Cancer Patients Undergoing Adjuvant Therapy Research Articles

The self-management instrument for breast cancer patients undergoing adjuvant therapy: Development and psychometric testing using the COSMIN methodology

ObjectiveThis study aims to develop and test the self-management instrument for breast cancer patients undergoing adjuvant therapy (SMAT-B). MethodsAfter a qualitative interview with 29 patients and two rounds of Delphi expert consultation with 15 experts, 49 items were initially generated. Before item reduction, another structured interview was conducted for content validity. Item analysis and exploratory factor analysis (n ​= ​377) were used for item reduction. After that, internal consistency, split-half reliability, test-retest reliability (n ​= ​30), measurement error, construct validity, and structural validity (n ​= ​342) were preliminarily evaluated using the COnsesus-based Standards for the selection of health Measurements INstruments guidelines. ResultsThe final version of SMAT-B includes 7 dimensions and 31 items after item reduction. The testing results suggested that SMAT-B had good internal consistency (Total Cronbach's α ​= ​0.952), good split-half reliability (Spearman-Brown coefficient ​= ​0.904), good stability (Total intraclass correlation coefficient = ​0.797), acceptable measurement error (SEM ​= ​5.28), and acceptable construct validity (Standardized root mean square residual ​= ​0.055). The hypotheses of construct validity were all verified to a certain extent (r ​> ​0.20, P ​< ​0.01). ConclusionsThe 31-item SMAT-B, developed in interviews with patients and consultation with experts, demonstrated good psychometric properties and can be recommended for researchers and clinicians for further validity testing and evaluation of the self-management ability of breast cancer patients. Trial registrationChiCTR2100052868.

Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma.

Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes using genetic and pharmacological approaches, we demonstrated the existence of active competition between 2HG producing enzymes, i.e., IDH2 and ADHFE1. Moreover, we showed that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release in the urine of breast cancer patients undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma.

New Strategy of Home-Based Exercise during Pandemic COVID-19 in Breast Cancer Patients: A Case Study

The COVID-19 pandemic has posed several challenges for the oncology health care system. The need to improve patients’ Quality of Life (QoL) through exercise, which is related to survival and healing, has increased, especially during lockdowns. Technologies are often used to help with patient care as well as to monitor exercise training. This case study, developed during the pandemic period, aims to evaluate the effectiveness of a proposed home-based combined training (CT) regimen, supervised through online lessons, in increasing QoL and fatigue in breast cancer patients undergoing adjuvant therapy. Additionally, we evaluated the effect of exercise on psychological and functional parameters. Methods: Two breast cancer (BC) survivors were required to participate in 2 h/week of supervised and home-based CT for 16 weeks. Results: Improvements were found in the emotional function of QoL (10% in patient A; 70% in patient B) and in all variables of fatigue (physical fatigue 66% in patient A; 33% in patient B). Conclusion: The findings from this study revealed positive effects of CT on QoL and fatigue perception in BC women undergoing therapy. Both patients attended all training sessions with no adverse events, showing the sustainability of this training as an alternative and affordable method that is capable of improving patients’ wellbeing.

Heavy Resistance Training in Breast Cancer Patients Undergoing Adjuvant Therapy.

Adjuvant breast cancer therapy may reduce maximal muscle strength, muscle mass, and functional performance. Although maximal strength training (MST) has the potential to counteract this debilitating outcome and is shown to be superior to low- and moderate-intensity strength training, it is unknown if it can elicit effective adaptations in patients suffering treatment-induced adverse side effects. Fifty-five newly diagnosed stage I to III breast cancer patients (49 ± 7 yr) scheduled for adjuvant therapy were randomized to MST or a control group. The MST group performed 4 × 4 repetitions of dynamic leg press at approximately 90% of one-repetition maximum (1RM) twice a week for 12 wk. In the MST group, improvements in 1RM (20% ± 8%; P < 0.001) were accompanied by improved walking economy (9% ± 8%) and increased time to exhaustion during incremental walking (9% ± 8%; both P < 0.01). Moreover, the MST group increased 6-min walking distance (6MWD; 10% ± 7%), and chair rising (30% ± 20%) and stair climbing performance (12% ± 7%; all P < 0.001). All MST-induced improvements were different from the control group (P < 0.01) which reduced their 1RM (9% ± 5%), walking economy (4% ± 4%), time to exhaustion (10% ± 8%), 6MWD (5% ± 5%), chair rising performance (12% ± 12%), and stair climbing performance (6% ± 8%; all P < 0.01). Finally, although MST maintained estimated quadriceps femoris muscle mass, a decrease was observed in the control group (7% ± 10%; P < 0.001). The change in 1RM correlated with the change in walking economy (r = 0.754), time to exhaustion (r = 0.793), 6MWD (r = 0.807), chair rising performance (r = 0.808), and stair climbing performance (r = 0.754; all P < 0.001). Lower-extremity MST effectively increases lower-extremity maximal muscle strength in breast cancer patients undergoing adjuvant therapy and results in improved work economy, functional performance, and maintenance of muscle mass. These results advocate that MST should be considered in breast cancer treatment.

