Prostate and breast cancer in four Nordic countries: A comparison of incidence and mortality trends across countries and age groups 1975-2013.

In recent decades, management of prostate and breast cancer patients has changed considerably. The purpose of our study is to interpret patterns of prostate and breast cancer incidence and mortality in four Nordic countries across age groups and time periods. Prostate and breast cancer incidence and mortality data (1975-2013) were obtained from the NORDCAN database. Joinpoint regression models were used to identify changes in the trends. A more prominent increase in prostate than breast cancer incidence was observed. From the mid-1990s, mortality rates in patients below 75 years of age have decreased for both cancers in all four countries. The relative decline in breast cancer mortality from 1985-1989 to 2009-2013 were largest in women under 50 years of age, with reductions in mortality rates ranging from 38% in Finland to 55% in Denmark. In the age group 55-74 years, mortality rates for prostate cancer declined more than for breast cancer in all countries except Denmark, ranging from 14% in Denmark to 39% in Norway. The substantial decrease in breast cancer mortality in women below regular screening age and the reductions in mortality from both cancers in Denmark from the mid-1990s are consistent with beneficial contributions from improved treatment besides mammography screening and increased PSA testing. Alongside similar mortality decreases, the larger increases in prostate cancer incidence as compared to breast cancer indicate that a higher proportion of prostate cancer cases are overdiagnosed.

Pre-diagnostic high-sensitive C-reactive protein and breast cancer risk, recurrence, and survival.

Inflammation may initiate and promote breast cancer development, and be associated with elevated circulating levels of inflammation markers. A total of eight 130 initially healthy women, participated in the population-based Tromsø study (1994-2008). Pre-diagnostic high-sensitivity C-reactive protein (hs-CRP) was assessed. During 14.6 years of follow-up, a total of 192 women developed invasive breast cancer. These cases were followed for additional 7.2 years. Detailed medical records were obtained. We observed an overall positive dose-response relationship between pre-diagnostic hs-CRP and breast cancer risk (hazard ratio (HR) = 1.06, 95 % CI 1.01-1.11). Postmenopausal women with above median levels of hs-CRP (>1.2 mg/l) had a 1.42 (95 % CI 1.01-2.00) higher breast cancer risk compared to postmenopausal women with hs-CRP below median. Postmenopausal women, who were hormone replacement therapy non-users, and were in the middle tertile (0.8-1.9 mg/l), or highest tertile of hs-CRP (>1.9 mg/l), had a 2.31 (95 % CI 1.31-4.03) and 2.08 (95 % CI 1.16-3.76) higher breast cancer risk, respectively, compared with women in the lowest tertile. For each unit increase in pre-diagnostic hs-CRP levels (mg/l), we observed an 18 % increase in disease-free interval (95 % CI 0.70-0.97), and a 22 % reduction in overall mortality (95 % CI 0.62-0.98). Our study supports a positive association between pre-diagnostic hs-CRP and breast cancer risk. In contrast, increased pre-diagnostic hs-CRP was associated with improved overall mortality, but our findings are based on a small sample size, and should be interpreted with caution.

Polymorphisms in the estrogen receptor alpha gene (ESR1), daily cycling estrogen and mammographic density phenotypes.

BACKGROUND: Single nucleotide polymorphisms (SNPs) involved in the estrogen pathway and SNPs in the estrogen receptor alpha gene (ESR1 6q25) have been linked to breast cancer development, and mammographic density is an established breast cancer risk factor. Whether there is an association between daily estradiol levels, SNPs in ESR1 and premenopausal mammographic density phenotypes is unknown. METHODS: We assessed estradiol in daily saliva samples throughout an entire menstrual cycle in 202 healthy premenopausal women in the Norwegian Energy Balance and Breast Cancer Aspects I study. DNA was genotyped using the Illumina Golden Gate platform. Mammograms were taken between days 7 and 12 of the menstrual cycle, and digitized mammographic density was assessed using a computer-assisted method (Madena). Multivariable regression models were used to study the association between SNPs in ESR1, premenopausal mammographic density phenotypes and daily cycling estradiol. RESULTS: We observed inverse linear associations between the minor alleles of eight measured SNPs (rs3020364, rs2474148, rs12154178, rs2347867, rs6927072, rs2982712, rs3020407, rs9322335) and percent mammographic density (p-values: 0.002-0.026), these associations were strongest in lean women (BMI, ≤23.6 kg/m2.). The odds of above-median percent mammographic density (>28.5 %) among women with major homozygous genotypes were 3-6 times higher than those of women with minor homozygous genotypes in seven SNPs. Women with rs3020364 major homozygous genotype had an OR of 6.46 for above-median percent mammographic density (OR: 6.46; 95 % Confidence Interval 1.61, 25.94) when compared to women with the minor homozygous genotype. These associations were not observed in relation to absolute mammographic density. No associations between SNPs and daily cycling estradiol were observed. However, we suggest, based on results of borderline significance (p values: 0.025-0.079) that the level of 17ß-estradiol for women with the minor genotype for rs3020364, rs24744148 and rs2982712 were lower throughout the cycle in women with low (<28.5 %) percent mammographic density and higher in women with high (>28.5 %) percent mammographic density, when compared to women with the major genotype. CONCLUSION: Our results support an association between eight selected SNPs in the ESR1 gene and percent mammographic density. The results need to be confirmed in larger studies.

Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer.

BACKGROUND: The objective of this study was to assess markers of spermatogenesis in long-term survivors of testicular cancer (TC) according to treatment, and to explore correlations between the markers and associations with achieved paternity following TC treatment. METHODS: In 1191 TC survivors diagnosed between 1980 and 1994, serum-follicle stimulating hormone (s-FSH; n=1191), s-inhibin B (n=441), and sperm counts (millions per ml; n=342) were analysed in a national follow-up study in 1998-2002. Paternity was assessed by a questionnaire. RESULTS: At median 11 years follow-up, 44% had oligo- (<15 millions per ml; 29%) or azoospermia (15%). Sperm counts and s-inhibin B were significantly lower and s-FSH was higher after chemotherapy, but not after radiotherapy (RT), when compared with surgery only. All measures were significantly more abnormal following high doses of chemotherapy (cisplatin (Cis)>850 mg, absolute cumulative dose) compared with lower doses (Cis ≤ 850 mg). Sperm counts were moderately correlated with s-FSH (-0.500), s-inhibin B (0.455), and s-inhibin B : FSH ratio (-0.524; all P<0.001). All markers differed significantly between those who had achieved post-treatment fatherhood and those with unsuccessful attempts. CONCLUSION: The RT had no long-term effects on the assessed markers of spermatogenesis, whereas chemotherapy had. At present, the routine evaluation of s-inhibin B adds little in the initial fertility evaluation of TC survivors.

Interaction between perceived self-motion and object-motion impairs vehicle guidance.

When one is riding in a vehicle, perceptual thresholds for motion of objects are significantly elevated above those determined under corresponding but simulated conditions in the laboratory without concurrent self-motion perception. Authorities on road traffic accidents should thus consider an additional perceptual time of at least 300 milliseconds for detecting critical changes in headway beyond the usual reaction time. Detection times thus corrected consequently lead to an alteration of our conception of safe intervehicle distances in a convoy. This elevation of thresholds for object-motion during self-motion, with its consequences for visual control of vehicle guidance, can be seen as a disadvantageous side effect of an otherwise beneficial space-constancy mechanism, which provides us with a stable world during locomotion.

TENS and optokinetic stimulation in neglect therapy after cerebrovascular accident: a randomized controlled study.

BACKGROUND: In a randomized controlled type Ib study, the effectiveness of three different forms of therapy for the treatment of visual neglect was assessed by comparing therapy outcomes in three groups of patients after cerebrovascular accidents. METHODS: A control group received only standard exploration training, whilst the second and third group received exploration training combined with either contralateral transcutaneous electrical nerve stimulation (TENS) or optokinetic stimulation (OKS) respectively. RESULTS: It was found that exploration training alone resulted in no improvement on both standard neglect tests (NTs) and everyday-relevant measures of reading and writing performance. In contrast, the groups receiving TENS or OKS showed significant improvements in both sets of measures with the difference that for the TENS group the improvement in NT scores at the end of therapy had disappeared 1-week later. However, both treatments resulted in significant improvements in reading and writing which were still present upon retesting 1-week after the end of therapy. CONCLUSION: Both methods can be recommended for neglect therapy and are superior to exploration therapy alone.

Blood pressure and body mass index in long-term survivors of testicular cancer.

