The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder: a national Swedish study.

PURPOSE: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD. METHODS: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms. RESULTS: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters. CONCLUSIONS: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons' vs. daughters' risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements.

All-cause and cardiovascular mortality risk after surgery versus radioiodine treatment for hyperthyroidism.

BACKGROUND: Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women. METHODS: Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery between 1976 and 2000. Comparisons between treatments were made to assess all-cause and cause-specific deaths to 2013. Three different statistical methods were applied: Cox regression, propensity score matching and inverse probability weighting. RESULTS: Of the 10 992 patients included, 10 250 had been treated with radioiodine (mean age 65·1 years; 8668 women, 84·6 per cent) and 742 had been treated surgically (mean age 44·1 years; 633 women, 85·3 per cent). Mean duration of follow-up varied between 16·3 and 22·3 years, depending on the statistical method used. All-cause mortality was significantly lower among surgically treated patients, with a hazard ratio of 0·82 in the regression analysis, 0·80 in propensity score matching and 0·85 in inverse probability weighting. This was due mainly to lower cardiovascular mortality in the surgical group. Men in particular seemed to benefit from surgery compared with radioiodine treatment. CONCLUSION: Compared with treatment with radioiodine, surgery for hyperthyroidism is associated with a lower risk of all-cause and cardiovascular mortality in the long term. This finding was more evident among men.

The role of marriage in criminal recidivism: a longitudinal and co-relative analysis.

AIMS: Marriage is associated with a reduced rate of criminal recidivism, but the underlying mechanisms have only partly been elucidated. We seek to clarify the nature of the association between marriage and recidivism and how that relationship may be moderated as a function of gender, deviance of spouse, a history of violence and familial risk. METHOD: We utilise a longitudinal cohort design consisting of Swedish men (n = 239 328) and women (n = 72 280), born between 1958 and 1986, who were convicted of at least one crime before age 20 and were not married prior to age 20. The analyses used Cox regression with marriage as a time-dependent covariate. We also perform co-relative analyses in sibling and first cousin pairs. RESULTS: Marriage after a first crime substantially reduces risk of recidivism in both males (hazard ratio (HR) with key covariates and 95% confidence intervals 0.55, 0.53-0.57) and females (HR = 0.38, 0.34-0.42), although the effect is stronger in females. Marriage to a deviant spouse increases recidivism rates in males. In males, a history of violent criminality and high familial risk, respectively, decrease and increase sensitivity to the protective effect of marriage on recidivism. Consistent with a causal effect of marriage on recidivism, marriage was associated with a decline in risk for criminal relapse comparable with that in the population in both male-male sibling pairs (raw HR = 0.53, 0.45-0.62) and cousin pairs (HR = 0.55, 0.47, 0.65) concordant for prior convictions. CONCLUSIONS: The protective effect of marriage on risk for criminal recidivism is likely largely causal and is of importance in both males and females. Those at high familial risk for criminal behaviour are more sensitive to the protective effects of marriage.

Psychological strength assessed in late adolescence and risk for criminal behavior: a Swedish prospective cohort and twin analysis.

BACKGROUND: Certain personality traits predispose to criminal behavior (CB). We further clarify this relationship in a Swedish national sample. METHOD: Psychological strength (PS) was assessed on a nine-point scale at personal interview in 1 653 721 Swedish men aged 18-20 years. We examined the association between PS and total, violent and recurrent CB over the lifetime (logistic regression), prospectively (Cox regression) and by bivariate Cholesky decomposition in 2507 monozygotic and 2244 dizygotic twin pairs (OpenMx). RESULTS: Examining linear effects by logistic regression, PS was robustly associated with lifetime risk of total CB (per point, odds ratio = 0.74) and even more strongly associated with risk for violent (0.69) and recurrent CB (0.52). Prospective predictions of these three forms of CB by PS were similar, with hazard ratios of 0.80, 0.73 and 0.54, respectively. Twin modeling demonstrated that, for all three CB types, the association with PS arose almost entirely from familial effects. Common shared environment accounted for 72, 56 and 43% of the phenotypic correlation between PS and, respectively, total, violent and recurrent CB. Parallel figures for common genetic effects were for 24, 37 and 54%, respectively. CONCLUSIONS: PS is strongly related to risk for total CB, and even more strongly for violent and, especially, recurrent CB. This association is probably not causal but rather results from shared familial risk factors that make an impact both on PS and risk for CB. PS has a stronger overall correlation with more severe criminal outcomes and a higher proportion of that correlation results from common genetic factors.