The effects of Pythagorean Self-Awareness Intervention on breast cancer patients undergoing adjuvant therapy: A pilot randomized controlled trial

IntroductionBreast cancer patients undergo extended treatments that affect their psychological state and quality of life. There is a lack of studies examining the effects of holistic stress management interventions (that combine stress perception, cognitive and lifestyle interventions) on mental health and biological indices (e.g. cortisol concentrations) of breast cancer patients. Materials and methodsThis pilot randomized controlled trial provided the first assessment of the effects of a novel, cognitive-based intervention, the Pythagorean Self-Awareness Intervention (PSAI), on psychological symptoms, quality of life, sleep quality and lifestyle as well as on stress-related biological measures of breast cancer patients undergoing adjuvant therapy. Standardized questionnaires were administered at baseline and 8-weeksafter the intervention to evaluate quality of life, stress, depression, and anxiety (primary outcomes). Sleep quality, lifestyle and hair cortisol concentrations were also assessed (secondary outcomes). ResultsForty-five breast cancer patients undergoing adjuvant therapy were randomly assigned to the PSAI group (n = 25) or the control group (n = 20).Women in the PSAI group reported significant improvements post-intervention in total Quality of Life, specific aspects of Quality of Life [Physical well-being, Social well-being, Emotional well-being, Functional well-being, Breast cancer concerns] as well as Perceived stress, depression, anxiety and stress. Improvements in secondary outcomes included increase in sleep quality, empowerment for healthy lifestyle and reduction of hair cortisol concentrations. ConclusionsThe PSAI was beneficial as complementary therapy in the women studied. Larger randomized controlled trials with longer follow-up are needed to ascertain these findings.

No Evidence for Effect of Exercise on Transcriptome of NK Cells in Breast Cancer Patients Undergoing Adjuvant Therapy: Results From a Pilot Study.

BackgroundMobilization and activation of natural killer cells (NK cells) have been hypothesized to contribute to observed protective effects of exercise on cancer development and progression. Some evidence exists for acute effects of aerobic exercise on NK cell mobilization and function, i.e., alteration of the gene expression profile of NK cells. Yet, the chronic effects of exercise training, and effects of other modalities than endurance exercise are still understudied. Here, we investigated the chronic effects of a 12-week resistance exercise program on NK cell gene expression in breast cancer patients undergoing adjuvant chemo- or radiotherapy.MethodsBreast cancer patients were randomly assigned to either a 12-week resistance exercise program or a relaxation control group concomitant to adjuvant therapy. In a subsample of 19 participants, RNA was extracted from magnet bead isolated NK cells and subsequently analyzed for differential gene expression using microarray Illumina HumanHT-12 v4 before and after the intervention.ResultsAfter chronic exercise intervention several genes showed higher differential expression compared to the control group. However, after correction for multiple testing, baseline-adjusted analyses of covariance indicated no significant differences between the intervention and the control group with regard to the gene expression profile.DiscussionOur findings suggest that 12-week resistance-exercise did not alter the gene expression profile of NK cells in breast cancer patients undergoing adjuvant therapy on the long term. Further studies with larger sample sizes and specifically designed to investigate whether exercise-induced changes in NK cell function are attributed to acute effects are warranted.

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.

Paradoxical Association of Postoperative Plasma Sphingosine-1-Phosphate with Breast Cancer Aggressiveness and Chemotherapy.

Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that has been shown to serve an important regulatory function in breast cancer progression. This study analyzes plasma S1P levels in breast cancer patients undergoing adjuvant therapy as compared to healthy control volunteers. 452 plasma S1P samples among 158 breast cancer patients, along with 20 healthy control volunteers, were analyzed. Mean S1P levels did not significantly differ between cancer patients and controls. Smoking was associated with higher S1P levels in cancer patients. Baseline S1P levels had weak inverse correlation with levels of the inflammatory mediator interleukin- (IL-) 17 and CCL-2 and positive correlation with tumor necrosis factor alpha (TNF-α). Midpoint S1P levels during adjuvant therapy were lower than baseline, with near return to baseline after completion, indicating a relationship between chemotherapy and circulating S1P. While stage of disease did not correlate with plasma S1P levels, they were lower among patients with Her2-enriched and triple-negative breast cancer as compared to luminal-type breast cancer. Plasma S1P levels are paradoxically suppressed in aggressive breast cancer and during adjuvant chemotherapy, which raises the possibility that postoperative plasma S1P levels do not reflect S1P secretion from resected breast cancer.

Rationale and design of the multidisciplinary team IntervenTion in cArdio-oNcology study (TITAN)

BackgroundCancer is the leading cause of premature death in Canada. In the last decade, important gains in cancer survival have been achieved by advances in adjuvant treatment. However, many oncologic treatments also result in cardiovascular "toxicity". Furthermore, cardiac risk factors such as hypertension, dyslipidemia, and diabetes mellitus are known to contribute to the progression of cardiac damage and clinical cardiotoxicity. As such, for many survivors, the risk of death from cardiac disease exceeds that of recurrent cancer. While provision of care by multidisciplinary teams has been shown to reduce mortality and hospitalizations among heart failure patients, the effect of assessments and interventions by multidisciplinary specialists in cancer patients receiving cardiotoxic chemotherapy regimens is currently unknown. Accordingly, we will examine the effect of a multi-disciplinary team interventions in the early assessment, identification and treatment of cardiovascular risk factors in cancer patients receiving adjuvant systemic therapy. Our main hypothesis is to determine if the incidence of LV dysfunction in cancer patients undergoing adjuvant therapy can be reduced through a multidisciplinary team approach.Methods/designThis is a randomized study comparing intensive multidisciplinary team intervention to usual care in the prevention of LV remodeling in patients receiving anthracycline or trastuzumab-based chemotherapy. Main objectives include early detection strategies for cardiotoxicity using novel biomarkers that reflect myocardial injury, remodeling and/or dysfunction; early identification and intensive treatment of cardiovascular risk factors; and early intervention with supportive care strategies including nutritional and pharmacist counselling, exercise training and cardiology team support. Secondary objectives include correlation of novel biomarkers to clinical outcomes; correlation of multidisciplinary interventions to adverse clinical outcomes; relationship of multidisciplinary interventions and chemotherapy dose density; preservation of lean muscle mass; and patient reported outcomes (symptom intensity and quality of life).DiscussionCardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, TITAN will be the first randomized trial examining the utility of multidisciplinary team care in the prevention of cardiotoxicity. We expect our results to inform comprehensive and holistic care for patients at risk for negative cancer therapy mediated sequelae.Trial registrationClinicalTrials.gov, NCT01621659 Registration Date 4 June 2012.

Growth factor use and costs in breast cancer patients undergoing adjuvant therapy.

e18277Background: Myeloid growth factor support (GFs) reduces the incidence/duration of neutropenia and facilitates dose intensity. GFs is recommended by ASCO guidelines when the risk of chemothera...

Cancer-related fatigue shows a stable association with diurnal cortisol dysregulation in breast cancer patients

