The Attitudes of Physicians and the General Public toward Prognostic Disclosure of Different Serious Illnesses: a Korean Nationwide Study.

BACKGROUND: Although international guidelines recommend palliative care approaches for many serious illnesses, the palliative needs of patients with serious illnesses other than cancer are often unmet, mainly due to insufficient prognosis-related discussion. We investigated physicians' and the general public's respective attitudes toward prognostic disclosure for several serious illnesses. METHODS: We conducted a cross-sectional survey of 928 physicians, sourced from 12 hospitals and the Korean Medical Association, and 1,005 members of the general public, sourced from all 17 administrative divisions in Korea. RESULTS: For most illnesses, most physicians (adjusted proportions - end-organ failure, 99.0%; incurable genetic or neurologic disease, 98.5%; acquired immune deficiency syndrome [AIDS], 98.4%; stroke or Parkinson's disease, 96.0%; and dementia, 89.6%) and members of the general public (end-organ failure, 92.0%; incurable genetic or neurologic disease, 92.5%; AIDS, 91.5%; stroke or Parkinson's disease, 92.1%; and dementia, 86.9%) wanted to be informed if they had a terminal prognosis. For physicians and the general public, the primary factor to consider when disclosing terminal status was "the patient's right to know his/her condition" (31.0%). Yet, the general public was less likely to prefer prognostic disclosure than physicians. Particularly, when their family members were patients, more than 10% of the general public did not want patients to be informed of their terminal prognosis. For the general public, the main reason for not disclosing prognosis was "psychological burden such as anxiety and depression" (35.8%), while for the physicians it was "disclosure would have no beneficial effect" (42.4%). CONCLUSION: Most Physicians and the general public agreed that disclosure of a terminal prognosis respects patient autonomy for several serious illnesses. The low response rate of physicians might limit the generalizability of the results.

Correction to: Priorities of a "good death" according to cancer patients, their family caregivers, physicians, and the general population: a nationwide survey.

While recently extending that research, however, we discovered that 236 members of the general population were mistakenly duplicated by the investigating agency (Word Research) and 1241 were reported rather than 1005. Here, we present corrections and discuss the relevant data.

Priorities of a "good death" according to cancer patients, their family caregivers, physicians, and the general population: a nationwide survey.

PURPOSE: Understanding the concept of a "good death" is crucial to end-of-life care, but our current understanding of what constitutes a good death is insufficient. Here, we investigated the components of a good death that are important to the general population, cancer patients, their families, and physicians. METHODS: We conducted a stratified nationwide cross-sectional survey of cancer patients and their families from 12 hospitals, physicians from 12 hospitals and the Korean Medical Association, and the general population, investigating their attitudes toward 10 good-death components. FINDINGS: Three components-"not be a burden to the family," "presence of family," and "resolve unfinished business"-were considered the most important components by more than 2/3 of each of the three groups, and an additional three components-"freedom from pain," "feel that life was meaningful," and "at peace with God"-were considered important by all but the physicians group. Physicians considered "feel life was meaningful," "presence of family," and "not be a burden to family" as the core components of a good death, with "freedom from pain" as an additional component. "Treatment choices' followed, "finances in order," "mentally aware," and "die at home" were found to be the least important components among all four groups. CONCLUSION: While families strongly agreed that "presence of family" and "not be a burden to family" were important to a good death, the importance of other factors differed between the groups. Health care providers should attempt to discern each patient's view of a good death.

Exogenous Hydrogen Peroxide Induces Lipid Raft-Mediated STAT-6 Activation in T Cells.

BACKGROUND/AIMS: CD4+ T cells are a critical component of the adaptive immune response. While the mechanisms controlling the differentiation of the Th1, Th17, and regulatory T cell subsets from naïve CD4+ T cells are well described, the factors that induce Th2 differentiation are still largely unknown. METHODS: The effects of treatment with exogenous H2O2 on STAT-6 phosphorylation and activation in T cells were examined by immunoblotting, immunofluorescence and gel shift assay. Anti-CD3 antibody and methyl-ß-cyclodextrin were utilized to induce lipid raft assembly and to investigate the involvement of lipid rafts, respectively. RESULTS: Jurkat and EL-4 T cells that were exposed to H2O2 showed rapid and strong STAT-6 phosphorylation, and the extent of STAT-6 phosphorylation was enhanced by co-treatment with anti-CD3 antibody. The effect of H2O2 on STAT-6 phosphorylation and translocation was inhibited by disruption of lipid rafts. STAT-6 activation in response to H2O2 treatment regulated IL-4 gene expression, and this response was strengthened by treatment with anti-CD3. CONCLUSION: Our results indicate that reactive oxygen species such as H2O2 can act on upstream and initiating factors for activation of STAT-6 in T cells and contribute to formation of a positive feedback loop between STAT-6 and IL-4 in the Th2 differentiation process.

