The Journal of Clinical Endocrinology and Metabolism, Apr 1, 1998
Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer.... more Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer. Tamoxifen is the most commonly used antiestrogen, but toremifene is gaining in popularity. We compared here the effects of tamoxifen and toremifene on bone metabolism and density in 30 postmenopausal patients with breast cancer, who were randomized to receive tamoxifen (20 mg/day, n ϭ 16) or toremifene (40 mg/day, n ϭ 14) for 1 yr. Biochemical markers of bone resorption [urinary hydroxyproline, serum cross-linked carboxyterminal telopeptide of type I collagen, urinary cross-linked aminoterminal telopeptide of type I collagen (NTx)] and bone formation [serum bone-specific alkaline phosphatase, osteocalcin, and aminoterminal and carboxyterminal propeptide of type I procollagen] were assessed before treatment and at 6 and 12 months of the antiestrogen regimen. Bone mineral density (BMD) in the lumbar spine and proximal femur (neck, trochanter, and Ward's triangle) was measured using dualenergy x-ray absorptiometry before treatment and at 12 months of treatment. Urinary NTx decreased after 6 months' use of tamoxifen (mean fall: 33%) and of toremifene (mean fall: 16%). Use of tamoxifen was associated with a significant decrease in osteocalcin (mean fall: 25%) and aminoterminal propeptide of type I procollagen (mean fall: 22%), whereas toremifene failed to influence these markers. Tamoxifen increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and 5% in Ward's triangle. Toremifene failed to increase BMD at any site measured, and in contrast, a slight trend toward a fall (Ϫ0.3 to Ϫ0.9%) in BMD was seen in patients treated with toremifene. Falls in urinary NTx, from baseline to 6 months, correlated significantly with changes in the lumbar spine BMD (r ϭ Ϫ0.57, P ϭ 0.0002) in the whole patient series. We conclude that tamoxifen (20 mg/day) increases BMD in postmenopausal breast cancer patients, whereas toremifene (40 mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged studies on bone metabolism, comparing these two antiestrogens, are needed; but even now, clinicians should be aware of these differences between tamoxifen and toremifene.
Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamin... more Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamine (10 mg/kg) or the solvent, trioctanoin. After a 2 day recovery from the surgery, the rats were placed on basal diet alone or containing phenobarbital (500 mg/kg diet), mestranol (0.2 mg/kg diet), tamoxifen (250 or 500 mg/kg diet) or toremifene (250, 500 or 750 mg/kg diet) for 6 or 18 months prior to killing. The liver and kidneys were prepared for pathological diagnoses. In addition, sections of liver from the 6 month killing were frozen and serially sectioned. The sections were stained for expression of the placental isozyme of glutathione S-transferase (GST), gamma glutamyl transpeptidase (GGT), canalicular ATPase (ATP) and glucose 6-phosphatase (G6P) and scored by quantitative stereology for number and volume fraction of liver occupied by altered hepatic foci (AHF) with alterations in these markers individually and combined (ANY). Each of the agents increased the volume fraction of liver occupied by AHF when the ANY category was used. Statistical increases in both the GGT-positive and G6P-deficient AHF populations were observed in the spontaneously as well as DEN-initiated groups treated with tamoxifen or toremifene. After 18 months of administration, the highest concentration of tamoxifen increased the incidence of malignant hepatic neoplasms in non-DEN-initiated rats. Toremifene, at the highest tested dose, increased the incidence of hepatocellular carcinomas in the DEN-initiated groups to a level one-third that observed with tamoxifen administration to DEN-initiated rats. Both tamoxifen and toremifene increased the incidence of hypernephromas in previously DEN-initiated rats. While both tamoxifen and toremifene are effective promoting agents for DEN-initiated lesions, tamoxifen is more potent than toremifene in the induction of rat hepatocarcinogenesis.