Fatigue is a major burden for breast cancer patients undergoing adjuvant therapy. Yet, its pathophysiology is still not well understood. Hypothesized mechanisms include dysregulations in the hypothalamic–pituitary–adrenal (HPA) axis, which may be reflected in alterations in the diurnal cortisol patterns. However, studies on the association between cortisol and fatigue during adjuvant cancer therapy are rare.We therefore assessed salivary cortisol at awakening, 0.5h post-awakening, noon, 5pm and 10pm/bedtime in 265 breast cancer patients undergoing adjuvant therapy at three timepoints. Cancer-related fatigue was assessed with the Fatigue Assessment Questionnaire (FAQ) covering the physical, affective, and cognitive fatigue dimensions. Multiple linear regression analyses were performed cross-sectionally at the three timepoints as well as longitudinally considering changes in cortisol and fatigue over time. The results showed that the physical dimension of cancer-related fatigue was significantly associated with increased evening cortisol levels and higher overall cortisol secretion. These associations were independent of depressive symptoms. Morning cortisol levels, the cortisol awakening response and the diurnal slope were not consistently associated with physical fatigue. Affective and cognitive fatigue showed no clear association with any of the cortisol parameters.In conclusion, the physical but not the affective or cognitive dimension of fatigue seems associated with cortisol dysregulations in breast cancer patients undergoing adjuvant therapy, characterized by an unaffected cortisol level in the morning but blunted decline to the evening level. Research focusing on disturbances of the cortisol rhythm and HPA dysregulations during and after cancer treatment may open new strategies to reduce cancer-related fatigue.

Nutritional and metabolic status of breast cancer women.

The nutritional and metabolic status have been related to cancer risk factors as well as to cancer treatment morbimortality. Thus, its assessment is important for developing strategies for the promotion, maintenance and / or recovery of nutritional status and cancer outcome. Several different methods for nutritional assessment in breast cancer patients undergoing adjuvant therapy were used, including subjective global assessment (SGA), body mass index (BMI), triceps skinfold (TSF), mid-arm circumference (MAC), adductor pollicis muscle thickness (APMT), hand grip strength (HGS) and bioelectrical impedance analysis (BIA). The presence of metabolic syndrome (MetS) was also evaluated. The occurrence of complications during cancer treatment versus the nutritional status was assessed. We followed 78 women with a mean age of 53.2 } 11.6 years. Most patients were considered well nourished (80.8%). Excessive body fat mass by BIA and MetS were found in 80,8 % and 41.9% of the patients respectively. There were significant differences in BMI, TSF, WC (waist circumference) and % fat mass between patients with and without MetS. Most patients experienced complications during cancer treatment, but there was no association with nutritional or metabolic status. In breast cancer women undergoing adjuvant therapy, the prevalence of metabolic syndrome was high and, on the contrary, undernutrition was low. There were no short-term effects of metabolic syndrome or undernutrition on clinical outcomes.

Cardiorespiratory fitness in breast cancer patients undergoing adjuvant therapy

Purpose. The aim of this work was to investigate cardiorespiratory fitness in breast cancer patients at different time points of anti-cancer treatment.Patients and methods. Non-metastatic breast cancer patients (n = 222, mean age 55 years) were categorized into four subgroups according to their treatment status. Cardiopulmonary exercise testing (CPET) was used to measure patients’ cardiorespiratory fitness, including oxygen delivery and metabolic muscle function. Testing was performed by bicycle ergometry, and maximal oxygen uptake (VO2peak) was measured. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of the O2 supply to muscle. Analysis of covariance was used to estimate the impact of different cancer treatments on cardiorespiratory fitness with adjustment for clinical factors.Results. Submaximal measures were successfully assessed in 220 (99%) and 200 (90%) patients for HR50 and VT, while criteria for maximal exercise testing were met by 176 patients (79%), respectively. The mean VO2peak was 20.6 ± 6.7 ml/kg/min, mean VT 10.7 ± 2.9 ml/min/kg and mean HR50 112 ± 16 beats/min. Chemotherapy was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant chemotherapy compared to patients with no chemotherapy or those who just started chemotherapy regime (all p < 0.01). Patients post adjuvant chemotherapy reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5 ± 4.8 ml/kg/min). Similarly, HR50 was significantly associated with treatment. However, VT was not associated with treatment.Conclusion. Breast cancer patients have marked and significantly impaired cardiopulmonary function during and after chemotherapy. Hereby, chemotherapy appears to impair cardiorespiratory fitness by influencing the oxygen delivery system rather than impacting metabolic muscle function. Our findings underline the need of exercise training in breast cancer patients to counteract the loss of cardiorespiratory fitness during the anti-cancer treatment.

AB1425-HPR Effects of a yoga program on pain relief, reducing anxiety and extended range of motion of knee in rheumatoid arthritis patients

BackgroundRheumatoid Arthritis as a chronic systemic disease, is the most common cause of joints inflammation and deformity. Chronic pain, fatigue, decline in physical activity and joint range of motion limitation...

