TN). Only images acquired in the DCE sequence were used in the analysis. The smallest bounding box covering tumor ROI was used as the input for deep learning to develop the model in the training dataset, by using a conventional CNN and the convolutional long short-term memory (CLSTM). Then, transfer learning was applied to re-tune the model using testing-1(2) and evaluated in testing-2(1). In the training dataset, the mean accuracy evaluated using tenfold cross-validation was higher by using CLSTM (0.91) than by using CNN (0.79). When the developed model was applied to the independent testing datasets, the accuracy was 0.4–0.5. With transfer learning by re-tuning parameters in testing-1, the mean accuracy reached 0.91 by CNN and 0.83 by CLSTM, and improved accuracy in testing-2 from 0.47 to 0.78 by CNN and from 0.39 to 0.74 by CLSTM. Overall, transfer learning could improve the classification accuracy by greater than 30%. The recurrent network using CLSTM could track changes in signal intensity during DCE acquisition, and achieved a higher accuracy compared with conventional CNN during training. For datasets acquired using different settings, transfer learning can be applied to re-tune the model and improve accuracy. • Deep learning can be applied to differentiate breast cancer molecular subtypes. • The recurrent neural network using CLSTM could track the change of signal intensity in DCE images, and achieved a higher accuracy compared with conventional CNN during training. • For datasets acquired using different scanners with different imaging protocols, transfer learning provided an efficient method to re-tune the classification model and improve accuracy.

Background The combination of lapatinib and oral vinorelbine for HER2 positive metastatic breast cancer (MBC) is convenient but with uncertain toxicity profiles. A Phase I/II study was designed to understand the tolerability and efficacy of this combination treatment. Method Female MBC patients with HER2 positive were eligible. Lapatinib was given once daily and oral vinorelbine was given on Days 1 and 8 of a 21-day cycle. A 3 + 3 standard dose-escalation rule was applied in the Phase I study. The primary endpoint of the Phase II study was PFS. In the Phase II part, because no DLT was observed in the first 20 patients, vinorelbine dose-escalation was permitted if no significant toxicities after the first cycle was observed. Result From June 2009 to February 2013, 46 patients were enrolled in Phase I (n = 15) and II (n = 31) studies. Median age was 52.8 (range 34.3-84.0); 28 (60.9%) patients were ER positive. In the Phase I study, two patients had DLTs (neutropenia (n = 2), diarrhea (n = 1)). The MTD was determined at lapatinib 1000 mg plus oral vinorelbine 50 mg/m2. In the Phase II study, 11 patients safely had vinorelbine escalated to 60 mg/m2 on cycle 2. The median PFS was 5.6 months (95% CI 5.2-5.9); 6 (19.4%) patients had PR; the clinical benefit rate was 38.7%. Six patients had disease control over 2 years. Conclusion Lapatinib 1000 mg and oral vinorelbine 50 mg/m2 were tolerable with manageable toxicities. Escalation to vinorelbine 60 mg/m2 is feasible if no significant toxicities after the first cycle. Clinical efficacy was demonstrated with long-term responders observed.

Jian-An Su,1–3,* Dah-Cherng Yeh,4,* Ching-Chi Chang,5,* Tzu-Chin Lin,6,7 Ching-Hsiang Lai,8 Pei-Yun Hu,8 Yi-Feng Ho,9 Vincent Chin-Hung Chen,1,2 Tsu-Nai Wang,10,11 Michael Gossop12 1Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 2Department of Medicine, School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Nursing, Chang Gung Institute of Technology, Taoyuan, Taiwan; 4Department of Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 5Institute of Medicine, Chung Shan Medical University and Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan; 7Department of Psychiatry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan; 9Tsaotun Psychiatric Center, Ministry of Health and Welfare, Nan-Tou,Taiwan; 10Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 12King’s College London, Institute of Psychiatry, London, UK *These authors contributed equally to this work Background: Breast cancer is the most common cancer in women. Among the survivors, depression is one of the most common psychiatric comorbidities. This paper reports the point prevalence of major depressive disorder among breast cancer patients and the association between family support and major depressive disorder.Methods: Clinical data were collected from a breast cancer clinic of a general hospital in central Taiwan. Participants included 300 patients who were older than 18 years and diagnosed with breast cancer. Among these individuals, we used Mini International Neuropsychiatric Interview (a structural diagnostic tool for psychiatric disorders) to ascertain if they had major depressive disorder. We also used the Family Adaptability, Partnership, Growth, Affection, and Resolve score to assess the family support.Results: The point prevalence of major depressive disorder among breast cancer patients was 8.33%, and this was positively associated with insomnia, psychiatric family history, pain severity, and radiotherapy and negatively associated with menopause, cancer duration, hormone therapy, and family support. Family support (adjusted odds ratio =0.87, 95% CI: 0.78–0.98) was found to be an associated factor for major depressive disorder in breast cancer patients after controlling for potential risk factors.Conclusion: Major depressive disorder is a common comorbidity among breast cancer patients. Family support is an important associated factor for these patients. Health care professionals should evaluate mood problems and family support while treating these patients. Keywords: breast cancer, prevalence, depression, family support, risk factors, psychiatric disorders