PURPOSE: To evaluate blood pressure and body mass index (BMI) in long-term survivors of testicular cancer (TC) treated with different modalities. PATIENTS AND METHODS: One thousand eight hundred fourteen patients treated for unilateral TC in Norway (1980 to 1994) were invited to participate in a follow-up study (1998 to 2002), including measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP), and BMI. Of these patients, 1,289 patients (71%) participated in the study. The patients were categorized into four treatment groups: surgery (n = 242), radiotherapy (n = 547), and two chemotherapy groups, cumulative cisplatin dose < or = 850 mg (n = 402) and cumulative cisplatin dose more than 850 mg (n = 98). A control group consisted of healthy males from the Tromsø Population Study (n = 2,847). RESULTS: At diagnosis, age-adjusted regression analyses showed no differences between the treatment groups for any variables. After a median follow-up time of 11.2 years, age-adjusted SBP and DBP were significantly higher for both chemotherapy groups compared with the surgery group. Chemotherapy-treated patients had increased odds for hypertension at follow-up compared with the surgery group, and the odds were highest for the cisplatin more than 850 mg group (odds ratio = 2.4; 95% CI, 1.4 to 4.0). The cisplatin more than 850 mg group had a significantly higher 10-year BMI increase and a higher prevalence of obesity at follow-up than the surgery group. Compared with healthy controls, chemotherapy-treated patients had, at follow-up, increased SBP, increased DBP, excessive BMI increase, and a higher prevalence of hypertension. CONCLUSION: Five to 20 years after therapy, cured TC patients treated with cisplatin-based chemotherapy had significantly higher levels of blood pressure, a higher prevalence of hypertension, and an excessive weight gain compared with patients treated with other modalities and compared with healthy controls.

Dose-dependent pharmacokinetics of methotrexate and 7-hydroxymethotrexate in the rat in vivo.

The pharmacokinetics of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) in bile, urine, and serum was studied in rats in vivo after short-time infusions of 10, 50, 250, and 1000 mg/kg MTX. All animals were anesthetized and drained of bile during experiments. The biliary secretion rate of MTX approached saturation when serum MTX levels surpassed 700-800 microM, causing a significant reduction in biliary recovery as the parent compound (49 to 32%) at MTX doses exceeding 50 mg/kg. The hepatic metabolism of MTX to the 7-hydroxy metabolite was not saturated at the doses used. Serum MTX pharmacokinetics demonstrated dose dependency, inasmuch as doses exceeding 10 mg/kg were accompanied by a reduced total body clearance (Clr) and biliary clearance (ClB). A significant finding in relation to acute hepatotoxicity reported after high-dose MTX in humans was the occurrence of cholestasis 30-90 min after drug infusion and the observation of macroscopic precipitations in the bile duct in five of six animals treated with 1000 mg/kg MTX. In these five animals, cessation of bile secretion occurred at similar bile 7-OH-MTX levels [9800 +/- 1100 (SD) microM], while the single rat that secreted bile throughout the experiment had a 5-fold lower peak 7-OH-MTX concentration in bile. Analysis of biliary precipitates formed in vivo and in vitro found 7-OH-MTX to constitute 97% and MTX 3% of the drug content of the precipitated material.

Formation and elimination of 7-hydroxymethotrexate in the rat in vivo after methotrexate administration.

Bile, urine, and serum concentrations of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) were monitored in rats in vivo following a short-time infusion of 10 mg/kg [3H]MTX. The experiments were performed in one group of anesthetized, bile-drained rats and in two control groups, one anesthetized and one unanesthetized, that were not bile-drained. Peak biliary levels of MTX (3.8 x 10(-3) M) and 7-OH-MTX (1.8 x 10(-4) M) appeared within 15 min after cessation of infusions. For two log ranges of serum MTX concentrations, biliary levels remained 180-fold higher. High bile 7-OH-MTX levels appeared few min after start of MTX administration, and were 720 times higher than the peak serum concentrations, indicating that the liver is a major site of 7-OH-MTX formation in the rat. 7-OH-MTX concentrations in bile declined monophasically with a half-life of 29.4 min, while MTX showed a biphasic elimination with initial and second phase half-lives of 23.1 and 86.4 min, respectively. Bile was the major excretory route for MTX and 7-OH-MTX, with 50% of the dose recovered as the parent compound and 3.6% as the metabolite. There was no difference in urinary recovery of MTX in bile-drained and control animals, indicative of insignificant enterohepatic circulation of MTX. This was further corroborated by the finding of just 2.1% urinary recovery of MTX in rats who received previously collected MTX-containing bile through a duodenal catheter. Serum concentration curves were analyzed according to a three-compartment open model with an initial elimination half-life of 1.7-3.3 min, a second phase half-life of 15.4-21.0 min, and a terminal phase half-life of 119-240 min. Our finding of 7-OH-MTX formation and high biliary levels of the metabolite in the rat, can be used as basis for studies of interactions with in vivo MTX conversion to the 7-hydroxy metabolite.

