Effect of exercise on mobility, balance, and health-related quality of life in osteoporotic women with a history of vertebral fracture: a randomized, controlled trial.

UNLABELLED: The aim of this randomized controlled trial was to evaluate the effect of a 3-month course of exercises on mobility, balance, disease-specific, and generic health-related quality of life (HRQOL) for women with osteoporosis and a history of vertebral fractures. Our results showed that exercises improved their mobility, balance, and HRQOL. INTRODUCTION: The aim was to evaluate the effect of a 3-month course of circuit exercises plus a 3-h lesson on how to cope with osteoporosis on mobility, balance, and the HRQOL for postmenopausal women (60-84 years) with osteoporosis and a history of vertebral fracture. Our hypothesis was that a 3-month course would have a significantly positive effect on the women's mobility and balance as well as on their HRQOL. METHODS: The participants (89) were randomized to an intervention group (IT) or a control group (CT) and assessed at baseline at 3 months and at 12 months with measurement of maximum walking speed (MWS), Timed Up and GO (TUG), Functional Reach (FR), the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis ('QUALEFFO-41') and the General Health Questionnaire (GHQ-20). The sample size was calculated with reference to walking speed (primary outcome), and the statistical approaches used were Student's t test or the chi-square test. RESULTS: At 3 months, better results were registered on the primary outcome, MWS as well as TUG, FR, sum score of GHQ-20, and "QUALEFFO-41: mental function" in the IT compared with the CT. At 12 months, those in the IT had a better result on the primary outcome, MWS as well as TUG, "QUALEFFO-41: total score" "QUALEFFO-41: mental function", "QUALEFFO-41: physical function", and "QULEFFO-41: pain" compared with CT. CONCLUSION: Circuit exercises will improve mobility and health-related quality of life of elderly women with osteoporosis and a history of vertebral fractures.

Pessimism as a predictor of emotional morbidity one year following breast cancer surgery.

The prevalence of and predictive factors for emotional morbidity (measured by the Hospital Anxiety and Depression Scale (HAD)) one year following surgery, with special focus on dispositional optimism/pessimism (measured by the Life Orientation Test (LOT-R), was examined in 165 women, newly diagnosed with breast cancer. Patients characteristics, appraisal of cancer diagnosis, beliefs about treatment efficacy, treatment decision-making participation, coping and emotional morbidity was assessed by self-rating questionnaires. Prevalence of anxiety and depression cases at time of diagnosis was 34 and 12%, respectively, and 26 and 9% after one year. Prevalence of emotional morbidity was significantly enlarged among pessimists at all assessments. Pessimism was the strongest predictor for anxiety (OR: 0.86 C.I. 95% 0.77 - 0.95) and depression (OR: 0.83, C.I. 95% 0.73 - 0.95) one year following breast cancer surgery. Optimists and pessimists differed not only in regard to coping styles, but also in regards to predictors of emotional morbidity. Optimists experiencing anxiety at time of breast cancer diagnosis had about six times higher risk of experiencing anxiety after one year, compared to optimists without preoperative anxiety. For pessimists, the more pessimistic one was about one's overall future the higher risk for developing anxiety following one year of breast cancer surgery. Pessimists, who endorse helpless/hopeless coping style when receiving a diagnosis of breast cancer, had three times greater risk for experiencing depression one year after breast cancer surgery, than pessimists who did not. Health care professionals should therefore provide intervention for pessimists, as well as for patients with high anxiety scores at time of diagnosis.

Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.

PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Detection of isolated tumor cells in BM from breast-cancer patients: significance of anterior and posterior iliac crest aspirations and the number of mononuclear cells analyzed.