// Chia-Lin Lee 1, 2, 3, 4 , Chun-Hao Tsai 5, 6 , Dah-Cherng Yeh 7 , Chi-Shy Lin 8 , Yu-Fen Li 4 , Huey-En Tzeng 6, 9, 10 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan 2 Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan 3 Department of Medical Research, Taichung Veterans General Hospital, Taiwan 4 Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan 5 Department of Orthopedics, China Medical University Hospital, Taichung, Taiwan 6 School of Medicine, China Medical University, Taichung, Taiwan 7 Department of Surgery, Taichung Tzu Chi General Hospital, Taichung, Taiwan 8 Department of Family Medicine, Taichung Veterans General Hospital, Taiwan 9 Division of Hematology/Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 10 Breast Cancer Center, Taichung Veterans General Hospital, Taiwan Correspondence to: Yu-Fen Li, email: yufenli@mail.cmu.edu.tw Huey-En Tzeng, email: tzenghueyen@gmail.com Keywords: breast cancer, hemoglobin, survival, trajectory Received: October 06, 2016 Accepted: November 08, 2016 Published: November 29, 2016 ABSTRACT Hemoglobin (Hb) levels are reportedly related with treatment outcomes and survival in patients of breast cancer. However, the long-term change in Hb levels after treatment and the effects of Hb on survival remain unknown. This retrospective cohort study enrolled 1931 breast cancer patients with pathological stage I-IV between 1/1/2003 and 12/31/2013. Latent class modeling was used to identify trajectories in monthly Hb levels over time. The primary endpoint was 10-year cancer-related death. We identified 5 distinct Hb trajectories: persistent anemia (5.6 %; n = 109), improved anemia (4.8 %, n = 93), mild anemia (21.0%; n = 406), low normal Hb (46.6 %; n = 899), and normal Hb (21.9%; n = 424). Compared with the normal-Hb group, trajectories with low Hb levels had worst 10-year survival. The adjusted hazard ratios were 1.79(95% CI, 0.91-3.53) for the improved anemia group, 1.09(95% CI, 0.68-1.74) for the mild anemia group, 1.06 (95% CI, 0.71-1.60) for the low normal Hb group, and 2.19(95% CI 1.28-3.75) for the persistent anemia group. Our findings show there are five Hb level trajectories during breast cancer treatment. The anemia Hb level trajectory during the first 12 months after treatment reflect the worst cancer-related 10-year survival in breast cancer patients.

Background Breast neoplasms are the most common cancer among women in Taiwan. Cognitive deficits are common complications of breast cancer survivors treated with chemotherapy. The most frequently observed disorders involve executive function and memory impairment. With improvements in tumor intervention and the consequent increase in the number of cancer survivors, the quality of life of patients has become an important issue. We are interested in the early effects of chemotherapy on the brain structures of patients. In addition, generalized q-sampling imaging (GQI), a wide range of q-space datasets for a more accurate and sophisticated diffusion MR approach, was first used in this topic. Methods As diffusion tensor imaging (DTI) is associated with restrictions in the resolution of crossing fibers, we attempted to use GQI, which can overcome these difficulties and is advantageous over DTI for tractography of the crossing fibers. This cross-sectional study included two groups: breast cancer survivors who had completed their chemotherapy (n = 19) and healthy controls (n = 20). All participants underwent diffusion MRI exams and neuropsychological assessments. We included four parts in our image analysis, i.e., voxel-based statistical analysis, multiple regression analysis, graph theoretical analysis and network-based statistical analysis. Results The results from the voxel-based statistical analysis showed significantly lower GFA and NQA values in the breast cancer group than those in the control group. We found significant positive correlations between the FACT-Cog and GQI indices. In the graph theoretical analysis, the breast cancer group demonstrated significantly longer characteristic path length. Adjuvant chemotherapy affected the integrity of white matter and resulted in poor cognitive performance, as indicated by the correlations between the neuropsychological assessment scales and the GQI indices. In addition, it was found that the characteristic path lengths in the breast cancer group increased, indicating that the brain network integration became worse. Conclusions Our study demonstrated alterations in structural brain networks and associated neuropsychological deficits among breast cancer survivors.

Spiritual care is increasingly being recognized as an integral aspect of nursing practice. The aim of this study was to develop a new instrument, Spiritual Care Needs Inventory (SCNI), for measuring spiritual care needs in acute care hospital patients with different religious beliefs. The 21-item instrument was completed by 1,351 adult acute care patients recruited from a medical center in Taiwan. Principal components analysis of the SCNI revealed two components, (a) meaning and hope and (b) caring and respect, which together accounted for 66.2% of the total variance. The internal consistency measures for the two components were 0.96 and 0.91, respectively. Furthermore, younger age, female sex, Christian religion, and regularly attending religious activities had significantly higher mean total scores in both components. The SCNI was found to be a simple instrument with excellent internal consistency for measuring the spiritual care needs in acute care hospital patients.

Summary Background Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m 2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov, NCT01125566. Findings Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit–risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7–16·0). Median progression-free survival was 5·5 months (95% CI 5·4–5·6) in the afatinib group and 5·6 months (5·3–7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86–1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 [56%] of 337 patients in the afatinib group vs 102 [60%] of 169 patients in the trastuzumab group), leucopenia (64 [19%] vs 34 [20%]), and diarrhoea (60 [18%] vs none). Interpretation Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding Boehringer Ingelheim.

Objective To investigate the association between antidepressant prescription and breast cancer. Methods The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999–2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer. Results In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants. Conclusions There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