Partial purification of deoxyuridine triphosphate nucleotidohydrolase and its effect on DNA synthesis in isolated HeLa cell nuclei.

Deoxyuridine triphosphate nucleotidohydrolase (EC 3.6.U.23) has been partially purified from HeLa S3 cells, and found to have an apparent molecular weight of 50--55 000 by gel filtration under non-denaturing conditions. The enzyme is specific for the hydrolysis of dUTP, requires Mg2+ and is inhibited by EDTA. The apparent Km for dUTP is 0.1 microM. Isolated HeLa cell nuclei were treated with dUTPase before pulse-labelling with [3H]dTTP which also had been pretreated with dUTPase. This pretreatment changed neither the total amount nor the size of the primary DNA pieces. A role for dUTP incorporation in their genesis can therefore be excluded and these primary DNA pieces are considered to be true intermediates in discontinuous DNA replication.

The role of DNA polymerases alpha, beta and gamma in nuclear DNA synthesis.

The effects of the inhibitors 2'3' dideoxythymidine triphosphate (ddTTP) and 1-beta-D-arabinofuranosyl cytosine triphosphate (araCTP) on DNA synthesis in isolated S-phase HeLa S3 nuclei have been examined. These effects are compared with the effects of the same inhibitors in partially purified preparations of DNA polymerases alpha and beta. The effect of ddTTP on partially purified DNA polymerase gamma was also tested. DNA polymerases beta and gamma were very sensitive to ddTTP whereas DNA polymerase alpha and DNA synthesis in isolated nuclei were quite resistant. The synthesis and subsequent ligation of primary DNA pieces ('Okazaki fragments') were not affected by the presence of this inhibitor. DNA synthesis in isolated nuclei and DNA polymerase alpha activity were very sensitive to araCTP whereas DNA polymerase beta was almost totally resistant to the inhibitor. The results indicate a major role for DNA polymerase alpha in DNA replication.

Accumulation of small fragments of DNA in isolated HeLa cell nuclei due to transient incorporation of dUMP.

[3H]dUMP was incorporated into DNA of isolated S-phase HeLa S3 cell nuclei during DNA synthesis. The incorporated radioactivity was made acid soluble during a chase with excess TTP. A partially purified DNA polymerase alpha incorporated [3H]dUMP into activated salmon sperm DNA. The incorporation rate was equal to the incorporation of [3H]TMP, and the radioactivity incorporated was not made acid soluble during a chase. The nuclei thus have the ability to remove misincorporated uracil. From cytosol we have partially purified an enzyme (80 times purification) that splits the N-glycosidic bond between uracil and deoxyribose in dUMP-containing DNA. This uracil-N-glycosidase has a molecular weight of about 50 000. It does not accept dUTP or RNA as substrates. Pulse labelling of isolated nuclei with radioactive deoxyribonucleoside triphosphates in the presence of dUTP lead to a large accumulation of label in small DNA fragments. The size of these fragments was about 80 nucleotides in a 60 s pulse and no increase in size was observed with increasing pulse length. The corresponding value for control experiments with no dUTP, was 200 nucleotides and the fragments increased in size with increasing pulse length. About 90% of the radioactivity was found in the small fragments after a 3 min pulse when the concentration of dUTP in the test mixture was 100 micrometer and no exogenous TTP was present. In control experiments with no dUTP present, only 14% of the radioactivity was found in small DNA pieces. When test mixture containing dUTP was preincubated with cytosol for 60 s before adding the isolated nuclei, the small fragments increased in size to that of DNA fragments found in control incubations; also the relative amount of label bound to the fragments returned to the levels found in the controls. Increasing the TTP concentration from 5 micrometer to 1.88 mM in the absence of exogenous dUTP had no effect on the size of the DNA fragments.