BACKGROUND: The aim of this study was to determine the influence and significance of different aspiration sites and the number of mononuclear cells (MNC) analyzed on the frequency of isolated tumor cell (ITC) detection by immunocytochemistry (ICC) in BM aspirates from breast-cancer patients. METHODS: BM aspirates were collected from the two anterior and two posterior crests just prior to primary surgery. The BM was processed separately from the anterior and the posterior crests, and cytospins (2 x 10(6) MNC) were prepared for ICC examination. The remaining cells were pooled, followed by cytospin preparation and ICC analysis (2 x 10(6) MNC/test). In addition, a fraction of the pooled cells were further processed by negative immunomagnetic selection, for enrichment of ITC. Out of 100 patients selected, 97 were further analyzed. RESULTS: The ICC examination from the separate crests revealed 37 positive BMs from the anterior iliac crest and 30 positive from the posterior crest. Twenty-one of the samples were positive at both sides. Five patients had 10 or more ITCs detected. In these, an unequal distribution of ITCs between the sides was observed, but in favor of neither. ICC analysis of 2, 4 and 6 x 10(6) MNC revealed respectively 22, 46 and 52 positive BMs out of the 97 analyzed. These results were correlated to the clinical outcome after a median 43 months follow-up. Thirteen of the patients underwent systemic relapse. Analyzing 2 x 10(6) MNC by ICC, 27.3% of the BM+ patients developed systemic disease, compared with 9.3% of the BM+ patients (P = 0.0056, log rank test). Analyzing 6 x 10(6) MNC reduced the correlation between ITC in BM and clinical outcome. CONCLUSION: No significant difference in the detection rate of ITCs from the anterior and the posterior iliac crests was found, although the distribution of ITCs did show a great variability. Analyzing a higher number of BM cells increased the number of positive BM specimens detected. However, this increased detection rate reduces the prediction by ICC of early systemic relapse.

Logistics of referral, diagnostic assessment and treatment of patients with breast symptoms and signs.

BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.

Do women newly diagnosed with breast cancer and consulting surgeon assess decision-making equally?

This study assesses the perception of the decision-making process of 25 surgeons and 194 patients (aged 21-81 years) who had newly diagnosed breast cancer and had to undergo mastectomy or breast-conserving surgery (BCS). The majority of women wanted to participate in decision-making. When it was medically possible to give a choice between BCS and mastectomy, only 59% of women received a choice. The main reason that 11% of the women went against surgeon's recommendations was fear of cancer recurrence. The most influential factors for women were the surgeon's recommendation, and fear of cancer recurrence. Medical assessment and the cosmetic result were the most influential factors for the surgeons. Female surgeons were more influenced by their assessment of the women's need for security, than male. In conclusion, not all women who are eligible for BCS receive an option. Women and surgeons emphasize influencing factors differently. The surgeon's gender was found to influence recommendation given.

Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics.

UNLABELLED: PURPOSE/EXPERIMENTAL DESIGN: The importance of detection of disseminated isolated tumor cells (ITCs) in bone marrow (BM) is still not settled. BM aspirates from 920 patients with primary breast cancer were analyzed for tumor cells by standardized direct immunocytochemical analysis (ICC) of 2 x 10(6) mononuclear cells (MNCs) using anticytokeratin monoclonal antibody (AE1/AE3). Samples (637) were analyzed by negative immunomagnetic enrichment (IMS) followed by ICC (10 x 10(6) MNCs). Analyses of the primary tumor specimens have been performed, including histomorphology, tumor-node-metastasis (TNM) staging, grading, and immunohistochemical analyses. RESULTS: Of the patients with infiltrating carcinoma, 63% were node negative (N0) and 33%, node positive (N+). The results show the presence of tumor cells in 13.4% of the evaluable patients after direct ICC analysis. The presence of tumor cells correlated to the nodal- and tumor stage, showing BM positivity in 9.9% of the N0 cases and 20.6% in the N+ group (P < 0.0005), 11.2% of the stage T(1) were positive, and 15.0% and 22.6% were positive in the T(2) and T(3/4) groups, respectively (P = 0.013). No correlation between detection of ITC and detection of p53 and cathepsin D expression was found. Vascular invasion and c-erbB2 expression were associated with ITCs in BM (P = 0.045 and P = 0.024, respectively). Node-negative patients with estrogen receptor (ER)+ and/or progesterone receptor (PgR)+ tumors had lower frequency of ITCs than ER-/PgR- (P = 0.004). The use of negative IMS increased the frequency of positive BM by 63% (P < 0.0005). CONCLUSIONS: The direct ICC detection of ITCs in BM correlated with primary tumor stage, nodal stage, vascular invasion, c-erbB2 expression, and ER/PgR status. Analysis of larger BM samples by negative IMS resulted in increased number of ITC-positive patients.