A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

BACKGROUND: We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. METHOD: In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. RESULTS: For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. CONCLUSIONS: The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

The etiologic role of genetic and environmental factors in criminal behavior as determined from full- and half-sibling pairs: an evaluation of the validity of the twin method.

BACKGROUND: Twin studies have shown that criminal behavior (CB) is influenced by both genetic and shared environmental factors. Could these results be replicated using full-siblings and half-siblings? METHOD: In 911 009 full-siblings reared together (FSRT), 41 872 half-siblings reared together (HSRT) and 52 590 half-siblings reared apart (HSRA), CB was assessed from the Swedish Crime Register. Modeling, including testing for age differences and rearing status, was performed using the OpenMx package. RESULTS: Five sibling models were fitted examining FSRT and HSRT 0-2 years different in age, and both FSRT and HSRT, and FSRT, HSRT and HSRA 0-10 years different in age with and without a specified shared environment indexing age differences. Heritability estimates for CB ranged from 33 to 55% in females and 39 to 56% in males, similar to those found in our prior twin study on the same population. Estimates for the shared environment varied from 1 to 14% in females and 10 to 23% in males, lower than those estimated in the twin study. The specified shared environment indexed by sibling age differences was significant in all models tested. CONCLUSIONS: Heritability estimates for CB from full- and half-siblings closely approximated those found from twins in the same population, validating the twin method. Shared environmental estimates were lower, suggesting the presence of shared environmental factors for CB specific to twins. When rearing status can be assessed, full- and half-siblings offer an additional method for assessing the role of genetic and environmental factors in complex disorders. However, age differences in siblings may need to be included in the models.

Environmental transmission of violent criminal behavior in siblings: a Swedish national study.

UNLABELLED: BACKGROUND. Violent criminal behaviour (VCB) runs strongly in families partly because of shared environmental factors. Can we clarify the environmental processes that contribute to similarity of risk for VCB in siblings? METHOD: We assessed VCB from the Swedish National Crime Register for the years 1973-2011 in siblings born 1950-1991. We examined by conditional logistic and Cox proportional hazard regression, respectively, whether resemblance for VCB in sibling pairs was influenced by their age difference and whether VCB was more strongly 'transmitted' from older→younger versus younger→older siblings. RESULTS: In our best-fit logistic model, for each year of age difference in full sibling pairs, the risk for VCB in the sibling of a case versus control proband declined by 2.6% [95% confidence interval (CI) 2.2-3.0]. In our best-fit Cox model, the hazard rate for VCB in a sibling when the affected proband was older versus younger was 1.4, 2.1 and 2.9 respectively for a 1-, 5- and 10-year difference in siblings. CONCLUSIONS: Controlling for genetic effects by examining only full siblings, sibling resemblance for risk for VCB was significantly greater in pairs closer versus more distant in age. Older siblings more strongly transmitted risk for VCB to their younger siblings than vice versa. These results strongly support the importance of familial-environmental influences on VCB and provide some insight into the possible mechanisms at work.

The influence of comorbidity on mortality in ovarian cancer patients.

