Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer

To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.     

Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system--the second report

Intra-arterial infusion chemotherapy via an implantable port catheter has been applied in 16 patients with locally recurrent breast cancer. The regimen consisted of induction and subsequent maintenance: intra-arterial infusion of epirubicin (EPI). Non-responders were entered into the second-line regimen consisting of Methotrexate and 5-FU (MF). The results were as follows: 1) The response rate (CR+PR) of EPI to locoregional lesions was 50%, and the median duration of response was 5.7 months. 2) The response rate and the duration of response of MF were 25% and 3 months, respectively. 3) Patients with ER-rith, no previous therapy and a long disease-free interval tended to have a high rate of response to intra-arterial infusion therapy. 4) Improvements of QOL, such as intractable pain, infection and severe lymphedema were recognized in 68.6% of the cases. In more than half of the cases, these treatments were carried out in an outpatient clinic. 5) Leucopenia and catheter or portal problems were encountered in 68.6% and 25.0%, respectively. We conclude that intra-arterial infusion chemotherapy via implantable system is a promising modality with regard to therapeutic effect and improvement of quality of life.     

Intra-arterial infusion chemotherapy for advanced endometrial cancer before surgical treatment

Nine cases of advanced uterine body cancer (stage III: 8, stage IVa: 1) were treated by intra-arterial infusion chemotherapy before curative operation. This treatment produced primary tumors smaller than half sizes in eight cases. Necrotic changes were found in over two-thirds of the lesions in six cases. This chemotherapy enabled us to operate curatively in seven cases. After the operations, we performed various types of treatment including intra-arterial infusion chemotherapy. No evidences of disease have been found in four cases, but there is no significant difference between the groups receiving and not receiving the intra-arterial infusion chemotherapy (n = 16) in terms of survival rate of stage III. Further study of the prognosis is necessary.     

Intra-arterial infusion chemotherapy for advanced uterine cancer before surgical treatment

We reported a case of an abrupt hypotension and hypoxemia which lasted more than 60 min due to emboli of tumor at the orifice of the pulmonary artery during operation. Although the emboli were removed under the cardiopulmonary bypass (CPB) and later the patient regained good respiratory and hemodynamic conditions, he had a disturbance of consciousness after the operation. We began oxygen hyperbaric therapy (OHP) from the 6th postoperative day under spontaneous ventilation. His consciousness improved quickly after the beginning of OHP. We conclude that OHP and CPB might be useful to treat the postoperative disturbance of consciousness due to hypotension and hypoxemia during operation.     

Effect of CDDP/5'-DFUR combination chemotherapy for advanced or recurrent gastric cancer

CDDP/5'-DFUR combination chemotherapy was performed on 17 patients with non-resected and recurrent gastric cancer (clinical stage were IVb in all patients). They were treated with 1,400 mg/m2 of 5'-DFUR on days 1-4 orally following by withdrawal 10 days, every 2 weeks repeatedly and 80 mg/m2 of CDDP (c. i. v., on day 5, every 4 weeks). This chemotherapy was performed for at least 2 courses on all patients. Eight of 17 patients achieved a partial response and the overall response rate was 47.1% (differentiated type 57.1%, undifferentiated type 45.5%). Response rates of each lesion were as follows: primary foci 42.9%, abdominal lymph nodes 57.1%, hepatic metastasis 60.0% and ascites 33.3%, respectively. Improvement of performance status was seen in 12 of 17 patients (70.6%). The overall median survival time was 227 days. The median outpatient period was 113 days. There was no high-grade toxicity over grade 2. Therapeutic toxicity of grade 2 was manifested as renal dysfunction (23.5%), nausea/vomiting (17.6%), leukopenia (5.9%) and anemia (5.9%). We evaluated the therapeutic effect by visual examination after completion of the second course. However, poor effect and high incidence of renal dysfunction were found in patients treated with this therapy over four times. Therefore, the maximum effect seemed to be revealed after completion of the fourth course. From the present study, CDDP/5'-DFUR combination chemotherapy seems to be effective for patients with high-grade advanced gastric cancer and improved their quality of life.     

Weekly CAF chemotherapy for advanced breast cancer patients

BACKGROUND: Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer. Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced, without increasing shoulder dysfunction, by delayed postoperative shoulder exercises. METHODS: In a prospective study 163 patients with breast cancer undergoing modified radical mastectomy were randomized to physiotherapy starting on postoperative day 1 or day 7. Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department. Seromas and other complications were registered by the surgeons. The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function. RESULTS: There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 (38%) compared to the group that started physiotherapy postoperative day 7 (22%) (p < 0.05). There was no significant difference between the groups in the late outcome of shoulder function. CONCLUSION: The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.     

An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy

We treated randomly 75 premenopausal patients with advanced breast cancer with combination chemotherapy (5-fluorouracil, cyclophosphamide and prednisone), either as an early adjunct to oophorectomy or as a delayed treatment upon appearance of progressive metastatic disease after operation. The group receiving early systemic chemotherapy enjoyed an improved response rate, an improved survival rate and, most importantly, an improved progression-free interval (median of 53 versus 17 weeks). With the exclusion of the group with early (within three weeks after oophorectomy) progression, the progression-free intervals had a median duration of 77 weeks in the early-treatment group versus 33 weeks in the control group. The early-progression group did exceedingly poorly, although systemic chemotherapy was employed at that juncture, having a median survival of 22 weeks as compared to 144 weeks in the immediate-treatment group and 105 weeks in the control group.     