Treatment of depressive symptoms in breast cancer patients undergoing adjuvant therapy.

9631 Background: Studies have shown a high prevalence of depression in patients with cancer. Women with breast cancer may have a high risk of depression particularly in a post-menopausal or estrogen deficient state and may develop a high level of depressive symptoms at the time of initial diagnosis. Newly diagnosed early stage breast cancer patients were screened for depressive symptoms prior to the initiation of adjuvant therapy. The oral antidepressant fluoxetine was studied to determine if its use affected depressive symptoms, completion of adjuvant treatment, quality of life, and survival. Methods: Patients with newly diagnosed early stage breast cancer were screened for depressive symptoms prior to the initiation of adjuvant therapy. Patients with depressive symptoms were randomized in a double blind fashion to daily oral fluoxetine (20 mg) or placebo. Patients were then followed for 6 months and evaluated for quality of life, completion of adjuvant treatment, and depressive symptoms. Patients with stage I disease at the time of initial diagnosis were subsequently assessed for disease recurrence and survival at five years. Results: Two hundred three of 357 screened patients with newly diagnosed early stage breast cancer were found to have depressive symptoms prior to the initiation of adjuvant therapy. One hundred ninety-three patients were randomized to fluoxetine or placebo. The use of fluoxetine for 6 months resulted in a significantly (p&lt;0.01) higher number of patients with an improvement in quality of life, a higher completion of adjuvant treatment (chemotherapy, hormonal therapy, chemotherapy plus hormonal therapy) and a reduction in depressive symptoms compared to patients who received placebo. At five years, there was a significant (p&lt;0.01) improvement in survival for patients with Stage I disease who received fluoxetine, possibly related to a higher completion of adjuvant treatment. Conclusions: An antidepressant should be considered for early stage breast cancer patients with depressive symptoms who are receiving adjuvant treatment.

Psychological impact of exercise in women with breast cancer receiving adjuvant therapy: What is the optimal dose needed?

9074 Background: Several meta-analyses have examined the role of exercise interventions in improving psychological outcomes in cancer survivors but most did not focus on adjuvant therapy period and did not investigate the optimal dose of exercise needed. Methods: The present meta-analysis examines the impact of exercise interventions delivered at this particular period on fatigue, anxiety, depression and quality-of-life (QoL) as well as dose-response relationships between volume of prescribed exercise and these psychological outcomes. Randomized controlled trials that proposed an exercise intervention to breast cancer patients undergoing chemotherapy and/or radiotherapy were systematically identified and coded. Standardized mean differences (SMDs) of psychological outcomes were weighted by the inverse of their variances to obtain a pooled estimate using random effects model. Linear and quadratic regressions were carried out to explore dose-response relationships. Results: In total, 17 studies involving 1380 participants and 20 exercise interventions were included. Intervention subjects significantly reduced their fatigue and depression levels showing pooled effect sizes (EF) and their associated 95% confidence interval (95%CI) of -0.28 [95%CI: -0.54; -0.03] and -0.28 [95%CI: -0.46; -0.09] respectively. Levels of anxiety also appeared to be reduced but pooled estimate did not reach significance (p=0.06). Significantly increased QoL was observed: EF=0.34 [95%CI: 0.07; 0.62] favouring intervention. Consistent and significant inverse associations of weekly and total volume of prescribed exercise were observed with fatigue (F test: p=0.04, R²=0.19 and p=0.009, R²=0.26 respectively) and QoL (F test: p=0.01, R²=0.14 and p=0.02, R²=0.29 respectively), implying that SMDs magnitude decreased as exercise dose increased. Conclusions: Exercise intervention enhanced fatigue, depression and QoL in breast cancer patients undergoing adjuvant therapy. Prescription of relatively low doses of exercise (&lt;12 MET.h per week) consisting in approximately 90-120 min of weekly moderate physical exercise seems more efficacious in improving fatigue and QoL than higher doses.

