Mayumi Ishida

Treatment and Prognosis of Breast Cancer Patients with Brain Metastases According to Intrinsic Subtype

OBJECTIVE How breast cancer subtypes should affect treatment decisions for breast cancer patients with brain metastases is unclear. We analyzed local brain metastases treatments and their outcomes according to subtype in patients with breast cancer and brain metastases. METHODS We reviewed records and database information for women treated at the National Kyushu Cancer Center between 2001 and 2010. Patients were divided into three breast cancer subtype groups: Luminal (estrogen receptor positive and/or progesterone receptor positive, but human epidermal growth factor receptor 2 negative); human epidermal growth factor receptor 2 positive and triple negative (estrogen receptor negative, progesterone receptor negative and human epidermal growth factor receptor 2 negative). RESULTS Of 524 advanced breast cancer patients, we reviewed 65 (12%) with brain metastases and records showing estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status, as well as outcome data; there were 26 (40%) Luminal, 26 (40%) had human epidermal growth factor receptor 2 and 13 (20%) had triple negative subtypes. There was no statistical difference in the number of brain metastases among subtypes; however, rates of stereotactic radiosurgery or surgery for brain metastases differed significantly by subtype (human epidermal growth factor receptor 2: 81%, Luminal: 42% and triple negative: 47%; P = 0.03). Patients having the human epidermal growth factor receptor 2 subtype, a performance status of ≤1 and ≤4 brain metastases, who underwent systemic therapy after brain metastases and underwent stereotactic radiosurgery or surgery, were predicted to have longer overall survival after brain metastases. Multivariate analysis demonstrated that not having systemic therapy and not having the human epidermal growth factor receptor 2 subtype were independent factors associated with an increased risk of death (hazard ratio 2.4, 95% confidence interval 1.01-5.6; P = 0.05 and hazard ratio 2.9, 95% confidence interval 1.5-5.8; P = 0.003, respectively). CONCLUSION Our study showed that local brain treatments and prognosis differed by subtype in breast cancer patients with brain metastases.

The evaluation of the relationship between the level of disclosure of cancer in terminally ill patients with cancer and the quality of terminal care in these patients and their families using the Support Team Assessment Schedule.

Aims: To examine the relationship between informing patients of cancer and the quality of terminal care. Methods: This was a study of 87 consecutive terminally ill cancer patients who died during the last 27-month period. Notification of cancer was classified into 4 groups (A, B, C, and D, respectively): “nondisclosure,” “disclosure of cancer diagnosis,” “disclosure of life threatening,” and “disclosure of poor prognosis.” We evaluated the quality of palliative care using Support Team Assessment Schedule–Japanese (STAS-J). Results: A, B, C, and D groups included 8, 22, 37, and20 cases, respectively. Regarding physical symptoms, no marked difference was noted. Anxiety was significantly reduced, and the recognition of disease conditions and the level of communication were significantly higher in the groups that received specific information (P < .001). Conclusions: Informing patients of more specific information will increase the quality of terminal care.

Early detection and successful treatment of Wernicke encephalopathy in a patient with advanced carcinoma of the external genitalia during chemotherapy.

OBJECTIVE Few reports of Wernicke encephalopathy in oncological settings have been published. Some cases of Wernicke encephalopathy are related to appetite loss; however, the degree to which loss of appetite leads to thiamine deficiency is not known. METHOD A 63-year-old female with advanced cancer of the external genitalia was referred for psychiatric consultation because of disorientation, insomnia, and bizarre behaviors. Her symptoms fulfilled the diagnostic criteria for delirium. Routine laboratory examinations did not reveal the cause of the delirium. Thiamine deficiency was suspected because appetite loss had continued for 19 days since she had been admitted to hospital. RESULTS Intravenous administration of thiamine resulted in recovery from the delirium within three days. Serum thiamine level was found to be 16 ng/ml (normal range: 24-66 ng/ml). The clinical findings, the low level of thiamine in the serum, and the effective alleviation of delirious symptoms after thiamine administration fulfilled Franciss criteria for delirium induced by thiamine deficiency. SIGNIFICANCE OF RESULTS Clinicians must be aware of the possibility of Wernicke encephalopathy in cancer patients, especially in those with loss of appetite for longer than 18 days. The degree of appetite loss in such patients might serve as a reference. Early detection and intervention may alleviate the symptoms of delirium and prevent irreversible brain damage.

