Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients

Some breast cancer survivors experience cognitive decline following chemotherapy. We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60). All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval. No differences in cognitive functioning between the four groups were observed at the first assessment. More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time (25% versus 6.7%; odds ratio [OR] = 5.3, 95% confidence interval [CI] = 1.3 to 21.2, P = .02). No such difference was observed for the FEC or the no-CT groups (FEC versus control: OR = 2.2, 95% CI = 0.5 to 9.1, P = .27; no-CT versus Control: OR = 2.2, 95% CI = 0.6 to 8.0; P = .21). Some cytotoxic treatment for breast cancer affects cognition in a subset of women.     

Decline in pulmonary function in patients with breast cancer receiving dose-dense chemotherapy: a prospective study

Background: Prompted by complaints of dyspnea in breast cancerpatients receiving adjuvant dose-dense chemotherapy (DDC), wesought to evaluate the possible association of DDC with pulmonarydysfunction. Patients and methods: A total of 34 consecutive patients receivingadjuvant DDC were enrolled. The chemotherapy regimen consistedof i.v. doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²(AC) every 14 days x4 with growth factor support followed byweekly i.v. paclitaxel 80 mg/m² x12. The following parameterswere prospectively measured before and after the AC protocol(P1, P2) and at completion of paclitaxel treatment (P3): presenceof dyspnea, blood pressure, pulse rate, hemoglobin, erythrocytesedimentation rate, C-reactive protein level, cardiac ejectionfraction, and pulmonary function. Repeated measures analysiswas used to evaluate differences among the time points, andpaired t-test was used to evaluate differences between consecutivetime points. Results: Although only five patients (15%) complained of dyspnea,there was a significant decrease in mean carbon monoxide diffusingcapacity (DLCO), in all patients from P1 (22.09 ml/min/mmHg)to P3 (15 ml/min/mmHg) and in 29 of 32 patients (90.6%) fromP1 to P2 (15.96 ml/min/mmHg) (P < 0.001). Conclusions: DDC is associated with a statistical significantreduction in DLCO. Awareness of this potential toxicity maybe important in women with preexisting lung disease. Key words: breast cancer, CRP pulmonary function, DLCO, dose-dense chemotherapy, ESR Received for publication August 26, 2008. Accepted for publication August 29, 2008.     

Hepatic staging in operable breast cancer: a reappraisal from a prospective study

A consecutive series of 100 patients affected by breast cancer and referred for surgical treatment were studied for the eventual spread of the tumour to the liver (echography, carcinoembryonic antigen [CEA], hepatic enzymes). Hepatic echography was positive in five cases: two also had bone and skin metastases at the time of diagnosis, and one was a case of remastectomy (these three patients died rather quickly of the disease); the remaining two patients are free of the disease 24 months after surgery and thus should be considered false-positive cases. Hepatic enzymes were not significant. The same was true for CEA except in nine cases with levels much greater than 20 ng/ml (six of these had early local and/or distant metastases). It is concluded that the usefulness of routine hepatic echography before locoregional treatment of breast cancer is rather limited. CEA much greater than 20 ng/ml may be useful prognostically.     

Chemotherapy-induced nausea and vomiting in breast cancer patients: a prospective observational study

Despite advances in the prevention and treatment of emesis, nausea and vomiting are still considered by patients to be among the most severe and feared adverse effects of chemotherapy for breast cancer. There is, however, a paucity of prospective data documenting the prevalence and severity of emesis in patients with breast cancer in the era of modern antiemetics.This prospective multicenter study evaluated chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer. Patients were given a daily diary to record the frequency and severity of nausea and vomiting during the first 5 days following chemotherapy. Data were collected until either the cessation of chemotherapy or the administration of a maximum of 6 cycles of treatment. Data are available from 143 patients who received a total of 766 cycles of chemotherapy. Prevalence rates of any nausea or any vomiting were, respectively, 37% and 13% at 24 hours and 70% and 15% during days 2-5. Severe emesis was reported by fewer than 10% of patients. Risk factors associated with CINV included age younger than 40 years, nausea expectation, not eating before treatment, and low alcohol use. The prevalence of severe CINV for breast cancer was relatively low compared with the prevalence reported in the literature. As a result of the observational design of this study, the results may better reflect the "true" prevalence of nausea and vomiting than do estimates from previously reported randomized controlled trials. Several patient characteristics that predict which patients are at increased risk of developing severe symptoms were identified.     