[Breast cancer surgery in Norway 1990-95 illustrated by data from SINTEF United]. / Brystkreftkirurgi i Norge 1990-95 belyst med data fra SINTEF Unimed.

BACKGROUND: Breast-conserving therapy has been shown to be as effective as mastectomy in many cases; hence in many countries more breast cancer patients are offered this type of treatment. This study focuses on the amount and type of surgery used in Norway for breast cancer patients and the possible use of hospital discharge data to evaluate the diffusion of this surgical practice. MATERIAL AND METHODS: Data from the nationwide Register of Hospital Discharges in Norway at SINTEF Unimed for patients operated for breast cancer from 1990 to 1995 were used. RESULTS: 11,041 patients were registered with 11,727 hospital admissions for breast cancer operations from a total of 64 hospitals. The discrepancy in the number of breast cancer patients with the National Cancer Registry was 7%. Breast-conserving surgery was performed in 19.7%. An increase from 17% in 1990 to 21% in 1995 was found, but with variations according to type of hospital, county and age of patients. INTERPRETATION: The percentage of breast conserving surgery is still low in Norway; this indicates that many women are not offered this type of surgery. With some caution, the data from SINTEF Unimed can be used to reflect the clinical practice over time at Norwegian hospitals. Further improvements could be obtained if national identity numbers were added to the database.

Mammography screening in Norway: results from the first screening round in four counties and cost-effectiveness of a modeled nationwide screening.

OBJECTIVE: To evaluate whether the results of the first screening round in the Norwegian Breast Cancer Screening Program predict future mortality reduction and to explore the cost-effectiveness of the program. METHODS: The results of surrogate measures were calculated and compared with the targets. A cost-effectiveness analysis was performed assuming a nationwide program starting in 1996 with an attendance rate of 80% and a mortality reduction of 30%. RESULTS: The attendance rate was 79.5% and the detection rate was 0.67%. The proportion of invasive tumors smaller than 15 mm was 53.1%, and 21.7% of the patients who underwent axillary surgery had lymphatic metastasis. The C/E ratios were found to be 3750 US dollars (USD) per year of life saved and 86,045 USD per life saved. CONCLUSION: The results of the first screening round will lead to a mortality reduction of at least 30%. The cost-effectiveness analysis shows that it is possible to run a highly cost-efficient screening program in Norway.

Screening for breast cancer is associated with a low degree of psychological distress.

Psychological distress was measured among women on the day of recall after mammography in an official screening programme, and 4 weeks after the diagnosis was given. The Hospital Anxiety and Depression Scale (HADS) and a questionnaire to assess reactions to the examination were completed by 213 (97%) women aged 50-69 years. Among those without cancer, there were 45 (24.3%) who were anxiety cases and eight (4.3%) depression cases (HADS) on the day of recall mammography and 12 (7.3%) and three (1.8%) respectively after 4 weeks (P<0.001). Among those with cancer, the corresponding figures were seven (28.0%) and one (4.8%) before and six (24.0%) and three (12%) after screening (n.s.). A total of 194 (97%) women were definitely satisfied with the screening programme, and 195 (98%) would recommend others to participate. In conclusion, recall after mammography is associated with transiently increased levels of anxiety and depression in women without cancer. For those with cancer, the psychological distress continues. The women were almost unanimously content with participating in the screening programme.

Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients.

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.

[Psychological, social and economic situation of women surgically treated for cancer]. / Kreftopererte kvinners psykiske, sosiale og økonomiske forhold.