1397 consecutive suicides were committed in Finland in 1987. 60 (4.3%) of these involved cancer p... more 1397 consecutive suicides were committed in Finland in 1987. 60 (4.3%) of these involved cancer patients, 25 of whom were in remission, 18 in the terminal phase and 17 at other stages of their illness. The background of every case was explored by a structured interview of health care personnel and intimate associates and by examining medical and other case records. The factors connected with and motives for suicide were compared in the two patient groups, the terminally ill and the patients who committed suicide during remission. These groups differed markedly, with the latter having more histories of personal and family mental disorders and suicides among family members. Information which might help clinicians identify suicidal cancer patients was obtained. Withdrawal from social contacts, depression, professed suicidal thoughts and a history of suicide attempt are classical portents of suicide also in cancer patients and should not be ignored. The health care system needs to pay greater heed to the psychological needs of cancer patients. Continuity of the doctor-patient relationship should be guaranteed. Effective symptom control of the terminal patients is very important and could have been achieved in many cases through more competent treatment. Only in a very small minority of cancer patients does suicide seem rational and inevitable.
Objective: To investigate the frequency of changes in work situation due to cancer and to analyze... more Objective: To investigate the frequency of changes in work situation due to cancer and to analyze the association of physically demanding work, social support from supervisors, colleagues or occupational health services, and disease-related factors, with changing employers due to cancer. Methods: Working-aged patients with breast, testicular or prostate cancer, or lymphoma with a good prognosis between 1997 and 2002 were identified from a hospital or cancer registry in four Nordic countries. The registers provided data on the disease-related factors. Information on changes in work situation, received support, and other work-related factors was collected using a questionnaire (response rate 72%). The frequency of changes in work situation was evaluated among a total of 2030 survivors. Further analyses were carried out among 688 survivors using a multivariable logistic regression model, to investigate factors affecting the risk of changing employers due to cancer. Results: Altogether, 5-10% of cancer survivors had changed employers, occupations or work tasks, 5% had been unemployed, and 9% had retired due to cancer. The physical demands of previous work were the most important reason behind changing employers after cancer. Among women, weak support from supervisors and occupational health personnel increased the risk of changing employers because of cancer. Conclusions: A minority of cancer survivors changed employers, occupations, or work tasks because of cancer. Supervisors' support in the form of lightening physically demanding jobs and taking illness into consideration when planning work tasks, and health-care workers' advice on coping at work may help survivors to maintain their jobs.
Mental disorders among suicide victims who had suffered from cancer were investigated using psych... more Mental disorders among suicide victims who had suffered from cancer were investigated using psychological autopsy data on all suicides in Finland over 1 year. Retrospective DSM-III-R consensus diagnoses were assigned to all 60 cancer suicides and to 60 age-and sex-matched comparison suicides without a cancer history. Depressive syndromes were equally common along cancer suicides (80%) and others (82%). Alcohol dependence and personality disorders were more frequent among noncancer suicides. Major depression and substance abuse were more common among victims with cancer in remission than in terminal stages. Only a small minority of cancer suicides seem to occur in the absence of mental disorders.
We investigated whether a short course in communication skills for physicians would improve the q... more We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a randomized clinical adjuvant trial on breast cancer. In this prospective, case-controlled intervention study, physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course. The quality of informed consent was then evaluated by addressing a standardized questionnaire, QuIC, to trial patients at the three intervention hospitals and at control hospitals. Response rate was 90.0% (n0/288). Of the patients treated by the intervention group, 73% were very satisfied with the information received compared with 56% of those of the control group (p0/0.003). The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls (98% vs. 90%, p0/ 0.004). The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment (91% vs. 97%, p 0/ 0.032). They also understood the main aim of the study better than the patients of the controls (89% vs. 78%, p 0/ 0.030). In conclusion, a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial.
Objecti6e: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausa... more Objecti6e: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. Methods: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n= 54) then started using estradiol as oral tablets (2 mg/day) (n= 44) or as transdermal gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients (n= 34) used only estradiol, orally (2 mg/day) (n= 31) or transdermally (1.5 mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. Results: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9 98.6 to 9.9 9 6.7 (mean 9SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14-24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%
The antitumor activity of cisplatin (cis-diamminedichloroplatinum (II)) is thought to involve bin... more The antitumor activity of cisplatin (cis-diamminedichloroplatinum (II)) is thought to involve binding to cellular protein and nucleic acids (Roberts and Thomson 1979). The purpose of this study was to investigate using atomic absorption spectroscopy (AAS) the correlation between cisplatin dose and Pt concentrations in blood proteins (plasma proteins and hemoglobin) of cancer patients undergoing chemotherapy.
