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.

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.

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.

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.

Weekly Paclitaxel plus Capecitabine versus Docetaxel Every 3 Weeks plus Capecitabine in Metastatic Breast Cancer.

Background. We performed a randomized phase II study comparing efficacy and toxicity of weekly paclitaxel 80 mg/m(2) (Weetax) with three weekly docetaxel 75 mg/m(2) (Threetax), both in combination with oral capecitabine 1000 mg/m(2) twice daily for 2 weeks followed by a 1-week break. Patients. Thirty-seven women with confirmed metastatic breast cancer were randomized. Results. Median TTF was 174 (Weetax) versus 147 days (Threetax) (P=0.472). Median OS was 933 (Weetax) versus 464 days (Threetax) (P=0.191). Reasons for TTF were PD 8/18 (Weetax), 9/19 (Threetax); and toxicity: 8/18 (Weetax), 8/19 (Threetax). ORR was 72% (Weetax) versus 26% (Threetax) (P = 0.01). The Threetax-combination resulted in a higher incidence of leuco-/neutropenia compared to Weetax. Grade II anemia was more pronounced in the Weetax group. No difference was found in quality of life. Conclusion. Taxanes in combination with capecitabine resulted in a high level of toxicity. Taxanes and capecitabine should be considered given sequentially and not in combination.

Predicted cardiovascular mortality and reported cardiovascular morbidity in testicular cancer survivors.

INTRODUCTION: We examined if testicular cancer (TC) treatment is associated with any risk for cardiovascular morbidity or predicted mortality according to the SCORE model, in which a 10-year future risk of >or=5% for developing a fatal cardiovascular event qualify for high-risk status. METHODS: One thousand one hundred thirty-four TC survivors treated 1980-1994 participated in this study (1998-2002). Patients were categorised in four treatment groups: surgery (n = 225), radiotherapy (n = 445), and two chemotherapy groups: cumulative cisplatin dose 850 mg (cis>850, n = 89). Patients with cardiovascular disease, diabetes or SCORE >or=5% constituted a high-risk group, and those with SCORE >1% an intermediate/high risk group. RESULTS: Age-adjusted mean SCORE was 0.93% for the surgery group. In comparison, chemotherapy treated patients had significantly higher SCORE (1.07%, p = 0.01). Only 15% of patients were scored to be at high-risk, while 53% qualified for the intermediate/high risk group. Patients in the cis>850 group had increased odds for having intermediate/high risk, compared with the surgery group (OR 3.4, 95% CI 1.3-8.7). Only 23 cardiovascular events had occurred since the testicular cancer diagnosis. CONCLUSION: The SCORE model indicates that patients treated with cisplatin-based chemotherapy have a significantly increased future risk of a fatal cardiovascular event. IMPLICATIONS FOR CANCER SURVIVORS: TC survivors should be followed regularly with respect to cardiovascular risk profile beyond the routine 10-year clinical follow-up.

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.

Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis.

Trastuzumab has shown activity in early breast cancer patients that overexpress HER2. Significant resources have to be allocated to finance this therapy, underlining the need for cost-effectiveness analysis. A model was set up, societal costs were calculated and the discount rate was 3%. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% absolute improvement in overall survival (OS)). The comparator was the FEC(100) regimen. The median additional health care cost per patient treated was 33,597 euros. The yielding cost per life year gained (LYG) was 15,341 euros with a 20% improved OS and 35,947 euros with 10% improved OS. The corresponding net health care cost per quality adjusted life year (QALY) was 19,176 euros and 44,934 euros. Including all resource use the figures were 8148 euros and 30,290 euros per LYG. Sensitivity analyses documented survival gain, price of trastuzumab, production gain and discount rate to be the major factors influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in Norway.

Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy.

BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.

Components of the metabolic syndrome in long-term survivors of testicular cancer.