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors.

BACKGROUND: We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. METHODS: We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). RESULTS: For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. CONCLUSION: Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. TRIAL REGISTRATION: Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012).

Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06).

BACKGROUND: KIT has been suggested to be a potential therapeutic target for malignant melanoma. We evaluated the antitumor activity and safety of the KIT inhibitor nilotinib in metastatic melanoma patients harboring KIT gene mutations or amplifications. METHODS: We conducted a phase II multicenter trial of nilotinib in metastatic malignant melanoma with KIT mutations or amplifications. Patients received 400 mg oral nilotinib twice daily. The primary endpoint was response rate, and if seven or more responders were observed from the cumulative 36 patients, nilotinib would be considered worthy of further testing in this study population. RESULTS: Between October 2009 and June 2013, 176 patients underwent molecular screening for KIT gene aberrations, and 42 patients harboring KIT gene mutations and/or amplification were enrolled in the study. Overall, 25 (59.5%), 15 (35.7%), and 2 (4.8%) patients had KIT mutations, KIT amplifications, and both KIT mutations and amplification, respectively. Of the 42 enrolled patients, 1 patient achieved complete response, 6 patients achieved partial response, and 17 patients achieved stable disease, resulting in an overall response rate of 16.7% (95% confidence interval [CI]: 5.4%-28.0%) and a disease control rate of 57.1% (95% CI: 42.1%-72.1%). The median duration of response was 34 weeks (range: 5-55 weeks). Of the 7 responders, 6 patients had KIT mutations (exon 11: 5 patients; exon 17: 1 patient), and 1 patient had KIT amplification only. CONCLUSION: Although this study did not meet its primary endpoint of response rate, nilotinib showed durable response in a subset of metastatic melanoma patients with specific KIT mutations. IMPLICATIONS FOR PRACTICE: KIT aberration can be detected in a subset of metastatic melanoma patients. This phase II trial showed that nilotinib demonstrates durable response in a subset of patients with KIT mutations. The safety profile was very tolerable. This study suggests that a KIT inhibitor may benefit a small subset of metastatic melanoma patients with KIT mutations.

Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21.

BACKGROUND: A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. METHODS: Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%. RESULTS: A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. CONCLUSION: RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

The association of self-leadership, health behaviors, and posttraumatic growth with health-related quality of life in patients with cancer.

PURPOSE: We tried to evaluate the association of self-leadership, effective health behaviors, and posttraumatic growth with health-related quality of life (HRQOL). METHODS: We recruited survivors of cancer from seven hospitals in Korea between 2011 and 2012. The patients completed the Seven Habits Profile (7HP) to evaluate leadership competency, the 10 rules for highly effective health behavior to evaluate health behavior, the Posttraumatic Growth Inventory (PTGI) to evaluate posttraumatic growth, the Short Form 36 (SF-36) to evaluate HRQOL, and the Hospital Anxiety and Depression Scale (HADS) to evaluate anxiety and depression. We performed multiple logistic regressions to identify significant associations. RESULTS: A total of 668 patients with cancer participated in the study. Patients who scored high on the leadership subscales of Be Proactive, Begin with the End in Mind, Put First Things First, Think Win-Win, Synergize, and Sharpen the Saw in 7HP tried to practice and keep their health behaviors more. The Begin with the End in Mind, Put First Things First, Synergize, and Sharpen the Saw subscales of the 7HP were also significantly correlated with subscales on the PTGI. Patients who scored high on the leadership subscales of Life Balance, Be Proactive, Begin with the End in Mind, Think Win-Win, and Sharpen the Saw had higher physical and mental component scale scores on the SF-36 and lower anxiety and depression subscale scores on the HADS. CONCLUSION: Self-leadership, health behaviors, and posttraumatic growth are associated with QOL in survivors of cancer.

The attitudes of Korean cancer patients, family caregivers, oncologists, and members of the general public toward advance directives.