Care evaluation scale-patient version: measuring the quality of the structure and process of palliative care from the patient's perspective.

CONTEXT Recently, greater emphasis has been placed on patient-reported outcomes. However, there are only a few measures to evaluate the quality of care from the patients perspective. OBJECTIVES To report the development of a scale to measure the quality of the structure and process in palliative care from the patients perspective and examine the reliability and validity of the scale. METHODS A cross-sectional anonymous questionnaire was administered to cancer patients who were being treated on an oncology inpatient ward, who visited an oncology outpatient clinic at Saitama Medical University International Medical Center, or who were in an inpatient palliative unit in Japan between August 2007 and March 2008. RESULTS A total of 405 cancer patients participated in the study. Factor analysis revealed that the Care Evaluation Scale-Patient version (CES-P) consisted of 23 items with eight subscales: physical care by physicians, physical care by nurses, psychoexistential care, help with decision making for patients, environment, cost, availability, and coordination/consistency. The total CES-P score was correlated with satisfaction (r = 0.63) but not with quality of life (r = 0.18). The Cronbach α coefficient of the total score was 0.97, and the intraclass correlation coefficient of the total score was 0.67. The CES-P total score was not significantly correlated with the self-reported Eastern Cooperative Oncology Group performance status (ρ = -0.05). CONCLUSION The CES-P has sufficient validity and reliability. In addition, this scale is independent of the general physical condition of the patient.

Independent Validation of the Japanese Version of the EORTC QLQ-C15-PAL for Patients With Advanced Cancer

CONTEXT Although the psychometric properties of the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL) have been examined previously, that study had several limitations, for example, small sample size. OBJECTIVES To examine the validity and reliability, including test-retest reliability, of the Japanese version of EORTC QLQ-C15-PAL for cancer patients with metastasis or recurrence. METHODS A cross-sectional anonymous questionnaire was administered to cancer patients who were being treated on an oncology inpatient ward, in an oncology outpatient clinic, and in seven inpatient palliative units in Japan, from August 2007 to March 2008. RESULTS Data from a total of 312 cancer patients were analyzed. The proportion of missing values was less than 4% for all items. The factor structure was reproduced identically with the original EORTC QLQ-C15-PAL, English version. The correlation of subscales showed a reasonable matrix. Cronbachs alpha coefficients were 0.76 to 0.86, and intraclass correlation coefficients, which indicate test-retest reliability, ranged from 0.52 to 0.77. All subscales, especially physical functioning, fatigue, and pain, were significantly correlated with self-reported Eastern Cooperative Oncology Group performance status. CONCLUSION The Japanese version of EORTC QLQ-C15-PAL has sufficient validity, acceptable reliability, and feasibility for patients with advanced cancer.

Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature.

Abstract The roles of aromatase inhibitors (AIs) and luteinizing hormone–releasing hormone (LH–RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH–RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH–RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH–RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH–RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH–RH agonist. AIs with or without an LH–RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer.

Cytogenetic analysis of metaplastic squamous cell carcinoma of the breast inter- and intratumoral heterogeneity

BackgroundSquamous cell carcinoma (SCC) of the breast is a rare and generally aggressive disease that accounts for less than 0.1% of all breast carcinomas. Although SCCs have distinct morphological features, their origin and cytogenetic profile are not well understood.MethodsFive patients with SCC were studied. The tumor area that was predominantly composed of SCC components was macrodissected and DNA was extracted. In three cases, an invasive or noninvasive ductal carcinoma of no special type (NST) component was also present. NST-component DNA was also extracted. The tumor DNA was used for array comparative genomic hybridization analysis using a high-density oligonucleotide microarray. The cytogenetic profile of the SCC components was compared with each other and with the paired NST component in three of the five cases.ResultsThe cytogenetic profile of the SCC components indicated large intertumoral heterogeneity. There were between 2 and 160 copy number alterations per case, and no common copy number alterations were identified. The cytogenetic profiles of the paired SCC and NST components were similar but not identical. Although, in one case, a larger number of copy number aberrant regions were detected in the SCC component than the NST component. In this case, all the NST component aberrations were present in the SCC component. This implies that the SCC component originated from the NST component. There were no common SCC component-specific aberrations in the three NST-component cases.ConclusionOur results demonstrate the cytogenetic inter- and intratumoral heterogeneity of SCC of the breast. Our comparison of cytogenetic profiles indicated that the SCC component originated from the NST component in one case.