Risk factors for breast cancer in Iran: a case-control study

Background  

Iranian breast cancer patients are relatively younger than their Western counterparts. The objective of the present study was to investigate risk factors for breast cancer in Iranian women.     

Prognostic significance of biologic markers in node-negative breast cancer patients: a prospective study

It is generally thought that future advances in the treatment and cure of breast cancer patients will be made possible through a deeper understanding of tumor biology and an improved capability to define the prognosis of each single patient. This will lead to the formulation of new, more selective, and patient-tailored therapies. It is therefore important, when studying potential prognostic factors, to follow methodologic requirements and guidelines which involve the carrying out of prospective studies as confirmatory steps. Repeatedly or recently investigated prognostic markers (tumor size, menopausal status, ER, PgR, ³H thymidine labeling index, c-erbB-2 and p27 expression) were evaluated on a series of 286 prospectively recruited node negative breast cancer patients who underwent loco-regional treatment alone and were closely followed. The individual and relative prognostic contribution of each variable with respect to other factors, as well as their ability to identify node negative patients at risk, were assessed by univariate and multivariate analysis. At a five-year follow-up, only tumor size (p=0.021) and TLI (p=0.016) individually proved to be significant prognostic indicators of relapse-free survival. Conversely, p27 expression was not related to RFS and c-erbB-2 expression appeared to have only a short-term effect on patient prognosis. TLI and tumor size, tested in multivariate analysis along with ER and menopausal status, maintained their independent prognostic relevance. The study, performed on a large series of node-negative patients given loco-regional treatment alone, for the first time prospectively recruited, showed the prognostic relevance of TLI and its independence from other clinico-pathologic and biologic factors over a five-year period.     

Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study

BackgroundBreast cancer brain metastases (BCBM) are challenging complications that respond poorly to systemic therapy. The role of the blood–tumor barrier in limiting BCBM drug delivery and efficacy has been debated. Herein, we determined tissue and serum levels of capecitabine, its prodrug metabolites, and lapatinib in women with BCBM resected via medically indicated craniotomy.MethodsStudy patients with BCBM requiring surgical resection received either single-dose capecitabine (1250 mg/m²) 2–3 h before surgery or 2–5 doses of lapatinib (1250 mg) daily, the last dose 2–3 h before surgery. Serum samples were collected serially on the day of surgery. Drug concentrations were determined in serum and BCBM using liquid chromatography tandem mass spectrometry.ResultsTwelve patients were enrolled: 8 for capecitabine and 4 for lapatinib. Measurable drug levels of capecitabine and metabolites, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine, and 5-fluorouracil, were detected in all BCBM. The ratio of BCBM to serum was higher for 5-fluorouracil than for capecitabine. As for lapatinib, the median BCBM concentrations ranged from 1.0 to 6.5 µM. A high variability (0.19–9.8) was noted for lapatinib BCBM-to-serum ratio.ConclusionsThis is the first study to demonstrate that capecitabine and lapatinib penetrate to a significant though variable degree in human BCBM. Drug delivery to BCBM is variable and in many cases appears partially limiting. Elucidating mechanisms that limit drug concentration and innovative approaches to overcome limited drug uptake will be important to improve clinical efficacy of these agents in the central nervous system.Trial registration ID: {"type":"clinical-trial","attrs":{"text":"NCT00795678","term_id":"NCT00795678"}}NCT00795678.     

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients. Participants and Methods: Post‐menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression‐based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone. Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected. Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.     