DNA replication intermediates in whole HeLa cells and isolated nuclei.

Replicative intermediates have been studied in intact HeLa cells and in nuclei isolated from such cells. In whole cells the smallest DNA (primary DNA pieces) observed after pulse labelling with [3H]thymidine were 90-160 nucleotides long, and the size of the molecules in this class of DNA did not increase with increasing pulse length. Some increase in size was, however, observed when cells were pulse labelled at 25 degrees C instead of 37 degrees C. Chase experiments using nuclei from pulse-labelled cells suggested that the primary DNA pieces could be chased rapidly into DNA of high molecular weight (30-70 S, corresponding to a molecular weight of 0.7 - 10(7)-6.4-10(7)). Longer chases showed that the label eventually accumulated in DNA with s values greater than 150 S. In isolated nuclei the primary DNA pieces after a 1 min pulse at 37 degrees C were approximately 200 nucleotides long. Primary pieces of this size were also rapidly chased into the 30-70 S region. However, during longer pulses in vitro a fraction of the primary DNA pieces grew beyond their normal size to reach a size of up to 2000-3000 nucleotides before being attached to the 30-70 S molecules.

Cancer patients use of nonproven therapy: a 5-year follow-up study.

PURPOSE: To investigate the prospective pattern of use of alternative medicine, here called nonproven therapy (NPT), among oncologic patients during a 5-year period, and the relationship between this use and survival, a questionnaire-based follow-up study was performed at the Department of Oncology, University of Tromsø, from 1990 to 1996. PATIENTS AND METHODS: Two-hundred fifty-two patients answered the first questionnaire during the period July 1990 to July 1991. Eligible patients were mailed follow-up questionnaires after 4, 12, 24 and 60 months. A telephone interview performed after the last follow-up questionnaire showed little disagreement with the prospective collected information as regards the number of patients reported as users of NPT (kappa, 0.92). RESULTS: The number of patients who reported ever using NPT in each cross-sectional part of the study varied between 17.4% and 27.3%. However, the estimated cumulative risk of being a user of NPT during the follow-up period was 45%. Seventy-four percent of NPT users in this north Norwegian study population used faith healing or healing by hand (spiritual NPT) alone or in combination with other forms of NPT. The proportion of patients who used spiritual versus nonspiritual forms of NPT was consistent throughout the follow-up period. Women were more often users than men (50% v 31%, P = .002). Patients older than 75 years of age seldomly used NPT. The 5-year observed survival rate was not influenced by the use of NPT. Adjusted for sex, age, and diagnosis, patients with a high educational level had a borderline higher 5-year survival rate than patients with less education (P = .06). CONCLUSION: Our results demonstrate that cross-sectionally designed studies will underestimate the number of ever-users of NPT in a cancer patient population. The use of NPT does not influence observed survival among cancer patients seen in north Norway.

Predictive value of p53, mdm-2, p21, and mib-1 for chemotherapy response in advanced breast cancer.

p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. The protein product of the murine double minute gene 2 (mdm-2) plays a central role in the regulation of p53. In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. In breast cancer patients, it is unclear whether measuring p53, mdm-2, or p21 expression provides information on how patients will respond to chemotherapy. Mib-1 monoclonal antibody recognizes the proliferation-related antigen Ki-67. High tumor proliferation has previously been associated with response to chemotherapy. p53, mdm-2, p21, and mib-1 expression were assessed by immunohistochemical methods in primary tumors derived from 134 patients who took part in a randomized multicenter trial comparing docetaxel to sequential methotrexate and 5-fluorouracil (MF) in advanced breast cancer. Low mib-1 staining correlated with negative p53 staining (P = 0.001), and mdm-2 and p21 stainings correlated positively with each other (P < 0.001). p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. However, in the MF group, a low mib expression (<25%) and a high mdm-2 expression (> or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. p53 staining status was not associated with response to treatment in either group. Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response.

Treatment intention in hospitalized cancer patients in oncological wards in Norway: a national survey.