Background: Afatinib is an oral, irreversible ErbB family blocker with anti-tumour activity in patients (pts) with HER2-positive metastatic breast cancer (MBC) after failure on trastuzumab.1 Preclinically, afatinib + vinorelbine (AV) showed an additive effect; clinically, the AV combination had a manageable safety profile and showed activity in two Phase I trials.2,3 This randomized, open-label, Phase III trial (LUX-Breast 1) compared AV with trastuzumab + vinorelbine (TV) in pts with HER2-positive MBC who had progressed on a prior T-based regimen. Methods: Pts with HER2-positive MBC and failure of one T-based regimen (adjuvant/first-line) were randomized 2:1 to AV (40 mg/day oral + 25 mg/m2/week iv) or TV (2 mg/kg/week iv after 4 mg/kg loading dose + 25 mg/m2/week iv). Treatment continued until progressive disease (PD) or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS) by investigator review; secondary endpoints included objective response rate (ORR), overall survival (OS) and safety. Planned accrual was 780 pts. Results Between August 2010 and April 2013, 508 patients were randomized (AV:339, TV:169). Baseline characteristics were balanced in both arms (mean age 52 yrs, Asian 50.6%, White 41.6%, ER/PR positive 28.7%). 41.1% of pts failed on prior adjuvant and 58.9% on 1st line T-based treatment. A pre-planned risk/benefit assessment was found unfavorable by the DMC and recruitment was stopped. Pts ongoing on AV therapy were switched to TV, received A or V monotherapy, or stopped treatment. Primary endpoint analysis was performed with 307 of the originally 484 planned PFS events (211 [62.2%] AV arm; 96 [56.8%] TV arm). Median PFS was 5.5 months with AV vs 5.6 months with TV (HR 1.10; 95% CI 0.86, 1.41; P=0.4272). ORR was 46.1% with AV and 47.0% with TV (OR 1.04; 95% CI 0.71, 1.51; P=0.8510). OS analysis was based on 144 (28.4%) OS events (108 [31.9%] in AV arm; 36 [21.3%] in TV arm). Median OS was 19.6 months with AV and 28.6 months with TV (HR 1.76; 95% CI 1.20, 2.59; P=0.0036). The most common drug-related AEs were diarrhea (80.1%), neutropenia (75.1%) and rash (45.1%) with AV, and neutropenia (78.7%), leukopenia (37.3%) and anemia (27.8%) with TV. Rate of infections (53.0% vs 40.5%) was higher with AV vs TV. More AV than TV pts discontinued due to AEs (15.4% vs 7.1%). Fatal AEs were reported for 18 (5.3%) in the AV vs 5 (3.0%) pts in the TV arm, and were mainly associated with PD (9 pts in AV and 1 in TV arm). Three AV pts died due to treatment-related causes (sepsis/multi-organ failure; septic shock; pulmonary fibrosis). Conclusions: AV and TV demonstrated similar PFS and ORR, but OS diverged and was shorter for AV compared to TV in pts with HER2-positive MBC. The safety profile of AV was consistent with the individual monotherapies, but its tolerability compared unfavorably to TV. Analyses are ongoing to elucidate potential factors (e.g. impact of follow up treatments) contributing to the diverging PFS and OS outcomes. 1. Lin NU et al. Breast Cancer Res Treat 2012;133:1057-65 2. Bahleda R et al. J Clin Oncol 2011;29; abs 2585 3. Masuda N et al. SABCS 2013 abs P4-16-11. Citation Format: Nadia Harbeck, Chiun-Sheng Huang, Sara Hurvitz, Dah-Cherng Yeh, Zhimin Shao, Seock-Ah Im, Kyung Hae Jung, Kunwei Shen, Jungsil Ro, Jacek Jassem, Qingyuan Zhang, Young-Hyuck Im, Marek Wojtukiewicz, Qiang Sun, Shin-Cheh Chen, Rainer-Georg Goeldner, Annick Lahogue, Martina Uttenreuther-Fischer, Binghe Xu, Martine Piccart-Gebhart, on Behalf of the LUX-Breast 1 Study Group. Randomized Phase III trial of afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one prior trastuzumab treatment: LUX-Breast 1 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-01.

// Yu-Tang Tung 1, * , Pin-Wu Huang 1, * , Yu-Ching Chou 1 , Cheng-Wei Lai 1 , Hsiu-Po Wang 1 , Heng-Chien Ho 2 , Chih-Ching Yen 1, 3 , Chih-Yen Tu 1, 3 , Tung-Chou Tsai 1 , Dah-Cherng Yeh 4 , Jiun-Long Wang 1, 5 , Kowit-Yu Chong 6, 7 , Chuan-Mu Chen 1, 8 1 Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan 2 Department of Medicine, China Medical University Hospital, Taichung 404, Taiwan 3 Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan 4 Department of General Surgery and Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan 5 Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan 6 Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan 7 Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan 8 Rong-Hsing Translational Medicine Center and iEGG Center, National Chung Hsing University, Taichung 402, Taiwan * These authors have contributed equally to this work Correspondence to: Chuan-Mu Chen, e-mail: chchen1@dragon.nchu.edu.tw Keywords: VEGF, transgenic mice, pulmonary tumorigenesis, magnetic resonance imaging (MRI), miRNA therapy Received: November 03, 2014 Accepted: April 10, 2015 Published: April 22, 2015 ABSTRACT Many studies have shown that vascular endothelial growth factor (VEGF), especially the human VEGF-A 165 (hVEGF-A 165 ) isoform, is a key proangiogenic factor that is overexpressed in lung cancer. We generated transgenic mice that overexpresses hVEGF-A 165 in lung-specific Clara cells to investigate the development of pulmonary adenocarcinoma. In this study, three transgenic mouse strains were produced by pronuclear microinjection, and Southern blot analysis indicated similar patterns of the foreign gene within the genomes of the transgenic founder mice and their offspring. Accordingly, hVegf-A 165 mRNA was expressed specifically in the lung tissue of the transgenic mice. Histopathological examination of the lung tissues of the transgenic mice showed that hVEGF-A 165 overexpression induced bronchial inflammation, fibrosis, cysts, and adenoma. Pathological section and magnetic resonance imaging (MRI) analyses demonstrated a positive correlation between the development of pulmonary cancer and hVEGF expression levels, which were determined by immunohistochemistry, qRT-PCR, and western blot analyses. Gene expression profiling by cDNA microarray revealed a set of up-regulated genes ( hvegf-A 165 , cyclin b1 , cdc2 , egfr , mmp9 , nrp-1 , and kdr ) in VEGF tumors compared with wild-type lung tissues. In addition, overexpressing hVEGF-A 165 in Clara cells increases CD105, fibrogenic genes ( collagen α1 , α-SMA , TGF-β1 , and TIMP1 ), and inflammatory cytokines (IL-1, IL-6, and TNF- α ) in the lungs of hVEGF-A 165 -overexpressing transgenic mice as compared to wild-type mice. We further demonstrated that the intranasal administration of microRNA-16 (miR-16) inhibited lung tumor growth by suppressing VEGF expression via the intrinsic and extrinsic apoptotic pathways. In conclusion, hVEGF-A 165 transgenic mice exhibited complex alterations in gene expression and tumorigenesis and may be a relevant model for studying VEGF-targeted therapies in lung adenocarcinoma.