The Journal of Clinical Endocrinology and Metabolism, Apr 1, 1998
Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer.... more Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of breast cancer. Tamoxifen is the most commonly used antiestrogen, but toremifene is gaining in popularity. We compared here the effects of tamoxifen and toremifene on bone metabolism and density in 30 postmenopausal patients with breast cancer, who were randomized to receive tamoxifen (20 mg/day, n ϭ 16) or toremifene (40 mg/day, n ϭ 14) for 1 yr. Biochemical markers of bone resorption [urinary hydroxyproline, serum cross-linked carboxyterminal telopeptide of type I collagen, urinary cross-linked aminoterminal telopeptide of type I collagen (NTx)] and bone formation [serum bone-specific alkaline phosphatase, osteocalcin, and aminoterminal and carboxyterminal propeptide of type I procollagen] were assessed before treatment and at 6 and 12 months of the antiestrogen regimen. Bone mineral density (BMD) in the lumbar spine and proximal femur (neck, trochanter, and Ward's triangle) was measured using dualenergy x-ray absorptiometry before treatment and at 12 months of treatment. Urinary NTx decreased after 6 months' use of tamoxifen (mean fall: 33%) and of toremifene (mean fall: 16%). Use of tamoxifen was associated with a significant decrease in osteocalcin (mean fall: 25%) and aminoterminal propeptide of type I procollagen (mean fall: 22%), whereas toremifene failed to influence these markers. Tamoxifen increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and 5% in Ward's triangle. Toremifene failed to increase BMD at any site measured, and in contrast, a slight trend toward a fall (Ϫ0.3 to Ϫ0.9%) in BMD was seen in patients treated with toremifene. Falls in urinary NTx, from baseline to 6 months, correlated significantly with changes in the lumbar spine BMD (r ϭ Ϫ0.57, P ϭ 0.0002) in the whole patient series. We conclude that tamoxifen (20 mg/day) increases BMD in postmenopausal breast cancer patients, whereas toremifene (40 mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged studies on bone metabolism, comparing these two antiestrogens, are needed; but even now, clinicians should be aware of these differences between tamoxifen and toremifene.
Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamin... more Female rats were subjected to a 70% partial hepatectomy and administered either diethylnitrosamine (10 mg/kg) or the solvent, trioctanoin. After a 2 day recovery from the surgery, the rats were placed on basal diet alone or containing phenobarbital (500 mg/kg diet), mestranol (0.2 mg/kg diet), tamoxifen (250 or 500 mg/kg diet) or toremifene (250, 500 or 750 mg/kg diet) for 6 or 18 months prior to killing. The liver and kidneys were prepared for pathological diagnoses. In addition, sections of liver from the 6 month killing were frozen and serially sectioned. The sections were stained for expression of the placental isozyme of glutathione S-transferase (GST), gamma glutamyl transpeptidase (GGT), canalicular ATPase (ATP) and glucose 6-phosphatase (G6P) and scored by quantitative stereology for number and volume fraction of liver occupied by altered hepatic foci (AHF) with alterations in these markers individually and combined (ANY). Each of the agents increased the volume fraction of liver occupied by AHF when the ANY category was used. Statistical increases in both the GGT-positive and G6P-deficient AHF populations were observed in the spontaneously as well as DEN-initiated groups treated with tamoxifen or toremifene. After 18 months of administration, the highest concentration of tamoxifen increased the incidence of malignant hepatic neoplasms in non-DEN-initiated rats. Toremifene, at the highest tested dose, increased the incidence of hepatocellular carcinomas in the DEN-initiated groups to a level one-third that observed with tamoxifen administration to DEN-initiated rats. Both tamoxifen and toremifene increased the incidence of hypernephromas in previously DEN-initiated rats. While both tamoxifen and toremifene are effective promoting agents for DEN-initiated lesions, tamoxifen is more potent than toremifene in the induction of rat hepatocarcinogenesis.