Qualitative and quantitative dermatoglyphic traits in patients with breast cancer: a prospective clinical study

Background  

Breast cancer is one of the most extensively studied cancers and its genetic basis is well established. Dermatoglyphic traits are formed under genetic control early in development but may be affected by environmental factors during first trimester of pregnancy. They however do not change significantly thereafter, thus maintaining stability not greatly affected by age. These patterns may represent the genetic make up of an individual and therefore his/her predisposition to certain diseases. Patterns of dermatoglyphics have been studied in various congenital disorders like Down's syndrome and Kleinfelter syndrome. The prints can thus represent a non-invasive anatomical marker of breast cancer risk and thus facilitate early detection and treatment.     

Sexual dysfunction in treated breast cancer patients

Background: This study examined the impact of breast cancer therapyon women's sexuality.Patients and methods: A questionnaire concerning various sexualproblems experienced before and after treatment was anonymously completed by50 women in the outpatient clinic of our hospital's Division of RadiationOncology. To be eligible, subjects had to be disease-free and sexually active.They also had to have undergone surgery at least one year previously and havecompleted CT and/or RT. Fifty-eight percent of the women involved hadundergone mastectomy and 42% had undergone quadrantectomy followed byRT.Results: Ninety percent of the subjects continued sexual activityafter treatment, but there was an increase in the incidence of sexual problemswhich resulted in a slight reduction in the quality of their sex lives.Sixty-four percent of the women experienced an absence of sexual desire and48% low sexual desire, while 38% had dyspareunia, 44%frigidity and 42% lubrication problems. Vaginismus, brief intercourseand female orgasmic disorder were reported by 30% of the subjects.Thirty-six percent suffered from sexual dysfunction before treatment, whichworsened in about 27%, while in 49% of women sexual problemsarose mainly after chemotherapy (26%) or surgery (12%). Aboutone-half experienced changes in the relationship with their partner.Conclusion: Breast cancer patients experienced sexual dysfunction;ours found it easier to discuss the problems with their partner during theirillness (62%) than with doctors and psychologists (15%).     

Sleep duration and breast cancer: a prospective cohort study

Breast cancer incidence has increased during recent decades for reasons that are only partly understood. Prevalence of sleeping difficulties and sleepiness has increased, whereas sleeping duration per night has decreased. We hypothesized that there is an inverse association between sleep duration and breast cancer risk, possibly due to greater overall melatonin production in longer sleepers. This population-based study includes information from women born in Finland before 1958. Sleep duration, other sleep variables, and breast cancer risk factors were assessed by self-administered questionnaires given in 1975 and in 1981. Breast cancer incidence data for 1976 to 1996 was obtained from the Finnish Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from Cox proportional hazards models adjusting for potential confounders. Altogether, 242 cases of breast cancer occurred over the study period among the 12,222 women with sleep duration data in 1975. For these women, the HRs for breast cancer in the short (< or =6 hours), average (7-8 hours), and long sleep (> or =9 hours) duration groups were 0.85 (CI, 0.54-1.34), 1.0 (referent), and 0.69 (CI, 0.45-1.06), respectively. Analysis restricted to the 7,396 women (146 cases) whose sleep duration in 1975 and 1981 were in the same duration group (stable sleepers) yielded HRs of 1.10 (CI, 0.59-2.05), 1.0, and 0.28 (CI, 0.09-0.88), with a decreasing trend (P = 0.03). This study provides some support for a decreased risk of breast cancer in long sleepers.     

Risk for endometrial cancer following breast cancer: a prospective study in Sweden