Purpose: We hypothesized that a window period between bevacizumab and cytotoxic agents may enhance drug delivery into tumor tissue through bevacizumab-induced vascular normalization in patients with brain metastases of breast cancer (BMBC). Experimental Design: A single-arm phase II study was conducted in which BMBC patients refractory to whole-brain radiotherapy (WBRT) were enrolled. In a 21-day cycle, patients received bevacizumab (15 mg/kg) on day 1, which, with a 1-day window period, was followed by etoposide (70 mg/m2/day; days 2–4) and cisplatin (70 mg/m2; day 2; BEEP regimen). The BEEP regimen was administered for a maximum of 6 cycles. The primary endpoint was the central nervous system (CNS)–objective response rate according to volumetric response criteria. Results: A total of 35 patients were enrolled between January 2011 and January 2013. The median age was 54.3 years (range, 33–75); 19 patients (54.3%) had an Eastern Cooperative Oncology Group performance status of 2 or 3. Twenty-seven patients [77.1%; 95% confidence interval (CI), 59.9–89.6] achieved a CNS-objective response, including 13 patients (37.1%) with a ≥80% volumetric reduction of CNS lesions. With a median follow-up of 16.1 months, the median CNS progression-free survival and overall survival times were 7.3 months (95% CI, 6.5–8.1) and 10.5 months (95% CI, 7.8–13.2), respectively. Common grade 3 or 4 toxicities included neutropenia (30.8%) and infection (21.3%). Conclusions: By administering bevacizumab 1 day before etoposide and cisplatin, the BEEP regimen appeared highly effective in BMBC refractory to WBRT. Further study of vascular normalization window concept is warranted. Clin Cancer Res; 21(8); 1851–8. ©2015 AACR.

Background and Objectives Unroofing hepatectomy, an alternative approach to remove a deep-seated hepatocellular carcinoma (HCC) adjacent to major intrahepatic vessels by peel-off technique after sacrificing the overlying noncancerous liver, may result in tumor exposure without resection margin. The aim of the study was to examine the value of this approach in cirrhotic patients. Methods Between 1998 and 2012, 51 cirrhotic patients underwent unroofing hepatectomy for deep-seated newly-diagnosed HCC adjacent to major intrahepatic vessels (group A). Another 274 cirrhotic patients with similar tumor size and without gross major vessel involvement in the same period were selected as the control cohort (group B). The patients' clinicopathological characteristics, the early and long-term outcomes of the two groups were compared. Results The HCCs in group A had a significantly higher rate of tumor encapsulation, smaller number of associated satellite nodules, and smaller amount of resected liver weight. Postoperative complication and 90-day mortality rates were similar, but group A patients had a significant better 5-year disease-free (56% vs. 32%, P = 0.011) and overall survival rates (82% vs. 53%, P = 0.008). Conclusions In selected cirrhotic patients, unroofing hepatectomy facilitates resection of deep-seated HCC adjacent to major intrahepatic vessels with acceptable early and long-term results. J. Surg. Oncol. 2015 111:396–403. © 2015 Wiley Periodicals, Inc.

To compare the dosimetric performance of 3 different treatment techniques: hybrid volumetric-modulated arc therapy (hybrid-VMAT), pure-VMAT, and fixed-field intensity-modulated radiation therapy (F-IMRT) for whole-breast irradiation of left-sided early breast cancer. The hybrid-VMAT treatment technique and 2 other treatment techniques—pure-VMAT and F-IMRT—were compared retrospectively in 10 patients with left-sided early breast cancer. The treatment plans of these patients were replanned using the same contours based on the original computed tomography (CT) data sets. Dosimetric parameters were calculated to evaluate plan quality. Total monitor units (MUs) and delivery time were also recorded and evaluated. The hybrid-VMAT plan generated the best results in dose coverage of the target and the dose uniformity inside the target (p < 0.0001 for conformal index [CI]; p = 0.0002 for homogeneity index [HI] of planning target volume [PTV](50.4 Gy) and p < 0.0001 for HI of PTV(62 Gy)). Volumes of ipsilateral lung irradiated to doses of 20 Gy (V(20 Gy)) and 5 Gy (V(5 Gy)) by the hybrid-VMAT plan were significantly less than those of the F-IMRT and the pure-VMAT plans. The volume of ipsilateral lung irradiated to a dose of 5 Gy was significantly less using the hybrid-VMAT plan than that using the F-IMRT or the pure-VMAT plan. The total mean MUs for the hybrid-VMAT plan were significantly less than those for the F-IMRT or the pure-VMAT plan. The mean machine delivery time was 3.23 ± 0.29 minutes for the hybrid-VMAT plans, which is longer than that for the pure-VMAT plans but shorter than that for the F-IMRT plans. The hybrid-VMAT plan is feasible for whole-breast irradiation of left-sided early breast cancer.

SummaryPhyllodes tumors (PTs) are an infrequent breast tumor presentation. An invasive carcinoma arising in a borderline PT is extremely rare. A 58-year-old female presented with a mass over the left breast, which she had had for >1 year, with rapid growth in the past 3 months. The patient underwent wide excision under the assumption that the mass was a PT. Invasive ductal carcinoma and ductal carcinoma in situ arising in a borderline PT were incidentally found. Because the surgical margin was

The normal breast tissue responds to the fluctuation of endogenous hormones during a menstrual cycle (MC) and shows changes in breast density. The changes between left and right breasts of the same women were compared to evaluate the symmetrical response. Twenty-four healthy women were recruited in this study. Four weekly magnetic resonance imaging (MRI) studies were performed during one MC. A computer algorithm was used to segment the breast and the fibroglandular tissue to measure the fibroglandular tissue volume (FV) and three morphological parameters: circularity, convexity and irregularity. The coefficient of variation (CV) for each parameter measured among four MRI studies was calculated; also, the maximal percent change between two MRI studies that show the highest and the lowest FV was calculated. These parameters measured from left and right breasts were compared using Pearson correlation. For the FV, the CV measured between left and right breasts of 24 subjects was highly correlated, with r=0.91; the maximal percent difference was also highly correlated, with r=0.93. Overall, the mean left-to-right difference in the measured FV was small: 1.2%±1.1% for CV and 2.6%±2.3% for the maximal percent difference. For the three morphological parameters, the mean left-to-right percentage difference was similar to the differences seen in FV; however, these morphological parameters do not reveal a high functional symmetry between left and right breasts. The results showed that the measured FV from left and right breasts of the same woman revealed a high functional symmetry. Since endogenous hormone plays an important role in the development of breast cancer, it would be interesting to investigate whether the functional asymmetry of response in some patients is associated with the risk of developing unilateral breast cancer.