Development and validation of the Comprehensive Quality of Life Outcome (CoQoLo) inventory for patients with advanced cancer

Background The purpose of this study was to develop a scale capable of measuring comprehensive quality of life (QOL) outcomes based on the concept of a good death for patients with advanced cancer. Methods We conducted an anonymous cross-sectional questionnaire survey on inpatients being treated at the Oncology Clinic in Saitama Medical University International Medical Center and seven palliative units throughout Japan. Results A total of 405 patients with cancer participated in this study. Factor analysis of scores on the Comprehensive Quality of Life Outcome (CoQoLo) inventory revealed 28 items and the following 10 subscales: physical and psychological comfort; staying in a favourite place; maintaining hope and pleasure; good relationships with medical staff; not being a burden to others; good relationships with family; independence; environmental comfort; being respected as an individual; and having a fulfilling life. The total CoQoLo score was moderately correlated with satisfaction (r=0.34) and overall QOL (r=0.34), and moderately correlated with feelings of support and security regarding cancer care (r=0.44). Cronbachs α and the intraclass correlation coefficient of the total score were 0.90 and 0.79, respectively. No significant correlation was found between the total CoQoLo score and self-reported Eastern Cooperative Oncology Group performance status (r=−0.01). Conclusions These results suggest that the CoQoLo has sufficient reliability and validity and therefore provides an accurate measure of QOL outcomes independent of the general physical condition of the patient.

Drug-induced akathisia as a cause of distress in spouse caregivers of cancer patients.

OBJECTIVE Family caregivers of cancer patients suffer from physical, psychological, and social distress and therefore are often referred to as second order patients. Akathisia is a common side effect of antipsychotics and antidepressants that causes great discomfort and even agitation and is often described by patients administered these drugs as the most distressing side effect of their treatment. Several studies of akathisia as a cause of distress in cancer patients have been reported. However, akathisia has not been reported as a cause of distress in family caregivers of cancer patients. METHOD/CASE REPORT A 74-year-old spouse caregiver who was under treatment for major depressive disorder was not able to visit the hospital where her husband, a terminally ill cancer patient, was being treated. Initially, the spouse caregiver thought that she could not visit the hospital because of the symptoms of her depression and her grief about losing her husband. However, careful clinical examination revealed that she was suffering from akathisia in addition to her grief. RESULTS Discontinuation of her sulpiride treatment resulted in the disappearance of her akathisia symptoms, and therefore she became able to visit the hospital and care for her terminally ill husband. SIGNIFICANCE OF RESULTS Drug induced akathisia is a cause of distress in spouse caregivers taking certain drugs. It is important for clinicians to realize that family caregivers might suffer from not only socioeconomic, physical, and psychological problems but also side effects of medication.

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

BackgroundNeoadjuvant chemotherapy (NAC) is the standard therapeutic strategy for triple-negative breast cancer (TNBC). TNBC patients with residual disease after NAC have a significantly worse survival than those with pathological complete response (pCR); however, there is no apparent prognostic factor for non-pCR patients. Cancer stemness or epithelial–mesenchymal transition (EMT) might influence the sensitivity to chemotherapy.Patients and methodsForty-eight patients with TNBC who were treated with NAC were available were included in this study. The expressions of stemness marker CD44v9, EMT marker vimentin and BRCA1, and basal phenotype were evaluated with immunohistochemistry. The relationships between the expression of these proteins and the pCR rate and the prognosis, especially in the patients with residual tumors, were investigated.ResultsAmong the 48 patients, pCR was achieved in 14 cases. High nuclear grade and basal phenotype in the pre-NAC samples were significantly correlated with pCR (p = 0.0458 and 0.0343). There were no significant relationships between the pCR rate and the expression of CD44v9, vimentin, or BRCA1. Achieving pCR was significantly correlated with longer distant metastasis-free survival (DMFS) (p = 0.0206). High CD44v9 expression was significantly associated with shorter DMFS (p = 0.0291). Among the patients in whom pCR was not achieved, high grade in the residual tumor cells, poor pathological response and high CD44v9 expression in the pre-treatment CNB samples were significantly correlated with a poor DMFS (p = 0.0433, 0.0406 and p = 0.0333). In addition, high grade in the residual tumor cells was significantly associated with high CD44v9 expression in the pre-treatment CNB (p = 0.0389).ConclusionsHigh CD44v9 expression in pre-NAC samples was associated with poor prognosis in TNBC patients treated with NAC, especially for those in whom pCR was not achieved.