Clinicians often do not agree whether a treatment is given with a palliative or curative intent. A common clear definition does not exist. This study has assessed the usefulness of dividing the goal of treatment into three distinct categories: curative treatment; palliative, symptom preventive treatment; and palliative, symptom relieving treatment. In a cross-sectional study among all cancer centres in Norway, a total of 629 patients were included into the study. Of these patients, 60% received palliative treatment, with an equal distribution between symptom preventive and symptom relieving. The definitions were found easy to use by the physicians. It gave important information of differences between cancer diagnosis with respect to the number of patients receiving palliative treatment. In order to refine the classification system, the authors will, in future studies, include a fourth category, life prolonging treatment, which is located between curative and palliative treatment with respect to treatment intensity.

Interethnic difference in thiopurine methyltransferase activity.

A number of metabolic pathways are subject to both genetic polymorphism and interethnic differences. A catabolic pathway of 6-mercaptopurine, red blood cell (RBC) thiopurine methyltransferase (TPMT) activity showed genetic polymorphism in Caucasians, but variation according to ethnicity has not been studied. We investigated if red blood cell thiopurine methyltransferase was subject to interethnic variation in a Saami (Lappish; n = 36) and a Caucasian population (n = 50). The Saami population sample had 29% higher thiopurine methyltransferase activity, 17.0 +/- 3.3 U/ml red blood cell compared with the Caucasian population sample, 13.1 +/- 2.9 U/ml red blood cell (p much less than 0.001). Probit plots and frequency distribution histograms supported bimodality consistent with genetic polymorphism in both study populations. Differences in chronic diseases, drug consumption, age, or gender could not explain the interethnic difference in red blood cell thiopurine methyltransferase activity. The higher red blood cell thiopurine methyltransferase activity in the Saami population group indicates that these subjects may require higher dosages of thiopurine drugs than Caucasians.

Testicular cancer treated in a minor general oncology department.

The question of where to treat testicular cancer and by whom has been debated in several medical journals over the last few year. Here we present data from 98 patients (47 seminomas, 51 non-seminomas) treated between January 1985 and March 1993 at the Department of Oncology, University Hospital of Tromsø, Norway. During a 4-year median follow-up period 2 patients died of progressive disease. Our results are similar to those of major specialised oncology centres. We argue that within the context of multicentre cooperative studies or treatment protocols, patients with testicular cancer can be treated in a small general oncology centre with the same expectations of cure and treatment-related mortality and morbidity as achieved in major centres.

Cancer patients, doctors and nurses vary in their willingness to undertake cancer chemotherapy.

Cancer patients' attitude to chemotherapy were compared with those of doctors, nurses and healthy controls. 98 cancer patients, 42 healthy subjects, 44 oncologists, 35 surgeons, 32 oncology nurses and 70 surgical nurses received a questionnaire presenting a hypothetical situation involving a toxic chemotherapy regimen. Each were asked to indicate the minimal benefit with respect to chance of cure, life prolongation and symptom relief they would demand to accept the treatment. The patients and the surgical nurses were most reluctant with regard to the treatment. The subgroup of patients under 50 years which matched the oncologists, surgeons and controls with respect to age, cohabitant status and children were significantly more willing to accept the regimen than the controls and professional groups. Patients under 40 years would accept the toxic treatment with hardly any benefit as chance of cure (7%, median), life prolongation (3 months) and symptom relief (8%). Among the professionals, oncologists were most willing to accept therapy, whereas surgical nurses and surgeons were least willing.

Weekly doxorubicin with or without high-dose medroxyprogesterone acetate in hormone-resistant advanced breast cancer. A randomised study. The Norwegian Breast Cancer Group.

In a randomised study, 218 patients with advanced breast cancer, resistant to hormone therapy, received either doxorubicin 20 mg every week (Awkly) alone or Awkly combined with high doses (1000 mg daily) of oral medroxyprogesterone acetate (HD-MPA). Of the 210 evaluable patients, the response rates were 26% [95% confidence interval (CI) 18-34%] for Awkly and 38% (95% CI 29-47%) for Awkly + HD-MPA (P = 0.08). There was no significant difference with regard to duration of response. Median survival was 11 months in both groups. Considerable toxicity was seen from HD-MPA, particularly weight gain and fluid retention. The present study provides evidence that, in concordance with preclinical studies and a previous randomised study, interaction between chemotherapy and HD-MPA may exist in breast cancer normally resistant to hormone therapy. For further studies, other gestagens and/or a dose reduction could be investigated.