INTRODUCTION: As part of an international effort, a study of the psychosocial condition of women with cancer in Norway was performed in 1997. MATERIAL AND METHODS: 851 women with breast or gynaecological cancer in 27 Norwegian hospitals were asked to fill in a multi-choice questionnaire. RESULTS: 76% of the breast cancers were detected by the women themselves, 19% by mammography and 11% by clinical examination. Similar numbers for gynaecological cancer were 59% by the women and 41% by the doctors (13% screening smear). 25% of the women were informed about the cancer diagnosis by telephone and 9% by letter. 87% were satisfied with treatment and care, 7% dissatisfied. 62% were satisfied with the availability of doctors, 20% not. In 47% of the breast cases, therapy alternatives were discussed with the patients. In 23% of gynaecological, 50% of breast, and 72% of gynaecological cancer, patients had no wish to participate in the decision. 94 of a total of 850 patients (11%) experienced financial problems after the diagnosis had been established. More than 90% of the women had a better or unchanged relation to their partner, family and friends after treatment. However, 30% of the breast and 14% of the gynaecological cancer patients had problems with their body image, and 16% and 15% felt they were less sexually attractive. 89% felt their partner coped well with the situation, 9% had problems and only 2% lost their partner. 32% of the patients had used alternative medicine, 44% of those with recurrence and 28% under primary treatment. INTERPRETATION: Women operated for breast and gynaecological cancer face a variety of psychosocial and financial problems.

Screening breast cancer patients for Norwegian ATM mutations.

483 Norwegian breast cancer patients were screened for six different ataxia telangiectasia mutated (ATM) mutations previously found to account for 83% of the disease alleles in Norwegian ataxia telangiectasia (AT) patients. Only one carrier was found. These results provide no evidence in favour of an excess risk of breast cancer associated with heterozygosity for classical AT mutations, but remain consistent with a maximum 2.4-fold increased risk.

[Diagnostic and therapeutic localized breast biopsy]. / Diagnostisk og terapeutisk merkebiopsi i mammae.

Preoperative localized mammary biopsy has been used as a diagnostic tool since before 1983 in the Breast Clinic, Ullevål Hospital. The great majority of procedures have been performed in the outpatient clinic with use of local anesthesia. Since 1988 all activity has been registered prospectively in a database. We discuss the use of the procedure and the results obtained during the period 1983-95. In the later part of the observed period, the use of the procedure as a diagnostic tool has been less frequent, but it has been increasingly used as a tool to identify the pathologic process when performing breast-conserving surgery. Surveillance of the malign-benign ratio is an important parameter in the quality assurance of the procedure. The malign-benign ratio has been greater than 0.3 during the period of observation. Continuous registration of procedure-related parameters is necessary for documentation of the results.

Ductal carcinoma in situ of the breast--a review of diagnosis, treatment and outcome in a hospital-based Norwegian series.

Between 1980 and 1994, 71 women with histologically proven ductal carcinoma in situ (DCIS) were diagnosed at Ullevål Hospital; bilateral tumours were found in two patients. Surgical treatment was mastectomy (42 lesions) or local excision (31 lesions). Median follow-up time was 7.2 years. Ten patients experienced a local recurrence, seven of which were invasive carcinomas. The actuarial 5-year local recurrence rate was 22% after local excision. A multivariate analysis found that tumour size was the only factor that predicted local recurrence after local excision. An analysis of relative survival in a nation-wide material of 832 DCIS patients in the period 1980 to 1994 demonstrates that relative survival after a DCIS diagnosis is almost 100%, irrespective of surgical treatment of the initial lesion.

Genetic variants of CYP19 (aromatase) and breast cancer risk.

The effect of a SNP in exon 10 of CYP19 on tumor mRNA levels and splice variants were studied and correlated with clinical parameters and risk of breast cancer. In the vast majority of breast cancers, the estrogen levels modulate the tumor growth and depend on the activity of CYP19. Patients (n=481) and controls (n=236) were genotyped by T-tracks in a single sequencing reaction (SSR). The frequency of TT genotypes was significantly higher in patients versus controls (P=0.007) particularly among those with stage III and IV disease (P=0.004) and with tumors larger than 5 cm (P=0.001). A significant association between presence of the T allele and the level of aromatase mRNA in the tumors was observed (P=0.018), as well as with a switch from adipose promoter to ovary promoter (P=0. 004). Previously, we reported a rare polymorphic allele of CYP19 (repeat (TTTA)12) to be significantly more frequent in breast cancer patients than in controls. Here we describe another polymorphism, a C - T substitution in exon 10 of the CYP19 gene which is in strong linkage disequilibrium with the (TTTA)n polymorphism but with higher frequency of the variant allele. Our data suggest that the T-allele of the CYP19 gene is associated with a 'high activity' phenotype. Oncogene (2000) 19, 1329 - 1333.