1397 consecutive suicides were committed in Finland in 1987. 60 (4.3%) of these involved cancer p... more 1397 consecutive suicides were committed in Finland in 1987. 60 (4.3%) of these involved cancer patients, 25 of whom were in remission, 18 in the terminal phase and 17 at other stages of their illness. The background of every case was explored by a structured interview of health care personnel and intimate associates and by examining medical and other case records. The factors connected with and motives for suicide were compared in the two patient groups, the terminally ill and the patients who committed suicide during remission. These groups differed markedly, with the latter having more histories of personal and family mental disorders and suicides among family members. Information which might help clinicians identify suicidal cancer patients was obtained. Withdrawal from social contacts, depression, professed suicidal thoughts and a history of suicide attempt are classical portents of suicide also in cancer patients and should not be ignored. The health care system needs to pay greater heed to the psychological needs of cancer patients. Continuity of the doctor-patient relationship should be guaranteed. Effective symptom control of the terminal patients is very important and could have been achieved in many cases through more competent treatment. Only in a very small minority of cancer patients does suicide seem rational and inevitable.
Objective: To investigate the frequency of changes in work situation due to cancer and to analyze... more Objective: To investigate the frequency of changes in work situation due to cancer and to analyze the association of physically demanding work, social support from supervisors, colleagues or occupational health services, and disease-related factors, with changing employers due to cancer. Methods: Working-aged patients with breast, testicular or prostate cancer, or lymphoma with a good prognosis between 1997 and 2002 were identified from a hospital or cancer registry in four Nordic countries. The registers provided data on the disease-related factors. Information on changes in work situation, received support, and other work-related factors was collected using a questionnaire (response rate 72%). The frequency of changes in work situation was evaluated among a total of 2030 survivors. Further analyses were carried out among 688 survivors using a multivariable logistic regression model, to investigate factors affecting the risk of changing employers due to cancer. Results: Altogether, 5-10% of cancer survivors had changed employers, occupations or work tasks, 5% had been unemployed, and 9% had retired due to cancer. The physical demands of previous work were the most important reason behind changing employers after cancer. Among women, weak support from supervisors and occupational health personnel increased the risk of changing employers because of cancer. Conclusions: A minority of cancer survivors changed employers, occupations, or work tasks because of cancer. Supervisors' support in the form of lightening physically demanding jobs and taking illness into consideration when planning work tasks, and health-care workers' advice on coping at work may help survivors to maintain their jobs.
Mental disorders among suicide victims who had suffered from cancer were investigated using psych... more Mental disorders among suicide victims who had suffered from cancer were investigated using psychological autopsy data on all suicides in Finland over 1 year. Retrospective DSM-III-R consensus diagnoses were assigned to all 60 cancer suicides and to 60 age-and sex-matched comparison suicides without a cancer history. Depressive syndromes were equally common along cancer suicides (80%) and others (82%). Alcohol dependence and personality disorders were more frequent among noncancer suicides. Major depression and substance abuse were more common among victims with cancer in remission than in terminal stages. Only a small minority of cancer suicides seem to occur in the absence of mental disorders.
We investigated whether a short course in communication skills for physicians would improve the q... more We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a randomized clinical adjuvant trial on breast cancer. In this prospective, case-controlled intervention study, physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course. The quality of informed consent was then evaluated by addressing a standardized questionnaire, QuIC, to trial patients at the three intervention hospitals and at control hospitals. Response rate was 90.0% (n0/288). Of the patients treated by the intervention group, 73% were very satisfied with the information received compared with 56% of those of the control group (p0/0.003). The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls (98% vs. 90%, p0/ 0.004). The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment (91% vs. 97%, p 0/ 0.032). They also understood the main aim of the study better than the patients of the controls (89% vs. 78%, p 0/ 0.030). In conclusion, a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial.
Objecti6e: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausa... more Objecti6e: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. Methods: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n= 54) then started using estradiol as oral tablets (2 mg/day) (n= 44) or as transdermal gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients (n= 34) used only estradiol, orally (2 mg/day) (n= 31) or transdermally (1.5 mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. Results: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9 98.6 to 9.9 9 6.7 (mean 9SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14-24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%
The antitumor activity of cisplatin (cis-diamminedichloroplatinum (II)) is thought to involve bin... more The antitumor activity of cisplatin (cis-diamminedichloroplatinum (II)) is thought to involve binding to cellular protein and nucleic acids (Roberts and Thomson 1979). The purpose of this study was to investigate using atomic absorption spectroscopy (AAS) the correlation between cisplatin dose and Pt concentrations in blood proteins (plasma proteins and hemoglobin) of cancer patients undergoing chemotherapy.
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Papers by Päivi Hietanen