BACKGROUND: Ovarian cancer is a severe disease with a peak incidence in the older age groups where concurrent morbidity is common and could potentially influence mortality rates. OBJECTIVES: The aim was to study the influence of common comorbidity diagnoses on mortality in ovarian cancer patients. METHODS: The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11.139) identified in the national Cancer Register. Comorbidity data was obtained from the Patient Register and mortality from Cause of Death Register. Mortality was analyzed with Cox' proportional hazards models and subgroup analyses were performed by age and tumor histology. RESULTS: Almost all of the assessed comorbidities increased mortality in ovarian cancer patients. Thromboembolism was the most hazardous comorbidity (HR=1.95, <1 year after cancer diagnosis and HR=7.83, 1-5 years after cancer diagnosis) followed by hematologic complications (HR=1.84 and 7.11 respectively) and infectious disease (HR=1.48 and 5.28 respectively). The occurrence of diabetes mellitus and hypertension had less impact on mortality. CONCLUSION: Thromboembolism, hematologic complications and infections had a pronounced effect on mortality rates in women with ovarian cancer. The impact of comorbidity was mainly apparent among those with a more prosperous prognosis, such as longer time since cancer diagnosis, less aggressive tumors and younger age.

A Swedish national adoption study of criminality.

BACKGROUND: To clarify the role of genetic and environmental factors in criminal behavior (CB), we examined all CB and violent and non-violent subtypes (VCB and NVCB, respectively) in a Swedish national sample of adoptees and their relatives. METHOD: CB was defined by a conviction in the Swedish Crime Register with standard definitions for VCB and NVCB subtypes. We examined adoptees born 1950-1991 (n = 18 070) and their biological (n = 79 206) and adoptive (n = 47 311) relatives. RESULTS: The risk for all CB was significantly elevated in the adopted-away offspring of biological parents of which at least one had CB [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.4-1.6] and in the biological full and half-siblings of CB adoptees (OR 1.4, 95% CI 1.2-1.6 and OR 1.3, 95% CI 1.2-1.3, respectively). A genetic risk index (including biological parental/sibling history of CB and alcohol abuse) and an environmental risk index (including adoptive parental and sibling CB and a history of adoptive parental divorce, death, and medical illness) both strongly predicted probability of CB. These genetic and environmental risk indices acted additively on adoptee risk for CB. Moderate specificity was seen in the transmission of genetic risk for VCB and NVCB between biological parents and siblings and adoptees. CONCLUSIONS: CB is etiologically complex and influenced by a range of genetic risk factors including a specific liability to CB and a vulnerability to broader externalizing behaviors, and by features of the adoptive environment including parental CB, divorce and death. Genetic risk factors for VCB and NVCB may be at least partially distinct.

Evaluation of prevalent and incident ovarian cancer co-morbidity.

BACKGROUND: The peak in incidence of ovarian cancer occurs around 65 years and concurrent increasing risk by age for a number of diseases strongly influence treatment and prognosis. The aim was to explore prevalence and incidence of co-morbidity in ovarian cancer patients compared with the general population. METHODS: The study population was patients with ovarian cancer in Sweden 1993-2006 (n=11 139) and five controls per case (n=55 687). Co-morbidity from 1987 to 2006 was obtained from the Swedish Patient Register. Prevalent data were analysed with logistic regression and incident data with Cox proportional hazards models. RESULTS: Women developing ovarian cancer did not have higher overall morbidity than other women earlier than 3 months preceding cancer diagnosis. However, at time of diagnosis 11 of 13 prevalent diagnosis groups were more common among ovarian cancer patients compared with controls. The incidence of many common diagnoses was increased several years following the ovarian cancer and the most common diagnoses during the follow-up period were thromboembolism, haematologic and gastrointestinal complications. CONCLUSION: Women developing ovarian cancer do not have higher overall morbidity the years preceding cancer diagnosis. The incidence of many common diagnoses was increased several years following the ovarian cancer. It is crucial to consider time between co-morbidity and cancer diagnosis to understand and interpret associations.

Determinants of mobile phone output power in a multinational study: implications for exposure assessment.