Background: Spirituality is a necessary component of life. Spiritual care includes the activities necessary to meet the spiritual needs of clients. Nursing students must receive appropriate training to develop their abilities to provide spiritual care.Purpose: This study explored student nurse perceptions of spirituality and spiritual care and related factors.Methods: We used a cross-sectional descriptive design and purposive sampling. Participants were senior nursing students of both genders from 22 schools. The Chinese version of a spirituality and spiritual scale was the research tool. A total of 239 participants returned the questionnaires, giving a response rate of 91.92%.Results: Average participant age was 19.48 years; 45.61% reported no religion; 65.59% did not participate in religious activities; 94.56%reported having an interest in nursing; 52.72% were undecided about pursuing a nursing career; 3.35%did not want to be nurses; 46.44% had taken spirituality courses in school; 53.56% had taken spiritual care courses. Participants' overall perception of spirituality and spiritual care was ”clear.” This runs contrary to the idea that only religious people are spiritual and that nonreligious nurses may be less able to tend to the spiritual needs of their patients. Participants who had taken spirituality or spiritual care courses had an interest in nursing and were willing to become nurses had, on average, significantly better spirituality knowledge and spiritual care attitudes than other participants.Conclusions/Implications for Practice: This study found that education, experience, career interest in nursing, and career choice affects nursing student perceptions of spirituality and spiritual care. We also found that this effect was independent of gender. Nursing students should be holistic care providers. Integrating spirituality and spiritual care into the standard nursing curriculum is recommended to improve nursing care quality.

Purpose: To compare the breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from breast MRI of the same women using four different MR scanners. Methods: The study was performed in 34 healthy Asian volunteers using two 1.5T (GE and Siemens) and two 3T (GE and Philips) MR scanners. The BV, FV, and PD were measured on nonfat-suppressed T1-weighted images using a comprehensive computer algorithm-based segmentation method. The scanner-to-scanner measurement difference, and the coefficient of variation (CV) among the four scanners were calculated. The measurement variation between two density morphological patterns presenting as the central type and the intermingled type was separately analyzed and compared. Results: All four scanners provided satisfactory image quality allowing for successful completion of the segmentation processes. The measured parameters between each pair of MR scanners were highly correlated, with R2 ≥ 0.95 for BV, R2 ≥ 0.99 for FV, and R2 ≥ 0.97 for PD in all comparisons. The mean percent differences between each pair of scanners were 5.9%–7.8% for BV, 5.3%–6.5% for FV, 4.3%–7.3% for PD; with the overall CV of 5.8% for BV, 4.8% for FV, and 4.9% for PD. The variation of FV was smaller in the central type than in the intermingled type (p = 0.04). Conclusions: The results showed that the variation of FV and PD measured from four different MR scanners is around 5%, suggesting the parameters measured using different scanners can be used for a combined analysis in a multicenter study.

Objective The aim of this study is twofold. First, it aims to determine the factor structure of the Mini-Mental Adjustment to Cancer (Mini-MAC) Scale by using confirmatory factor analysis (CFA) to compare the three-factor, four-factor, and five-factor structures among 340 Taiwanese breast cancer patients. Second, it aims to test the difference in the correlations of coping strategies and the outcome measures between two populations: one-month newly diagnosed and five-year long-term survival patients. Methods Two samples, composed of 142 newly diagnosed and 198 long-term survival breast cancer patients, were recruited. Cancer-specific coping and distress were assessed via the Mini-MAC Scale and the Hospital Anxiety and Depression Scale (HADS), respectively. Results The CFA confirmed Watson's original five-factor structure fit the data best. The correlation difference between the two samples lies in the fighting spirit (FS), which correlated negatively with distress among the newly diagnosed sample but had no correlation among the long-term survivors. Moreover, fatalism (FA) was found to correlate positively with distress. Conclusions The five-factor structure represents a more psychometrically sound measure of psychological adjustment in the current data set. The findings also support the argument that the relationships between coping and distress vary, to some degree, at different phases in the cancer trajectory. FS is only a positive predictor of psychological adjustment among newly diagnosed patients. Because of the exclusion of two items, FA showed a positive correlation with distress, a result that contradicts previous findings. Further theoretical and practical implications for FS and FA are discussed.Copyright © 2012 John Wiley & Sons, Ltd.

The necessity of hepatic vein reconstruction (HVR) after resection of cranial part of the liver and major hepatic vein(s) in cirrhotic patients when residual liver is insufficient for a major hepatectomy remains unclear.Fifty-two cirrhotic patients who underwent resection of cranial part of the liver and hepatic vein(s) for liver neoplasms were divided retrospectively into 3 groups based on the volume of the congestive area of the remnant liver after hepatectomy: group A, 28 patients, the volume of the congestive area was ≤20% of the residual liver volume and underwent no HVR; group B, 7 patients, the volume of the congestive area was20% of residual liver volume and underwent no HVR; and group C, 17 patients, in whom HVR was performed (the volume of the congestive area was20% of residual liver volume in 16 and20% in 1). Background characteristics and postoperative results were compared between the groups.Although group C patients had a significantly longer operative time, their postoperative courses were similar to group A patients. Group B patients had a significantly longer postoperative hospital stay and a greater postoperative morbidity and 90-day mortality. No 90-day mortality ensued in the group A and C patients.In selected cirrhotic patients whose remnant liver is insufficient for major hepatectomy, HVR appears to be safe and desirable after resection of the cranial part of liver and hepatic vein when the volume of congestive area of liver remnant exceeds 20% of future residual liver volume.