BACKGROUND: A possible explanation of the excess cardiovascular risk in testicular cancer (TC) survivors is development of metabolic syndrome. The association between metabolic syndrome and TC treatment is examined in long-term survivors. PATIENTS AND METHODS: In a national follow-up study (1998-2002), 1463 TC survivors (diagnosed 1980-1994) participated. Patients >60 years were excluded in the present study, leaving 1135 patients eligible. The patients were divided in four treatment groups: surgery (n = 225); radiotherapy (n = 446) and two chemotherapy groups: cumulative cisplatin dose (Cis) 850 mg (n = 88). A control group consisted of 1150 men from the Tromsø Population Study. Metabolic syndrome was defined according to a modified National Cholesterol Education Program definition. RESULTS: Both chemotherapy groups had increased odds for metabolic syndrome compared with the surgery group, highest for the Cis >850 group [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.6-4.7]. Also, the Cis >850 group had increased odds (OR 2.1, 95% CI 1.3-3.4) for metabolic syndrome compared with the control group. The association between metabolic syndrome and the Cis >850 group was strengthened after adjusting for testosterone, smoking, physical activity, education and family status. CONCLUSION: TC survivors treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome compared with patients treated with other modalities or with controls.

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.

Use of complementary and alternative therapies: a national multicentre study of oncology health professionals in Norway.

GOALS OF WORK: It is well documented that an increasing proportion of cancer patients today use complementary and alternative medicine, mostly alongside conventional therapies. This study investigates the use of complementary and alternative medicine among oncology health workers and the reported effects. PATIENTS AND METHODS: In June 2002, we conducted a national multicentre survey including 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. The response rate was 61.5%. MAIN RESULTS: We found that females were more often users of both complementary and alternative methods than males (39% versus 15% and 47% versus 17%) and that few oncologists had tried such treatments compared to nurses, therapeutic radiographers and clerks (20/12% versus 50/40%, 41/33%,and 31/50%). Interestingly, the majority of those who had tried unconventional methods reported some or very good effects. Acupuncture, homeopathy, aromatherapy and massage were the most popular therapies. Sub-group analyses including only oncologists showed that female physicians were more often users of both complementary and alternative methods compared to males (33% versus 12%, 25% versus 3%). Moreover, participants below the age of 35 years and Christians more often reported use. CONCLUSIONS: This survey demonstrates that significant proportion of oncology health workers in Norway have used non-proven therapies and that most have had a positive experience. Differences in use is highly dependent on gender, profession, age and religion.

Knowledge of and attitudes toward complementary and alternative therapies; a national multicentre study of oncology professionals in Norway.

This study reports on oncology professionals' knowledge and attitude toward complementary and alternative medicines (CAM), classified according to their primary application as complementary or alternative methods. In June 2002, we conducted a national, multicentre survey of 828 Norwegian oncologists, nurses, clerks and therapeutic radiographers. A response rate of 61% was achieved. Only a few physicians (4%) described their reactions to alternative medicine as positive compared with nurses (33%), therapeutic radiographers (32%) and clerks (55%) (P<0.0001). Females showed a more positive view than males (33% versus 14%, P<0.0001). More participants expressed a positive attitude to complementary versus alternative medicines. Most respondents regarded healing by hand or prayer, homeopathy, and Iscador (mistletoe) as alternative therapies. In contrast, most respondents classified acupuncture, meditation, reflexology, music/art-therapy, aromatherapy and massage as complementary therapies. This survey demonstrates major differences, by gender as well as oncology health profession in views about and the classification of various CAM methods.

The level of physical activity in long-term survivors of testicular cancer.

The aim of this study was to estimate the level of physical activity (LPA) in a large cohort of testicular cancer survivors (TCSs) and compare these results with observations from men in the same age range in the general population (GenPop). We also wanted to identify parameters that influenced physical activity. The study populations consisted of 1276 TCSs treated with surgery, radiotherapy or chemotherapy with or without surgery (mean observation time was 12 years), and 20391 male inhabitants from a Norwegian county (GenPop). All completed a question investigating two sub-levels of physical activity. The logistic regression analysis adjusting for different covariates, showed significantly more physically active men among the TCSs compared with the GenPop (43 versus 37%) (adjusted odds ratio (aOR)=1.32 (95% Confidence Interval (CI) 1.10-1.58)). The results indicate that the experience of testicular cancer increases rather than reduces the LPA in TCSs, independent of treatment given.

Does use of alternative medicine predict survival from cancer?