Adjuvant Therapy for completely resected Stage II Colon Cancer

Colon cancer is potentially curable by surgery. Although adjuvant chemotherapy benefits patients with stage III disease, there is uncertainty of such benefit in stage II colon cancer. A systematic review of the literature was performed to better define the potential benefits of adjuvant therapy for patients with stage II colon cancer. To determine the effects of adjuvant therapy on overall survival and disease-free survival in patients with stage II colon cancer. Ovid MEDLINE (1986-2007), EMBASE (1980-2007), and EBM Reviews - Cochrane Central Register of Controlled Trials ( to 2007) were searched using the medical headings "colonic neoplasms", "colorectal neoplasms", "adjuvant chemotherapy", "adjuvant radiotherapy" and "immunotherapy", and the text words "colon cancer" and "colonic neoplasms". In addition, proceedings from the annual meetings of the American Society of Clinical Oncology and the European Society of Medical Oncology (1996 to 2004) as well as personal files were searched for additional information. Randomized trials or meta-analyses containing data on stage II colon cancer patients undergoing adjuvant therapy versus surgery alone. :Three reviewers summarized the results of selected studies. The main outcomes of interest were overall and disease-free survival, however, data on toxicity and treatment delivery were also recorded. With regards to the effect of adjuvant therapy on stage II colon cancer, the pooled relative risk ratio for overall survival was 0.96 (95% confidence interval 0.88, 1.05). With regards to disease-free survival, the pooled relative risk ratio was 0.83 (95% confidence interval 0.75, 0.92). Although there was no improvement in overall survival in the pooled analysis, we did find that disease-free survival in patients with stage II colon cancer was significantly better with the use of adjuvant therapy. It seems reasonable to discuss the benefits of adjuvant systemic chemotherapy with those stage II patients who have high risk features, including obstruction, perforation, inadequate lymph node sampling or T4 disease. The co-morbidities and likelihood of tolerating adjuvant systemic chemotherapy should be considered as well. There exists a need to further define which high-risk features in stage II colon cancer patients should be used to select patients for adjuvant therapy. Also, researchers must continue to search for other therapies which might be more effective, shorter in duration and less toxic than those available today.

The fate of disseminated tumor cells in bone marrow of primary breast cancer patients after adjuvant systemic therapy

The presence of cytokeratin positive cells in the bone marrow of breast cancer patients has been proven to be an independent prognostic factor. Their fate in primary breast cancer patients undergoing adjuvant therapy is of particular interest. We investigated the bone marrow status of 112 patients undergoing postoperative adjuvant treatment before and after therapy. 373 patients with histologically confirmed primary breast cancer underwent bone marrow aspiration at the time of primary surgery. All patients were informed of their bone marrow status and offered repeat aspiration after 12 months. All patients were then treated with adjuvant chemotherapy, endocrine therapy or both based on current treatment recommendations. 112 patients returned for a second bond marrow aspiration after a mean interval of 12 months following the initiation of adjuvant treatment. In 93 of 112 patients (83%) disseminated tumor cells had been found in the bone marrow before initiation of systemic chemo/endocrine therapy. At the time of follow-up sampling, after surgery and completion of adjuvant chemotherapy, the positivity rate dropped to 24%. Positive bone marrow status during follow-up was only associated with grading (p=0.020). Adjuvant treatment regimens are not able to completely eliminate cytokeratin positive cells from the bone marrow. Prospective studies need to evaluate, whether these cells could become targets for additional adjuvant therapy.

Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy

The presence of cytokeratin-positive cells in the bone marrow of breast cancer patients has been proven to be an independent prognostic factor. Their fate in primary breast cancer patients undergoing adjuvant therapy is of particular interest. We investigated the bone marrow status of 112 patients undergoing postoperative adjuvant treatment before and after therapy. A total of 373 patients with histologically confirmed primary breast cancer underwent bone marrow aspiration at the time of primary surgery. All patients were informed of their bone marrow status and offered repeat aspiration after 12 months. All patients were then treated with adjuvant chemotherapy, endocrine therapy or both based on current treatment recommendations. About 112 patients returned for a second bone marrow aspiration after a mean interval of 12 months following the initiation of adjuvant treatment. In 93 of 112 patients (83%) disseminated tumor cells had been found in the bone marrow before initiation of systemic chemo/endocrine therapy. At the time of follow-up sampling, after surgery and completion of adjuvant chemotherapy, the positivity rate dropped to 24%. Positive bone marrow status during follow-up was only associated with grading (p=0.020). Adjuvant treatment regimens are not able to completely eliminate cytokeratin-positive cells from the bone marrow. Prospective studies need to evaluate, whether these cells could become targets for additional adjuvant therapy.

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-beta (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.