OBJECTIVES: The output power of a mobile phone is directly related to its radiofrequency (RF) electromagnetic field strength, and may theoretically vary substantially in different networks and phone use circumstances due to power control technologies. To improve indices of RF exposure for epidemiological studies, we assessed determinants of mobile phone output power in a multinational study. METHODS: More than 500 volunteers in 12 countries used Global System for Mobile communications software-modified phones (GSM SMPs) for approximately 1 month each. The SMPs recorded date, time, and duration of each call, and the frequency band and output power at fixed sampling intervals throughout each call. Questionnaires provided information on the typical circumstances of an individual's phone use. Linear regression models were used to analyse the influence of possible explanatory variables on the average output power and the percentage call time at maximum power for each call. RESULTS: Measurements of over 60,000 phone calls showed that the average output power was approximately 50% of the maximum, and that output power varied by a factor of up to 2 to 3 between study centres and network operators. Maximum power was used during a considerable proportion of call time (39% on average). Output power decreased with increasing call duration, but showed little variation in relation to reported frequency of use while in a moving vehicle or inside buildings. Higher output powers for rural compared with urban use of the SMP were observed principally in Sweden where the study covered very sparsely populated areas. CONCLUSIONS: Average power levels are substantially higher than the minimum levels theoretically achievable in GSM networks. Exposure indices could be improved by accounting for average power levels of different telecommunications systems. There appears to be little value in gathering information on circumstances of phone use other than use in very sparsely populated regions.

Meningioma and mobile phone use--a collaborative case-control study in five North European countries.

BACKGROUND: Use of mobile telephones has been suggested as a possible risk factor for intracranial tumours. To evaluate the effect of mobile phones on risk of meningioma, we carried out an international, collaborative case-control study of 1209 meningioma cases and 3299 population-based controls. METHODS: Population-based cases were identified, mostly from hospitals, and controls from national population registers and general practitioners' patient lists. Detailed history of mobile phone use was obtained by personal interview. Regular mobile phone use (at least once a week for at least 6 months), duration of use, cumulative number and hours of use, and several other indicators of mobile phone use were assessed in relation to meningioma risk using conditional logistic regression with strata defined by age, sex, country and region. RESULTS: Risk of meningioma among regular users of mobile phones was apparently lower than among never or non-regular users (odds ratio, OR = 0.76, 95% confidence interval, CI 0.65, 0.89). The risk was not increased in relation to years since first use, lifetime years of use, cumulative hours of use or cumulative number of calls. The findings were similar regardless of telephone network type (analogue/digital), age or sex. CONCLUSIONS: Our results do not provide support for an association between mobile phone use and risk of meningioma.

Medical history, cigarette smoking and risk of acoustic neuroma: an international case-control study.

Acoustic neuroma (vestibular schwannoma) is a benign tumor of the vestibulocochlear nerve. Its recorded incidence is increasing but risk factors for this tumor have scarcely been investigated. We conducted a population-based case-control study of risk factors for acoustic neuroma in the UK and Nordic countries, including 563 cases and 2,703 controls. Tumor risk was analyzed in relation to medical history and cigarette smoking. Risk of acoustic neuroma was significantly raised in parous compared with nulliparous women (OR = 1.7, 95% CI: 1.1-2.6), but was not related to age at first birth or number of children. Risk was not associated with a history of allergic disease, past head injury, past diagnosis of a neoplasm or birth characteristics, but was significantly raised for past diagnosis of epilepsy (OR = 2.5, 95% CI: 1.3-4.9). Tumor risk was significantly reduced in subjects who had ever regularly smoked cigarettes (OR = 0.7, 95% CI: 0.6-0.9), but the reduction applied only to current smokers (OR = 0.5, 95% CI: 0.4-0.6), not ex-smokers (OR = 1.0, 95% CI: 0.8-1.3). The reduced risk of acoustic neuroma in smokers and raised risk in parous women might relate to sex hormone levels, or smoking might suppress tumor growth, but effects of parity and smoking on timing of diagnosis of the tumor are also a potential explanation. The raised risk in relation to past diagnosis of epilepsy might be a surveillance artefact or imply that epilepsy and/or antiepileptic medication use predispose to acoustic neuroma. These findings need replication by other studies and possible mechanisms need to be clarified.