Background Liver resection is the main curative treatment for hepatocellular carcinoma (HCC), but recurrence rates are high. The remnant liver is the most common site of recurrence, but the role of repeat hepatectomy in the treatment of recurrent HCC is controversial. Methods Patients who underwent curative hepatectomy for HCC and subsequent repeat hepatectomy for recurrent HCC between 1990 and 2007 were reviewed retrospectively. Clinicopathological characteristics, and early- and long-term outcomes of patients who had a first, second, third and fourth hepatectomy were compared. Results Some 1177 patients underwent a first hepatectomy for HCC, and 149, 35 and eight patients respectively had a second, third and fourth hepatectomies for recurrence. There were no significant differences in early postoperative outcomes after first and repeat hepatectomies. Five-year disease-free and overall survival rates after first, second and third hepatectomies were 43·6, 31·8 and 33·8 per cent (P = 0·772), and 52·4, 56·4 and 59·4 per cent (P = 0·879), respectively. Patients undergoing second and third hepatectomies for recurrence had better survival rates than those who did not have a repeat hepatectomy, but not those after fourth hepatectomy. Conclusion Second and third hepatectomies seem justified for hepatic recurrence of HCC. The role of fourth hepatectomy needs further investigation.

In this study, a semi-automatic breast segmentation method was proposed on the basis of the rib shadow to extract breast regions from 3-D automated whole-breast ultrasound (ABUS) images. The density results were correlated with breast density values acquired with 3-D magnetic resonance imaging (MRI). MRI images of 46 breasts were collected from 23 women without a history of breast disease. Each subject also underwent ABUS. We used Otsu's thresholding method on ABUS images to obtain local rib shadow information, which was combined with the global rib shadow information (extracted from all slice projections) and integrated with the anatomy's breast tissue structure to determine the chest wall line. The fuzzy C-means classifier was used to extract the fibroglandular tissues from the acquired images. Whole-breast volume (WBV) and breast percentage density (BPD) were calculated in both modalities. Linear regression was used to compute the correlation of density results between the two modalities. The consistency of density measurement was also analyzed on the basis of intra- and inter-operator variation. There was a high correlation of density results between MRI and ABUS (R(2) = 0.798 for WBV, R(2) = 0.825 for PBD). The mean WBV from ABUS images was slightly smaller than the mean WBV from MR images (MRI: 342.24 ± 128.08 cm(3), ABUS: 325.47 ± 136.16 cm(3), p < 0.05). In addition, the BPD calculated from MR images was smaller than the BPD from ABUS images (MRI: 24.71 ± 15.16%, ABUS: 28.90 ± 17.73%, p < 0.05). The intra-operator and inter-operator variant analysis results indicated that there was no statistically significant difference in breast density measurement variation between the two modalities. Our results revealed a high correlation in WBV and BPD between MRI and ABUS. Our study suggests that ABUS provides breast density information useful in the assessment of breast health.

To investigate the association between antidepressant prescription and breast cancer.The National Health Research Institute in Taiwan provided a database of 1 000 000 random subjects for this study. We identified 14 737 new antidepressant female users who were more than 15 years old during 1999-2005 with at least 10 prescriptions and one year exposure to an antidepressant. These were matched 1:1 by age and residence to non-antidepressant users from the same database to compare the risk of breast cancer.In a model adjusted by age, residence, insurance amount, and depressive disorder, antidepressant prescription was not associated with breast cancer risk. This held true for both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants.There was no evidence for an association between antidepressant prescription and the risk of breast cancer. Copyright © 2015 John WileySons, Ltd.

Large cell neuroendocrine carcinoma in the ampulla of Vater is rare and very different from the common ampullary adenocarcinoma. A 59-year-old man was admitted with obstructive jaundice. Gastroendoscopy showed a swollen ampulla of Vater and pathological examination of an ampullary biopsy revealed findings of a carcinoid tumor. After endoscopic biliary drainage, he underwent pancreaticoduodenectomy. A diagnosis of large cell neuroendocrine carcinoma was confirmed by immunohistochemical examination of the resected specimen. Despite adjuvant chemotherapy with cyclophosphamide and cisplatin, liver and peritoneal metastasis developed within 5 months and he survived for only 10 months after the operation. Thus, further investigations are needed to find a more effective postoperative adjuvant chemotherapy agent to treat patients with this aggressive tumor.

Glucocorticoid receptor (GR) was first found in the cytosol of gastric cancer tissue more than 15 years ago. At present, most gastric cancers are diagnosed at the advanced stage. To elucidate the role of GR in gastric cancer, the GR levels of the cancer tissue of 75 consecutive patients with grossly serosa-involved gastric carcinoma were determined by the dextran-coated charcoal method. The clinicopathologic characteristics and long-term survival duration were compared in patients with GR-positive and GR-negative cancer cells. We found that GR could be detected in the cytosol of cancer cells in 31 (41.3%) of the gastric cancer patients with a median concentration of 18.5 (range, 1.03-73.9) fmol/mg protein. No significant differences could be found in any clinicopathologic characteristic between the patients with GR-positive and GR-negative cancers. After multivariate analysis, gross Borrmann's type, metastatic lymph node number, and GR positivity were the independent prognostic factors after gastrectomy for serosa-involved gastric carcinoma. GR-positive gastric cancer had a worse survival rate than GR-negative gastric cancer. Multimodality adjuvant therapies should be considered in patients with GR-positive serosa-involved gastric carcinoma.