The risk for endometrial cancer among women with breast cancer might increase following use of tamoxifen, recently classified as a carcinogen of the human endometrium. However, the strength of the association remains uncertain and it is unknown whether use of this drug - widely prescribed in Sweden since the mid-1980s - has had any measurable effect at the population level. We analyzed all cases of breast cancer (n = 131,614) detected in the nationwide Swedish Cancer Registry in 1958-93. Incident cases of endometrial cancer during follow-up were identified also through the Cancer Registry. Standardized incidence ratios (SIR) and their 95 percent confidence intervals(CI) were computed by use of nationwide rates of endometrial cancer, adjusted for age and calendar year. During follow-up of up to 35 years of the breast cancer cohort, 803 incident endometrial cancers were identified, yielding an overall SIR of 1.58 (CI = 1.47-1.70). In univariate analyses, there was no increase in SIR in recent years. However, the excess risk increased linearly with increasing age at breast cancer diagnosis (P trend < 0.0001) and decreased markedly with longer follow-up (P trend < 0.0001). A multivariate regression analysis, with adjustment for age and year of follow-up, revealed no increased risk for subsequent endometrial cancer among breast cancer cases diagnosed more recently (P trend = 0.19); compared with the period 1958-63,the risk estimate in the last time period (1989-93) was 0.72 (CI =0.51-1.01). We conclude that the risk for endometrial cancer following breast cancer has not increased over time in Sweden. This revised version was published online in July 2006 with corrections to the Cover Date.     

Changes in pulmonary function after incidental lung irradiation for breast cancer: A prospective study

PURPOSE: The aim of this study was to analyze changes in pulmonary function after radiation therapy (RT) for breast cancer. METHODS AND MATERIALS: A total of 39 consecutive eligible women, who underwent postoperative irradiation for breast cancer, were entered in the study. Spirometry consisting of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), carbon monoxide diffusing capacity (DLCO), and gammagraphic (ventilation and perfusion) pulmonary function tests (PFT) were performed before RT and 6, 12, and 36 months afterwards. Dose-volume and perfusion-weighted parameters were obtained from 3D dose planning: Percentage of lung volume receiving more than a threshold dose (Vi) and between 2 dose levels (V(i-j)). The impact of clinical and dosimetric parameters on PFT changes (Delta PFT) after RT was evaluated by Pearson correlation coefficients and stepwise lineal regression analysis. RESULTS: No significant differences on mean PFT basal values (before RT) with respect to age, smoking, or previous chemotherapy (CT) were found. All the PFT decreased at 6 to 12 months. Furthermore FVC, FEV(1), and ventilation recovered almost to their previous values, whereas DLCO and perfusion continued to decrease until 36 months (-3.3% and -6.6%, respectively). Perfusion-weighted and interval-scaled dose-volume parameters (pV(i-j)) showed better correlation with Delta PFT (only Delta perfusion reached statistically significance at 36 months). Multivariate analysis showed a significant relation between pV(10-20) and Delta perfusion at 3 years, with a multiple correlation coefficient of 0.48. There were no significant differences related to age, previous chemotherapy, concurrent tamoxifen and smoking, although a tendency toward more perfusion reduction in older and nonsmoker patients was seen. CONCLUSIONS: Changes in FVC, FEV1 and ventilation were reversible, but not the perfusion and DLCO. We have not found a conclusive mathematical predictive model, provided that the best model only explained 48% of the variability. We suggest the use of dose-perfused volume and interval-scaled parameters (i.e., pV(10-20)) for further studies.     