Validation of short term recall of mobile phone use for the Interphone study.

AIM: To validate short term recall of mobile phone use within Interphone, an international collaborative case control study of tumours of the brain, acoustic nerve, and salivary glands related to mobile telephone use. METHODS: Mobile phone use of 672 volunteers in 11 countries was recorded by operators or through the use of software modified phones, and compared to use recalled six months later using the Interphone study questionnaire. Agreement between recalled and actual phone use was analysed using both categorical and continuous measures of number and duration of phone calls. RESULTS: Correlations between recalled and actual phone use were moderate to high (ranging from 0.5 to 0.8 across countries) and of the same order for number and duration of calls. The kappa statistic demonstrated fair to moderate agreement for both number and duration of calls (weighted kappa ranging from 0.20 to 0.60 across countries). On average, subjects underestimated the number of calls per month (geometric mean ratio of recalled to actual = 0.92, 95% CI 0.85 to 0.99), whereas duration of calls was overestimated (geometric mean ratio = 1.42, 95% CI 1.29 to 1.56). The ratio of recalled to actual use increased with level of use, showing underestimation in light users and overestimation in heavy users. There was substantial heterogeneity in this ratio between countries. Inter-individual variation was also large, and increased with level of use. CONCLUSIONS: Volunteer subjects recalled their recent phone use with moderate systematic error and substantial random error. This large random error can be expected to reduce the power of the Interphone study to detect an increase in risk of brain, acoustic nerve, and parotid gland tumours with increasing mobile phone use, if one exists.

Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries.

There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case-control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7-1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR = 1.8, 95% CI: 1.1-3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out.

Output power levels from mobile phones in different geographical areas; implications for exposure assessment.

BACKGROUND: The power level used by the mobile phone is one of the most important factors determining the intensity of the radiofrequency exposure during a call. Mobile phone calls made in areas where base stations are densely situated (normally urban areas) should theoretically on average use lower output power levels than mobile phone calls made in areas with larger distances between base stations (rural areas). AIMS: To analyse the distribution of power levels from mobile phones in four geographical areas with different population densities. METHODS: The output power for all mobile phone calls managed by the GSM operator Telia Mobile was recorded during one week in four defined areas (rural, small urban, suburban, and city area) in Sweden. The recording included output power for the 900 MHz and the 1800 MHz frequency band. RESULTS: In the rural area, the highest power level was used about 50% of the time, while the lowest power was used only 3% of the time. The corresponding numbers for the city area were approximately 25% and 22%. The output power distribution in all defined urban areas was similar. CONCLUSION: In rural areas where base stations are sparse, the output power level used by mobile phones are on average considerably higher than in more densely populated areas. A quantitative assessment of individual exposure to radiofrequency fields is important for epidemiological studies of possible health effects for many reasons. Degree of urbanisation may be an important parameter to consider in the assessment of radiofrequency exposure from mobile phone use.

Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter.