[Cost-effectiveness of mammography screening in Norway]. / Samfunnsøkonomisk lønnsomhet av mammografiscreening i Norge.

Since January 1996, mammography screening every second year has been offered to women aged 50 to 69 in four counties in Norway. As an input to the evaluation of the programme, medical authorities commissioned an analysis of the cost-efficacy of screening. The results are presented in this paper. This study of the screening in the City of Oslo is based on registration of time used on various procedure, data for all procedure performed, and financial accounting data. The result have been recalculated for a simulated nation-wide project. Only costs up to the time of diagnosis (malignant/benign) have been included. The total cost of the Oslo programme 1996/97 was NOK 12.1 m (USD 1.6 m). Cost per women examined was NOK 395 and per cancer detected NOK 57,639. Cost per life saved was estimated at NOK 680,000, per year-of-life saved NOK 30,000. Based on accounting data only, comparisons could be made between counties. Costs in other counties were between 39 and 73% higher than in Oslo. Using an estimate of a 40% higher costs nation-wide, we find that the total cost of one year of nation-wide (population 4.5 m) screening would amount to NOK 83 m, cost per life saved to NOK 950,000, and per year-of-life saved to NOK 41,000. Estimated cost per life saved by traffic safety measures has been NOK 10 m. On this basis, mammography screening in Norway seems to be a highly cost-effective measure.

[A prospective registration of diagnosis and treatment of breast tumors at the Ulleval hospital 1988-1995]. / En prospektiv registrering av diagnostikk og behandling av tumor mammae ved Ullevål sykehus 1988-95.

During the years 1988 to 1995, all diagnostic and therapeutic activities in the Breast Clinic, Ullevål Hospital, Oslo, Norway were registered prospectively. This paper presents the results from the registration. Of 4,436 new referrals, 1,169 had infiltrating mammary carcinoma and 63 ductal carcinoma in situ. 13.6% of those with breast carcinoma and 12.3% of those with benign breast disease had a first degree relative with breast cancer. The use of diagnostic biopsies for palpable and nonpalpable lesions decreased significantly through the period, from 155/112 in 1988 to 65/78 in 1995. For palpable lesions, the malign/benign ratio decreased from 0.82 in 1988 to 0.54 in 1995 while it improved from 0.43 to 0.88 for marked biopsies for nonpalpable lesions. Excluding those with mammographically and/or cytologically suspicious lesions from those who had a biopsy for a palpable lesion, we found that only seven out of 101 had cancer (ratio 0.07). Radical surgery was done in 790 cases with cytology as the only pre- and peroperative cancer verification. Three of them had a false positive cytology, as cancer was not found in the breast. One patient had metastasis later confirming that a cancer had been present; thus we had two false positive cytologies (2.5 per thousand). More than six axillary lymph nodes have to be examined in order to avoid false negative axillary status. In 1988 we had 41% with less than six nodes examined. This improved to 15% in 1995. Breast preserving therapy increased throughout the period from 4.1% in 1988 to 29.4% in 1995. Tumor size (pTI around 40%) and node positivity (35%) was fairly constant. In our opinion, a continuous prospective registration of the activity in a breast diagnostic centre is essential in order to improve and maintain service quality. The decision made by the Norwegian parliament in 1998 to introduce nation-wide mammography screening may be used to institute such continuous prospective registrations in all centres involved in the screening.

[Follow-up of women surgically treated for breast cancer]. / Etterkontroll av kvinner operert for cancer mammae.

From May 1997, all breast cancer patients who had undergone ablatio were asked to contact their general practitioner for follow-up after six months. Evaluation of the method used was performed by means of a questionnaire sent to 148 women. At the same time report forms returned from the general practitioners were registered. 132 women returned the questionnaires (89%). Only seven women (5%) had not contacted their general practitioner. 117 women (89%) had been or were summoned to their general practitioner. This shows that general practitioners take responsibility for follow-up when the women get in touch. We received 52 (58%) report forms from the general practitioners. The reason for this low response rate among the general practitioners might be inadequate motivation.