Liver resection remains a main option for primary or metastatic liver malignancies, benign liver tumors, and some biliary diseases.1–20 However, liver resection is still a complex procedure and should be performed in high-volume centers.21 With advances in perioperative assessments and surgical equipment, the safety of liver resection improved.2,4,5,13 A total of 1056 consecutive liver resections without operative mortality has even been reported recently.5 It is well known that a hyperfibrinolytic state may occur after liver resection or liver trauma.22–24 Hemorrhage is still a major problem in liver resection at present.2–24 Homologous blood transfusion is inevitable if blood loss threatens vital signs.2,3,15 However, blood transfusion may transmit some infectious diseases, increase postoperative morbidity and mortality, and cause a poor prognosis of primary and secondary liver malignancies.4–13,20 A bloodless hepatectomy to avoid blood transfusion was first considered a realistic objective in the late 1980s.3,9,10 Many strategies or operative devices were proposed to approach the goal of a “blood transfusion”-free hepatectomy.2–20 With these new devices and strategies, the amount of operative bleeding markedly reduced, and the rate of blood transfusion in liver resection was substantially reduced.1,2,4–8,11–13,20 Donor hepatectomy in living donor liver transplantation is usually performed without blood transfusion.1,4,5,25 The liver parenchyma of the living donors is unexceptionally normal.4,5,25 In recent reports, a total “blood transfusion”-free liver resection was performed.11,12,20 However, patient numbers in these reports11,12,20 were limited, and the liver parenchyma of the majority of the patients was rarely abnormal. Tranexamic acid (TA), 4-aminomethyl-cyclohexanecarboxylic acid, a synthetic derivative of the amino-acid lysine, has been reported to reduce bleeding in many surgical procedures, such as arthroplasty, cardioaortic surgery under cardiopulmonary bypass, and in liver transplantation by its antifibrinolytic effect.26–32 TA prevents the plasmin-mediated conversion of fibrinogen to fibrinogen split products by inhibition of the lysine-binding sites on plasminogen molecules, thus blocking fibrinolysis.26–29 It also inhibits plasminogen and plasmin at platelets and exerts a protective effect on platelets.26–32 Another antifibrinolytic agent, aprotinin, a nonspecific serine protease inhibitor derived from bovine lung with a great affinity for plasmin and low affinity for kallikrein, can reduce platelet dysfunction, thereby inhibiting fibrinolysis.24,28,29 Aprotinin has been reported, effective reducing blood transfusion in the aforementioned surgical procedures.24,28,29 It is also effective in reducing operative blood loss and blood transfusion after liver resection.24 TA is much cheaper than aprotinin,28,29 but its antifibrinolytic effect in liver resection has never been reported. As a tertiary referral center in an endemic area of hepatitis B, we frequently resected liver tumor in diseased livers.13–15,33 In this study, a prospective double-blind, randomized trial of perioperative parenteral TA in liver resection was carried out to evaluate the influence of blood transfusion of this drug on liver resection. The feasibility of “blood transfusion”-free hepatectomy in a large group of patients was also examined.

Background and Objectives Because renal transplantation recipients require immunosuppressive drugs, they have a higher incidence of subsequent malignancies. Among them, hepatocellular carcinoma (HCC) is common. Although liver resection remains an option for curing HCC, the role of liver resection in renal transplantation recipients remains unclear. Methods A retrospective review of liver resection for newly diagnosed HCC in 680 patients was conducted. Among them, 18 patients had undergone prior renal transplantation (RT group). The patient background, tumor characteristics, early and long-term results after liver resection were compared with the other 662 patients who had not previously undergone renal transplantation (non-RT group). Results The patient's background characteristics were comparable between RT and non-RT group. The tumor characteristics, postoperative morbidity, and mortality were not significantly different between the two groups. The 5-year disease-free survival rates in RT and non-RT groups were 18.8% and 41.2%, respectively (P = 0.242), whereas 5-year actuarial survival rates in RT and non-RT groups were 59.1% and 58.3%, respectively (P = 0.738). Two patients lost their graft kidney 3 and 8 years after liver resection. Conclusion With careful protection of the graft kidney, liver resection is still a justified treatment option for HCC in patients who have undergone renal transplantation. J. Surg. Oncol. 2006;93: 273–278. © 2006 Wiley-Liss, Inc.

We assessed the effect of zoledronic acid on quality of life (QOL) and pain outcome in breast cancer patients with bone metastases using the European Organization for Research and Treatment of Cancer bone metastases module (EORTC QLQ-BM22).Three hundred sixty-six breast cancer patients receiving zoledronic acid for bone metastases from 13 Centers were prospectively enrolled. QOL was evaluated using the EORTC QLQ-BM22 and pain outcome were measured monthly with a Visual Analog Scale (VAS) score for 24 months.No significant change of functional scale (functional interference and psychosocial aspects) of the EORTC QLQ-BM22 was reported. Significant reduction of the symptom scale was noted after treatment compared with the baseline. The painful site subscale was significantly reduced during the first 12 months, with the exception the 6-month follow-up of point. Pain characteristics subscale was also significantly lower from the 2-month time point onwards. VAS scores indicated a significant reduction in pain over the course of the study to the 22-month time point follow-up compared to the baseline.Zoledronic acid treatment improved QOL of breast cancer patients with bone metastases by relieving bone pain.

Background Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer. Methods Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed. Results Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3–9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0–10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF. Conclusions BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease. Trial registration ClinicalTrials.gov identifying number NCT01281696. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1290-1) contains supplementary material, which is available to authorized users.

Unroofing hepatectomy, an alternative approach to remove a deep-seated hepatocellular carcinoma (HCC) adjacent to major intrahepatic vessels by peel-off technique after sacrificing the overlying noncancerous liver, may result in tumor exposure without resection margin. The aim of the study was to examine the value of this approach in cirrhotic patients.Between 1998 and 2012, 51 cirrhotic patients underwent unroofing hepatectomy for deep-seated newly-diagnosed HCC adjacent to major intrahepatic vessels (group A). Another 274 cirrhotic patients with similar tumor size and without gross major vessel involvement in the same period were selected as the control cohort (group B). The patients' clinicopathological characteristics, the early and long-term outcomes of the two groups were compared.The HCCs in group A had a significantly higher rate of tumor encapsulation, smaller number of associated satellite nodules, and smaller amount of resected liver weight. Postoperative complication and 90-day mortality rates were similar, but group A patients had a significant better 5-year disease-free (56% vs. 32%, P = 0.011) and overall survival rates (82% vs. 53%, P = 0.008).In selected cirrhotic patients, unroofing hepatectomy facilitates resection of deep-seated HCC adjacent to major intrahepatic vessels with acceptable early and long-term results.