The ADH3 gene encodes alcohol dehydrogenase 3 (ADH3)/glutathione-dependent formaldehyde dehydrogenase, the ancestral and most conserved form of alcohol dehydrogenase. ADH3 is expressed in all tissues examined and the enzyme is essential for formaldehyde scavenging. We have screened the promoter region including exon 1 and exons 5, 6 and 7 of the ADH3 gene for allelic variants. Using 80 samples of genomic DNA from Swedes as template, the various parts of the gene were PCR amplified and subsequently analyzed on single strand conformation polymorphism (SSCP) gels. No abnormal migration patterns could be detected by SSCP analysis of exons 5, 6 and 7 while for the promoter region, a large number of the samples displayed differences in SSCP gel migration patterns. Cloning and sequence analysis revealed four possible base pair exchanges in the promoter region. Two transitions were found at position -197 and -196, GG --> AA, one at position -79, G --> A and finally, close to the transcription start site, a fourth transition was found at position +9, C --> T. An allele specific PCR method was developed and allele frequencies were determined in three populations: Chinese, Spanish and Swedish. GG-197,-196 and AA-197,-196 alleles were common in all three populations, G-79 and A-79 were common in Swedes and Spaniards but only A-79 was found among Chinese. T+9 was the most rare allele with an allele frequency of 1.5% in Swedes. Finally, promoter activity assessments and electrophoretic mobility shift assays demonstrated that the C+9 --> T+9 exchange resulted in a significant transcriptional decrease in HeLa cells and a decreased binding of nuclear proteins. These base pair exchanges may have an effect on the expression of the enzyme and thereby influence the capacity of certain individuals to metabolize formaldehyde.

Quality of life in patients with metastatic breast cancer receiving either docetaxel or sequential methotrexate and 5-fluorouracil. A multicentre randomised phase III trial by the Scandinavian breast group.

The purpose of this study was to evaluate the effects of two alternative chemotherapy regimes on the quality of life (QoL) of patients with advanced breast cancer. In a multicentre trial, 283 patients were randomised to receive either docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). QoL was assessed at baseline and before each treatment using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Initial compliance in the QoL study was 96% and the overall compliance 82%. QoL data were available for 245 patients (T 130 and 115 MF). Both treatment groups showed some improvement in emotional functioning during treatment, with a significant difference favouring the MF group at treatment cycles 5 and 6. In the T group, the scores on the other functional scales remained stable throughout the first six cycles. There were significant differences favouring the MF group on the social functioning scale at treatment cycle 6 and on the Global QoL scale at treatment cycles 5 and 6. On most symptom and single-item scales there were no statistically significant differences between the groups. However, at baseline, the T patients reported more appetite loss, at treatment cycles 2-4, the MF patients reported more nausea/vomiting, and at treatment cycle 6, the T patients reported more symptoms of fatigue, dyspnoea and insomnia. There were no statistically significant differences between the groups in the mean change scores of the functional and symptom scales. Interindividual variance was, however, larger in the T group. Differences in QoL between the two treatment groups were minor. Hence, given the expectancy of comparable QoL outcomes, the choice of treatment should be made on the basis of the expected clinical effect.

Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group.

The aim of this study was to compare the efficacy and tolerability of docetaxel to methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure. A randomised multicentre trial was conducted in 283 patients with advanced breast cancer who had failed previous anthracycline treatment. Docetaxel at a dose of 100 mg/m2 every 3 weeks (n = 143) was compared with sequential methotrexate and 5-fluorouracil (MF; n = 139) given at day 1 and 8 every 3 weeks at dosages of 200 mg/ m2 and 600 mg/m2, respectively. After progression, crossover to the alternative treatment group was recommended. There was a significantly higher overall response rate in the docetaxel 42% (CR 8% + PR 34%) than in the MF arm 21% (CR 3% + PR 18%) (P < 0.001). The median time to progression (TTP) was 6.3 months in the docetaxel arm and 3.0 months in the MF arm (P < 0.001). Docetaxel also had a significantly higher response rate of 27% following crossover compared with MF (12%). Significantly more side-effects (leucopenia, infections, neuropathy, oedema, asthenia, skin, nail changes, alopecia) were seen in the docetaxel than in the MF group. However, grade 3 and 4 side-effects were infrequent with both drugs, with the exception of fatigue, alopecia and infections. Median overall survival (OS) including crossover phase was 10.4 months in the docetaxel and 11.1 months in the MF arm (P = 0.79). Based on the response rate and the primary endpoint of TTP, docetaxel is superior to sequential methotrexate and 5-fluorouracil in advanced breast cancer after anthracycline failure.