PURPOSE: The purpose of this study was to investigate Korean attitudes toward advance directives (ADs) among cancer patients, family caregivers, oncologists, and the general public. METHODS: A multicenter survey study explored the attitudes of participants to ADs, and hospice-palliative care (HPC) was conducted. A total of 1,242 cancer patients, 1,289 family caregivers, 303 oncologists, and 1,006 members of the general public participated in the survey. RESULTS: The majority of patients, family caregivers, oncologists, and general public agreed with the necessity of ADs. However, oncologists regard "when became terminal status" as an optimal timing for completion of ADs (52.2 %), while other groups regard earlier periods as it. More than 95 % oncologist answered that cardiopulmonary resuscitation and mechanical ventilator are necessity items for ADs form, while around 70 % of other groups answered so. Multivariate analysis revealed that several factors including agreement with terminal disclosures and a positive attitude toward HPC were independently associated with necessity of ADs. CONCLUSIONS: We found that attitudes toward ADs among cancer patients, family caregivers, oncologists, and the general public were significantly different. Our study also suggests that favorable attitudes toward comfort end-of-life care and HPC are keys that influence the perceived need for ADs.

Attitudes of cancer patients, family caregivers, oncologists and members of the general public toward critical interventions at the end of life of terminally ill patients.

BACKGROUND: Whereas most studies have focused on euthanasia and physician-assisted suicide, few have dealt comprehensively with other critical interventions administered at the end of life. We surveyed cancer patients, family caregivers, oncologists and members of the general public to determine their attitudes toward such interventions. METHODS: We administered a questionnaire to four groups about their attitudes toward five end-of-life interventions--withdrawal of futile life-sustaining treatment, active pain control, withholding of life-sustaining measures, active euthanasia and physician-assisted suicide. We performed multivariable analyses to compare attitudes and to identify sociodemographic characteristics associated with the attitudes. RESULTS: A total of 3840 individuals--1242 cancer patients, 1289 family caregivers and 303 oncologists from 17 hospitals, as well as 1006 members of the general Korean population--participated in the survey. A large majority in each of the groups supported withdrawal of futile life-sustaining treatment (87.1%-94.0%) and use of active pain control (89.0%-98.4%). A smaller majority (60.8%-76.0%) supported withholding of life-sustaining treatment. About 50% of those in the patient and general population groups supported active euthanasia or physician-assisted suicide, as compared with less than 40% of the family caregivers and less than 10% of the oncologists. Higher income was significantly associated with approval of the withdrawal of futile life-sustaining treatment and the practice of active pain control. Older age, male sex and having no religion were significantly associated with approval of withholding of life-sustaining measures. Older age, male sex, having no religion and lower education level were significantly associated with approval of active euthanasia and physician-assisted suicide. INTERPRETATION: Although the various participant groups shared the same attitude toward futile and ameliorative end-of-life care (the withdrawal of futile life-sustaining treatment and the use of active pain control), oncologists had a more negative attitude than those in the other groups toward the active ending of life (euthanasia and physician-assisted suicide).

The Impacts of Prognostic Awareness on Mood and Quality of Life Among Patients With Advanced Cancer.

BACKGROUND: Accurate awareness of the prognosis is an important factor in the treatment decision of patients with advanced cancer; however, prognostic disclosure is still subject to debate because it can reduce patient's satisfaction and increase depression. AIM: The purpose of this study is to assess whether patients' prognostic awareness is associated with decreased quality of life (QoL) or increased depressive mood in patients with advanced cancer. DESIGN AND PARTICIPANTS: In this cohort study, 386 patients with advanced cancer were recruited across 3 periods from December 2016 to August 2018. The outcome of this study was a change in QoL and depression according to the patients' prognostic awareness at baseline, 3 months, and 6 months. RESULTS: This study found significant differences in changes of QoL based on patients' prognostic awareness. From baseline to 3 months, emotional functioning (P = .039), pain (P = .042), existential well-being (P = .025), and social support (P = .038) subscale scores improved significantly more in those with lack of prognostic awareness. Over 6 months, the group without prognostic awareness improved significantly in terms of physical functioning (P = .037), emotional functioning (P = .002), nausea/vomiting (P = .048), and constipation (P = .039) subscale scores and existential well-being scores (P = .025). No significant difference between the groups was found in terms of depression. CONCLUSION: Accurate prognostic awareness may pose harm and may provide no additional benefits in terms of QoL and mood among patients with advanced cancer for a short period of time.

A case of Wernicke's encephalopathy following fluorouracil-based chemotherapy.

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.

Factors That Influence Attitudes Toward End-of-Life Care Among Medical Students: Nationwide Survey for Fourth-Year Korean Medical Students.