Background Liver resection in a patient with cirrhosis carries increased risk. The purposes of this study were to review the results of cirrhotic liver resection in the past decade and to propose safe strategies for cirrhotic liver resection. Methods Based on the date of operation, 359 cirrhotic liver resections in 329 patients were divided into two intervals: period 1, from September 1989 to December 1994, and period 2, from January 1995 to December 1999. The patient backgrounds, operative procedures and early postoperative results were compared between the two periods. The factors that influenced surgical morbidity were analysed. Results In period 2, patient age was higher and the amounts of blood loss and blood transfused were lower. Although postoperative morbidity rates were similar, blood transfusion requirement, postoperative hospital stay and mortality rate were significantly reduced in period 2. No death occurred in 154 consecutive cirrhotic liver resections in the last 38 months of the study. Prothrombin activity and operative time were independent factors that influenced postoperative morbidity. Conclusion With improving perioperative assessment and operative techniques, most complications after cirrhotic liver resection can be treated with a low mortality rate. However, more care should be taken if prothrombin activity is low or there is a long operating time.

The current study aimed to examine the impact of zoledronic acid therapy on health-related quality of life (HRQoL) in Taiwanese patients with bone metastases from breast cancer.Patients with bone metastases from breast cancer who received zoledronic acid according to the standards of care were enrolled in this observational phase IV study. HRQoL was measured monthly using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (QLQ-C30) and the breast cancer-specific module (BR-23) for 24 months.A total of 366 patients from 13 centers were enrolled. QLQ C-30 demonstrated that zoledronic acid improved the HRQoL in different aspects. In particular, a significant reduction of pain in the first 14 months and the 22-month follow-up was reported by patients. QLQ-BR23 indicated improved future perspective and breast symptom scores over the course of the study.These data confirm the HRQoL benefits and safety of zoledronic acid in Taiwanese patients with bone metastases from breast cancer.

The surgery for breast cancer consists of axillary lymphadenectomy and total or partial mastectomy for achieving maximal local control of the cancer and precise staging. Lymphatic spreading of breast cancer is the exclusive reason to perform axillary lymphadenectomy. Previous data 1,18,21 showed that the incidence of axillary lymph node (ALN) metastasis was proportional to the tumor size, that is, the bigger the tumor, the greater the chance of ALN metastasis resulting. A 15% to 20% ALN metastatic rate, however, was noted in patients with a 1-cm primary tumor. From another viewpoint, nearly 80% of this kind of patient had axillary nodes with no cancer, and lymphadenectomy was absolutely unnecessary, and therefore, related complications could be avoided. 4 Twenty percent to 30% of patients with a tumor 5cm in diameter still had a disease-free axilla. 1,21 % Axillary dissection was not necessary for those patients, as well. To solve this problem, Cabanas proposed the sentinel lymph node concept based on the lymphatic drainage theory. 5 The first lymph node, sentinel lymph node (SLN), exposed to lymphatic fluid from a primary lesion has the highest chance of cancer metastasis, and the remaining lymph nodes will have subsequent metastasis. If the SLN is free of cancer, the remaining lymph nodes will not have cancer either. Therefore, using this method to select a breast cancer patient for axillary dissection is quite hopeful. Current clinical application of this concept demonstrates very encouraging results in breast cancer. 2,11,12,14,17,22 In the past, the incidence of breast cancer in the Chinese had not been as high as that in Europeans and Americans. 6 The incidence of occurrence, however, has increased fivefold, and the mortality rate has increased threefold in the last two decades. 9 The diagnosis of early breast cancer (stages I and II) has risen from 40% in 1980 to 60% in late 1990. More breast cancer patients have presented with impalpable axillary lymph nodes since the screening of breast cancer was begun. Whether axillary lymphadenectomy is necessary for this increased number of patients urgently needs to be studied.

Background: The role of surgical resection for hepatocellular carcinoma with tumor thrombi involving the major portal vein is controversial because of a high operative risk and poor prognosis. Previously, a resection was performed only when the tumor thrombi were limited to the first branch of the portal vein without extension to the portal bifurcation. Hypothesis: Concomitant liver and portal vein resection may be beneficial in patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation. Design: Retrospective review. Setting: University hospital, tertiary referral center. Patients: Among 368 patients with hepatocellular carcinoma who underwent a curative resection, portal vein involvement occurred in 112 patients. Fifteen of the 112 patients underwent a concomitant liver and portal vein resection owing to extension of tumor thrombi to the portal bifurcation (group 1). The remaining 97 patients did not need portal vein resection (group 2). Intervention: Surgical indications, procedures, and results of pathological examination of resected specimens were assessed in patients in group 1. The clinicopathological characteristics, operative morbidity and mortality, and operative results were compared between the 2 groups. Main Outcome Measures: Disease-free and actuarial survival rates. Results: Intramural tumor infiltration was found at the site of thrombi adhesion to the portal vein cuff in 11 of 15 patients in group 1. Owing to patient selection bias, patients in group 1 were significantly younger and had better liver function and greater resected liver weight. The operative time, postoperative hospitalization, operative blood loss, amount of blood transfusion, and operative morbidity and mortality did not differ significantly between the 2 groups. The 5-year disease-free survival rates of groups 1 and 2 were 21.6% and 20.4% (P=.19), respectively, while the actuarial survival rates were 26.4% and 28.5% (P=.33), respectively. Conclusion: Liver resection with partial resection of the portal vein is justified in selected patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.