Do patients with advanced breast cancer benefit from chemotherapy?

This study aimed to assess the proportion of patients with advanced breast cancer who report benefit from first-line palliative chemotherapy using a simple global measure of wellbeing and to identify factors predicting benefit. A consecutive series of women with advanced breast cancer undergoing first-line palliative chemotherapy was evaluated. The main outcome measure was patient report of overall wellbeing assessed at post-treatment interview. Physical, psychological and functional status were assessed using the Rotterdam Symptom Checklist (RSCL) on three occasions (pretreatment, at the start of the third cycle and post treatment). It was planned that treatment would be discontinued after six cycles (i.e. 18-24 weeks). One hundred and sixty patients started treatment, of whom 155 were assessable for quality of life. After treatment, 41 (26%) patients reported they felt better, 29 (19%) felt the same and 34 (22%) felt worse than they did before treatment. The other 51 (33%) patients either died or stopped attending the hospital before the post-treatment interview and were assigned as treatment 'failures'. Patients who reported feeling better after treatment had improvements in psychological distress (P < 0.0001), pain (P = 0.01), lack of energy (P = 0.02) and tiredness (P = 0.02), as well as improvement in functional status (P = 0.07). Feeling better was also correlated with disease response (P = 0.03). Feeling worse after treatment or treatment 'failure' was predicted by the pretreatment presence of a dry mouth (P = 0.003) and high levels of psychological distress (P = 0.03). Pretreatment lack of energy (P = 0.01), dry mouth (P = 0.02), presence of liver metastases (P = 0.03) and breathlessness (P = 0.03) predicted treatment 'failures'. The results of this study suggest that first-line palliative chemotherapy for advanced breast cancer confers benefit on a substantial proportion of patients, with about one-quarter feeling better after treatment and nearly a half feeling better or the same some 4-6 months after the start of treatment. Factors identified in this study may assist clinicians in deciding which patients should not be offered treatment, because of high risk of feeling worse or treatment 'failure'. This work now needs to be validated on a further cohort of women receiving chemotherapy for advanced breast cancer.     

Quality of life and pain in patients with recurrent breast and gynecologic cancer

The kinetic mechanisms of the binding to tubulin of colchicine and eight different analogues have been studied to elucidate details of the recognition mechanism. All of the analogues follow a two step binding mechanism i.e. binding occurs via an initial step with low affinity, followed by an isomerisation of the initial complex leading to the final high affinity state. For several analogues the kinetic and thermodynamic data of both processes are compared here. For all the analogues the delta G1 degree of initial binding at 25 degrees C varies between -13.3 and -28.8 kJ. mol-1. For the second step delta G2 degrees varies between -2.4 and -27 kJ. mol-1. These limited ranges of free energy change are, however, obtained by a great variety of enthalpy changes and compensatory entropy changes. Comparison of the data for the first and second steps indicates that structural alterations of the drugs always change the thermodynamic parameters of the two steps, and the changes in the first and the second steps are in opposite directions. The fact that this range of experimental behaviour can be incorporated into a general mechanism encourages the extension of these investigations to other colchicine analogues and related compounds with potential pharmaceutical applications.     

Involvement in decision-making and breast cancer survivor quality of life.

Objective: This study examined the long-term effects on women's health related quality of life (HRQOL) of involvement in decision-making about their treatment for breast cancer and about follow-up care after treatment. Methods: Using a cross-sectional survey design, a sample of breast cancer survivors from Western Washington who were 2, 5, and 10 years postdiagnosis were recruited via a cancer registry and interviewed about their HRQOL and their involvement in decision-making about their cancer treatment and follow-up care. Main Outcome Measures: HRQOL was assessed using the SF-36. Results: Multiple regression analyses examining demographic and disease characteristics revealed age, and education, but not stage of cancer at diagnosis, to be significant predictors of perceived involvement in decision-making about cancer treatment and follow-up. Controlling for demographic and disease characteristics, perceived involvement in decision-making about treatment overall, surgery, chemotherapeutic treatment, and follow-up care were each associated with improved HRQOL, including the general health and vitality subscales of the SF-36 (p     

Outpatient chemotherapy of advanced breast cancer in a community setting: a five-drug regimen

Forty-two (37 evaluable) unselected women with advanced breast carcinoma were treated with a modified "Cooper regimen" in a community setting. After 12 weeks of induction therapy, the patients were evaluated for response and toxicity. The 74% overall response rate (78% in the evaluable group) compares favorably with that of other series. The median duration of remission was 13.7 months. The median survival was 17 months for the evaluable patients and 14 months for the entire group. Twenty-two percent of the patients required hospitalization during the induction phase, and 35% were treated exclusively as outpatients during all phases of therapy. There was only one drug-related death. It is concluded that a complex chemotherapeutic regimen can be managed adequately by physicians experienced in chemotherapy in a community setting with results comparable to those from cancer centers.     