Energy balance and breast cancer risk: a prospective cohort study

Summary While there is evidence that breast cancer risk is positively associated with body mass index (in postmenopausal women) and energy intake and inversely associated with physical activity, few studies have examined breast cancer risk in association with energy balance, the balance between energy intake and expenditure. Therefore, in the cohort study reported here, we studied the independent and combined associations of vigorous physical activity, energy consumption, and body mass index (BMI), with breast cancer risk. The investigation was conducted in 49,613 Canadian women who were participants in the National Breast Screening Study (NBSS) and who completed self-administered lifestyle and food frequency questionnaires between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000. During a mean 16.4 years of follow-up, we observed 2545 incident breast cancer cases. Due to exclusions for various reasons, the analyses were based on 40,318 subjects amongst whom there were 1673 incident cases of breast cancer. Participation in vigorous physical activity and body mass index were not independently associated with breast cancer risk in the total cohort. A statistically significant positive trend was observed, however, between energy intake and breast cancer risk (P _trend = 0.01). Although there was some variation in risk associated with vigorous physical activity, and BMI when the analyses were stratified by menopausal status, these interactions were not statistically significant. The interaction between menopausal status and energy intake, however, was of borderline statistical significance (P _interaction = 0.06), with a statistically significant increased risk of breast cancer associated with highest versus lowest quartile of energy intake among premenopausal women (Hazard Ratio [HR] = 1.45, 95% confidence interval [CI] = 1.13– 1.85, P _trend = 0.001). There was evidence of an increased risk of breast cancer associated with a relatively high body mass index among postmenopausal women in the highest quartile level of energy intake (Hazard Ratio [HR] = 1.72, 95% confidence interval [CI] = 1.01– 2.93, P _trend = 0.05). In addition, there was evidence of an increased risk of breast cancer among premenopausal, physically inactive, overweight/obese women who consumed ≥1972 kcal/day compared to physically active normal weight women who consumed <1972 kcal/day (HR = 1.60, 95% CI = 1.08–2.37). Our data suggest that obese premenopausal women with relatively high energy intake may be at increased risk of breast cancer. In addition, energy imbalance, represented by a relatively high energy intake, lack of participation in vigorous physical activity, and a relatively high body mass index, may be associated with increased breast cancer risk, particularly among premenopausal women.     

Pulmonary sequelae of treatment for breast cancer: a prospective study

PURPOSE: To prospectively study the effects of loco-regional radiotherapy in women with breast cancer. METHODS AND MATERIALS: Thirty consecutive patients with breast resection underwent clinical, lung function, radiographic, and thoracic high-resolution computed tomography evaluation before and at 1, 3, 6, and 12 months after adjuvant radiotherapy. Chemotherapy was also administered to 15 patients. RESULTS: Nineteen patients reported mild respiratory symptoms at 1 month, which resolved completely at 6 months after radiotherapy. Opacities were present on 80% of chest radiographs and in all patients on high-resolution computed tomography by 3 months. These opacities became compact and persisted on high-resolution computed tomography at 12 months. Lung function indices, including FEV1, FVC, TLC, and DLCO, progressively declined after radiotherapy, and was irreversible at 12 months (p < 0.05). Patients who received chemotherapy did not have significantly different lung function indices compared with their counterparts at all time points (p > 0.05). CONCLUSIONS: Our results have shown that adjuvant loco-regional radiotherapy, a common practice in breast cancer treatment, is associated with irreversible reduction in lung function parameters. These changes are accompanied by radiological evidence of persistent lung injury. Further studies should be performed to evaluate the incidence and long-term pulmonary sequelae of current treatment for breast cancer.     

Urinary androgens and breast cancer risk: results from a long-term prospective study based in Guernsey

Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1887 of the urine specimens. In 1971 we reported that subnormal amounts of urinary A and E were associated with a significantly increased risk of breast cancer. The cohort has been followed regularly during the 37 years since inception of the study and, by May 1998, 248 women had been diagnosed with breast cancer. Urinary androgen metabolites had been measured in 116 of these cases. Analysis of these data confirmed that women diagnosed in the first decade of the study were more likely to have low levels of urinary androgen metabolites. In the following decades, however, those who developed breast cancer were more likely to have manifested an increased A and E excretion. The reversal in the relationship between androgen metabolite excretion and risk suggests that age, or probably more importantly, menopausal status at diagnosis is an important modifying factor. Dichotomizing at age 50 it was found that in the younger age group (predominantly premenopausal) the rate ratios in the lowest tertile of A or E excretion were two- to threefold greater than for those in the highest tertile (chi2(1) = 3.57; P = 0.06: chi2(1) = 4.70; P = 0.03 for A and E respectively). In contrast, in the older age group comprising predominantly post-menopausal women, the rate ratios associated with the lowest tertile of A or E were half that of those in the highest tertile (chi2(1) = 4.10; P = 0.04; chi2(1) = 8.72; P = 0.003 for A and E respectively). This suggests that there may be different endocrine promotional factors for pre-and post-menopausal breast cancer. Hormonal risk factors may vary during the lifetime of an individual woman and this may have profound consequences for prevention strategies.