BACKGROUND: Positive attitudes for end-of-life (EOL) care along with adequate education are key factors for the provision of quality EOL care. This national study was conducted to identify the factors that influence attitudes toward EOL care on medical students. METHOD: An anonymous survey was designed and administered to fourth-year medical students at all 41 medical schools in Korea. Topics related to EOL care were assessed in classroom teaching, bedside teaching, and feedback experiences during clinical clerkships. Seven questions for self-rated attitudes and affecting factors were analyzed toward EOL care. RESULTS: With a response rate of 49.2%, the median number of topics recognized by the students as having been delivered was 5 of 11 topics in classroom lectures and 1 of 8 topics in clinical experience. Although few (21.2%) participants indicated that they felt ready for EOL care practice, nevertheless, most felt that they should have adequate knowledge of and preparation for clinical competency in EOL care. Several parameters including respondent's demographics and exposure to EOL care topics in classroom and in bedside teaching influenced the responses to all 7 attitude questions. However, having more than 1 bedside experience was the only factor positively affecting all attitudinal measures. CONCLUSIONS: Clinical experience related to EOL care seems to be the utmost priory in fostering positive attitudes and competency among medical students.

Prognostic significance of CD44s expression in biliary tract cancers.

BACKGROUND: CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. METHODS: Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. RESULTS: Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival. CONCLUSIONS: CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

Attitudes toward early palliative care in cancer patients and caregivers: a Korean nationwide survey.

Integrated early palliative care (EPC) improves quality of life and reduces psychological distress in adult patients with cancer and caregivers, but attitudes toward EPC have been poorly studied. We aimed to investigate attitudes toward EPC in a nationwide survey of patients with cancer and caregivers. From July to October 2016, we administered nationwide questionnaires examining attitudes toward EPC in patients with cancer (n = 1001) and their families (n = 1006) from 12 Korean hospitals. When an individual considered EPC unnecessary, the reasons were collected and analyzed. Factors associated with perception of EPC were examined. A majority of patients (84.5%) and caregivers (89.5%) had positive attitudes toward EPC. The most common reasons for deeming EPC unnecessary were that EPC may be an obstacle to cancer treatment (patients: 37%; caregivers: 23%; respectively) or that they were not sure if EPC is beneficial (patients: 21%; caregivers: 24%; respectively). Financial burden as a reason was more evident in caregivers (23%) than in patients (17%). Male gender, age <50, early stage, intensive care unit admission, and not believing that dying people should prepare to practice charity were associated with patients' negative attitudes. In caregivers, opposition to EPC was associated with not thinking death should be feared, not thinking people should be remembered, and lower educational level. Our findings showed that significant numbers of patients with advanced cancer and family caregivers showed positive attitudes toward EPC. However, more than 10% of participants did not consider EPC necessary. Physicians' communication with patients and caregivers and financial support could help overcome the barriers of EPC.

Early imatinib-mesylate-induced hepatotoxicity in chronic myelogenous leukaemia.

Imatinib mesylate is the first molecule of targeted therapy in chronic myelogenous leukaemia inhibiting constitutively activated BCR-ABL kinase. There are no long-term follow-up studies of large sample sizes to assess the toxicity of the use of imatinib mesylate over 10 years. Several cases of hepatotoxicity, including fatal liver failure, have been associated with the long-term use of imatinib mesylate. We report here on a patient who experienced immediate dominant cholestatic damage of the liver and mild hepatocyte damage during imatinib mesylate therapy. This differs from most reports showing dominantly acute hepatitis with necrosis associated with the use of imatinib mesylate.

Do-not-resuscitate orders for terminal patients with cancer in teaching hospitals of Korea.

OBJECTIVES: To examine the current practices relating to do-not-resuscitate (DNR) orders for terminal patients with cancer at teaching hospitals in Korea. METHODS: The records of 387 deaths from January 1 to December 31, 2005 at four cancer centers were identified and reviewed to assess the DNR delineation. Basic demographics, circumstances surrounding the establishment of the DNR directive, the percentage of orders for identified populations, and the time interval between DNR consent and death were evaluated. RESULTS: An order of DNR consent was obtained from 296 patients (76%) of a total of 387 patients. All DNR consents were made between the physician and family, without involving the patient. Written preprinted DNR consent forms were used in 169 (57%) cases and 127 patients (43%) had verbal DNR permission. DNR consent was interpreted in two ways: one forbade resuscitation in two hospitals and the other implied limited care in two other hospitals. A unilateral physician decision to withhold cardiopulmonary resuscitation (CPR) was decided for 62 (16%) patients. Terminal CPR was performed on 29 (7%) patients. DNR discussion was made within 7 days of the day of death on 228 (77%) patient among the 296 DNR consenting patients. CONCLUSION: From our teaching-hospital-based analysis of terminal cancer patients in Korea, consent for a DNR order was common. However, DNR order forms were not standardized and lacked room to document patient involvement in the decision. Usually the DNR decision was made within last days of the patient's life. Our results reflect the need for the improvement of end-of-life care decisions in Korea.