Toxicity and therapeutic response to chemotherapy in patients aged 70 years or older with advanced cancer

To evaluate the impact of chemotherapy in terms of feasibility and activity in elderly patients, we treated 120 patients aged 70 years or older with advanced cancer in six major organ sites (breast, colorectum, lung, stomach, ovary, and head and neck). Furthermore, we compared the results in this age group with those in 120 patients with similar clinical features receiving the same chemotherapeutic combinations but whose age was under 70. Our results show that chemotherapeutic regimens routinely used in younger patients yield the same benefits and levels of toxicity in older patients. In none of the different organ sites, in fact, did we observe a higher incidence or severity of side effects, nor were there differences in response rate and survival. In conclusion, elderly cancer patients who are not suffering from medical complications, which are generally increased in aged patients (e.g., cardiovascular, pulmonary, renal, or neurological diseases), can be considered candidates for full doses of chemotherapy, like their younger counterparts.     

bcl-2 but not p53 expression is associated with resistance to chemotherapy in advanced breast cancer

Programmed cell death is an important determinant of the response to chemotherapy. Among the factors controlling this process, a significant role is played by bcl-2 and p53, the expression of which, together with estrogen receptor content and tumor proliferative activity, was investigated by means of immunohistochemistry in 55 advanced breast cancer patients (median age, 60 years; range, 25-71 years). Analysis of bcl-2 expression identified two groups of patients with a significant difference in response rate. A total of 17 patients (31%) responded to chemotherapy (5 had a complete response and 12 had a partial response): 14 of 32 (44%) bcl-2-negative patients (< 40% stained cells) and only 3 of 23 (13%) bcl-2-positive patients (> or = 40% of stained cells; P = 0.019 by Fisher's exact test). The two groups were well balanced in terms of age, performance status, disease-free survival, menopausal status, and type of chemotherapy. bcl-2-negative tumors showed a tendency toward a higher p53 expression and proliferation rate, whereas an excess of bone as the dominant disease site was evident among the bcl-2-positive ones. However, the only variable to result significantly different between the two groups was estrogen receptor expression (P = 0.004). A multivariate logistic regression model showed that bcl-2 maintained its power of discriminating two groups with a different probability of responding to chemotherapy, although the greatest contribution was given by dominant disease site and type of chemotherapy. In conclusion, the results of this study suggest a possible role for bcl-2 in predicting resistance to chemotherapy.     

A comparative study of 4 sequential first-line chemotherapy protocols in locally advanced breast cancer]

The toxic effect of Silesian air pollutants to mouse organs was examined. Histological changes were found in the examined lymphoid organs (thymus, spleen) as well nonlymphoid organs (liver, kidneys). The alterations in weight indexes of lymphoid organs were also observed. Considerable changes in cellularity, weight index, and histology of the thymus in the mice exposed to air pollutants suggest the atrophy of this organ, which may lead to extrathymic T-cell differentiation and even acceleration of thymocytes maturation, which may lead to certain allergic or auto-immune pollutants of all investigated mouse organs in the following order: thymus, liver, kidneys, and spleen.     

Adjuvant chemotherapy of breast cancer

Numerous randomized trials have been conducted in an attempt to demonstrate the role of adjuvant chemotherapy in localized operable breast cancer. A major meta-analysis has demonstrated its effectiveness in certain indications. These trials show that only long-term combination chemotherapy has an undeniable efficacy. The reference protocol is the classical CMF combining cyclophosphamid, methotrexate and 5 fluoro-uracil. Efficacy is clear for patients under 50 years of age. After this age, tamoxifen is effective. There does not appear to be any benefit from prolonging chemotherapy over 6 months. The meta-analysis has not however answered all the questions raised by adjuvant chemotherapy. Should chemotherapy be used in N-forms? What is the effect of treatment in patients over 65? What is the optimal treatment duration? Is there a dose-efficacy relationship? What is the relative effect of chemotherapy versus radiotherapy? Does perioperative chemotherapy add any benefit? What should be the relative roles of hormone therapy and chemotherapy? Is castration as effective as chemotherapy before menopause and tamoxifen after menopause? Currently, only partial answers to these questions have been obtained and many remaining problems will only be solved by the results of controlled trials currently under way.     

Intrusiveness of illness and quality of life in young women with breast cancer

Respiratory chain complex I is a complicated enzyme of mitochondria, that couples electron transfer from NADH to ubiquinone to the proton translocation across the inner membrane of the organelle. The fungus Neurospora crassa has been used as one of the main model organisms to study this enzyme. Complex I is composed of multiple polypeptide subunits of dual genetic origin and contains several prosthetic groups involved in its activity. Most subunits have been cloned and those binding redox centres have been identified. Yet, the functional role of certain complex I proteins remains unknown. Insight into the possible origin and the mechanisms of complex I assembly has been gained. Several mutant strains of N. crassa, in which specific subunits of complex I were disrupted, have been isolated and characterised. This review concerns many aspects of the structure, function and biogenesis of complex I that are being elucidated.