This study examines the association between alternative medicines (AM) and cancer survival. A national multicentre study was carried out in Norway in December 1992 to assess the prevalence of AM use among cancer patients. One of the aims of this study was to assess the association between AM and long-time survival. In January 2001, survival data were obtained with a follow-up of 8 years for 515 cancer patients. A total of 112 (22%) assessable patients used AM. During the follow-up period, 350 patients died. Death rates were higher in AM users (79%) than in those who did not use AM (65%). In a Cox regression model adjusted for demographic, disease and treatment factors, the hazard ratio of death for any use of AM compared with no use was 1.30, (95% Confidence Interval (CI) 0.99, 1.70; P=0.056), suggesting that AM use may predict a shorter survival. Sensitivity analyses strengthened the negative association between AM use and survival. AM use had the most detrimental effect in patients with an ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 (hazard ratio for use=2.32, 95% CI, 1.44, 3.74, P=0.001), when compared with an ECOG PS of 1 or higher. The use of AM seems to predict a shorter survival from cancer. The effect appears predominantly in patients with a good PS.

Tumour microvessel density as predictor of chemotherapy response in breast cancer patients.

The aim of this study was to evaluate the predictive value of intratumoural microvessel density in breast cancer. We studied immunohistochemically primary tumours of 104 patients with metastasised breast cancer who took part in a randomised multicentre trial comparing docetaxel to sequential methotrexate and 5-fluorouracil. Vessels were highlighted with factor VIII staining and counted microscopically. Microvessel density was compared with clinical response to chemotherapy and patient survival. The microvessel density of the primary tumour was not significantly associated with patient's response to chemotherapy, time to progression or overall survival in the whole patient population or in the docetaxel or methotrexate and 5-fluorouracil groups. However, disease-free survival was longer in patients with low microvessel density (P=0.01). These findings suggest that microvessel density of the primary tumour cannot be used as a predictive marker for chemotherapy response in advanced breast cancer.

C-erbB-2 expression does not predict response to docetaxel or sequential methotrexate and 5-fluorouracil in advanced breast cancer.

Breast cancer patients with c-erbB-2-positive tumours seem to benefit from anthracycline-based adjuvant chemotherapy. The predictive value of c-erbB-2 for taxane sensitivity is not yet clear. The purpose of this study was to assess whether c-erbB-2 expression is associated with clinical sensitivity to docetaxel (T) or sequential methotrexate and 5-fluorouracil (MF). A total of 283 patients with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel with sequential MF in advanced breast cancer. Paraffin-embedded blocks of the primary tumour were available for 131 patients (46%). c-erbB-2 status was determined by immunohistochemistry using a polyclonal antibody to the c-erbB-2 protein. C-erbB-2 expression was scored in a semi-quantitative fashion using a 0 to 3+ scale. Staining scores 2+ or greater were considered positive. Response evaluation was performed according to World Health Organization (WHO) recommendations. Overall 54 (42%) patients had c-erbB-2-positive tumours. There was no association between treatment outcome and c-erbB-2 overexpression. The overall response rates (RR) (n=128) among c-erbB-2-negative and -positive patients were 35 and 44%, respectively (P=0.359). In the MF arm (n=62), the RR was somewhat higher in the c-erbB-2 overexpressors (33% versus 18%, P=0.18). In the docetaxel arm the RRs were very similar, regardless of the c-erbB-2 expression (53% versus 53%). While several studies have suggested a prognostic and putative predictive significance of c-erbB-2 overexpression in early breast cancer, the significance of c-erbB-2 expression as a predictive factor for response to various cytotoxic treatments in advanced breast cancer is still controversial. In this study, c-erbB-2 expression could not predict response to either MF or T. Thus, tumours over-expressing c-erbB-2 are not uniformly more sensitive to taxanes and c-erbB-2 expression cannot yet be applied clinically as a predictive factor for response in advanced breast cancer.

[Terminal care of cancer patients]. / Terminalomsorg til kreftpasienter.

BACKGROUND: Palliative medicine is increasingly important in the health services. MATERIAL AND METHODS: The records of 52 patients who died in the department of oncology of Ullevaal University Hospital, July to December 1999 were examined. Major symptoms at the time of admission, information, communication, and the quality of the patient records were registered. RESULTS: 50 out of 52 patients had severe pain at admission. Only five patients were in contact with the community care system at the time of admission. There was insufficient documentation in the patients' records of whether the patients themselves or their next of kin were sufficiently informed about their situation. INTERPRETATION: The treatment of cancer-related pain in a home-care setting could be improved. Cooperation between the hospital and home-based care is at present suboptimal. Documentation relating to terminal care in the patient records should be improved.