Docetaxel plus epirubicin as first-line chemotherapy in MBC (KCSG 01-10-05): phase II trial and the predictive values of circulating HER2 extracellular domain and vascular endothelial growth factor.

The anthracyclines and taxanes are considered to be the most active drugs in metastatic breast cancer (MBC). We conducted a multicenter phase II study to evaluate the efficacy and tolerability of the docetaxel plus epirubicin combination chemotherapy as first-line treatment in MBC and performed a prospective assessment of the predictive values of circulating HER2 extracellular domain (ECD) and vascular endothelial growth factor (VEGF). Docetaxel 75 mg/m(2) and epirubicin 75 mg/m(2) were given intravenously every 3 weeks. Prophylactic G-CSF was not used. Pretreatment serum HER2 ECD and VEGF levels were measured by enzyme immunoassay. Forty MBC patients were enrolled, and 39 patients were evaluable for toxicities and 38 for response. Complete response was observed in 3 (7.9%) patients, partial response in 20 (52.6%) (overall response rate 60.5%), stable disease in 11 (28.9%) and disease progression in 4 (10.5%). After a median follow-up of 22.5 months, the median duration of response was 28 weeks, median time to disease progression was 32 weeks, and median survival was 15.8 months. Two-hundred and fifteen cycles of treatment were administered (median, 6 cycles per patient). Grade 3 and 4 neutropenia were observed during 24 (11.2%) and 74 (35%) cycles respectively, and grade 3 or 4 febrile neutropenia in 24 (11.2%) cycles. Elevated circulating HER2 ECD levels were found to be associated with a shorter response duration (p<0.005) and shorter time to progression (p<0.005). However, elevated VEGF levels were not found to be correlated with response rate or survival. We concluded that the docetaxel and epirubicin combination is an effective first-line treatment in MBC patients and that elevated serum HER2 ECD levels, but not circulating VEGF levels, predict a poor outcome.

Potential prognostic significance of p185(HER2) overexpression with loss of PTEN expression in gastric carcinomas.

AIMS AND BACKGROUND: The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185(HER2)) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity. The phosphatase and tensin homolog mutated on chromosome ten (PTEN) gene product is a protein tyrosine phosphatase that participates in modulating the phosphoinositide 3-kinase pathway which has antagonizing activity to protein tyrosine kinase. The authors investigated the correlation between clinicopathologic variables including survival and the overexpression of the p185(HER2) with loss of PTEN expression in gastric adenocarcinoma patients. METHODS: The protein expression of p185(HER2) and PTEN was examined by immunohistochemical stain in paraffin-embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using monoclonal antibody, and the results were related to clinicopathological variables and survival. RESULTS: p185(HER2) overexpression correlated positively with lymph node metastasis, distant metastasis, AJCC classification, higher relapse rate. Patients with overexpression of p185(HER2) were found to have significantly lower disease-free survival (P = 0.003) and overall survival (P = 0.0004). Loss of PTEN expression correlated positively with depth of invasion (T stage) and was more frequent in the advanced stage. The patient group with p185(HER2) overexpression and loss of PTEN expression showed significantly shorter disease-free and overall survival (P = 0.03, P = 0.01) than the other groups. CONCLUSIONS: Our observations suggest potential prognostic significance of p185(HER2) overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185(HER2)and PTEN as a therapeutic target in gastric cancer.

Novel Germline Mutation of BRCA1 Gene in a 56-Year-Old Woman with Breast Cancer, Ovarian Cancer, and Diffuse Large B-Cell Lymphoma.

We report a case of a 56-year-old woman with breast cancer, ovarian cancer, and diffuse large B-cell lymphoma with a BRCA1 gene mutation. Evidence is mounting that there is a large increase in the risk for hematologic malignancies among patients with genetic changes in the BRCA pathways. The genomic analysis demonstrated a frameshift mutation in the BRCA1 gene: 277_279delinsCC (Phe93fs). It is a novel BRCA1 mutation that has never been reported, and caused malignant lymphoma as well as breast and ovarian cancer.